coe in livestock diseases and human health 2001-2005

Center of Excellencein Livestock Diseasesand Human HealthFive-Year Report 2001-2005

Center of Excellence in Livestock Diseases and Human Health A Tennessee Higher Education Commission Accomplished Center of Excellence Annual Report 2001 - 2005

The University of Tennessee does not discriminate on the basis of race, sex, color, religion, national origin, age, disability, or veteran status in the provision of educational programs and services or employment opportunities and benefits. This policy extends to both employment by and admission to the University. ▪ The University does not discriminate on the basis of race, sex, or disability in the education programs and activities pursuant to the requirements of Title VI of the Civil Rights Act of 1964, Title IX of the Education Amendments of 1972, Section 504 of the Rehabilitation Act of 1973, and the Americans with Disabilities Act (ADA) of 1990. ▪ Inquiries and charges of violation concerning Title VI, Title IX, Section 504, ADA, The Age Discrimination in Employment Act (ADEA), or any of the other referenced policies should be directed to the Office of Equity and Diversity, 1840 Melrose Avenue, Knoxville, TN 37996-3560; telephone (865) 974-2498 (TTY available). Requests for accommodation of a disability should be directed to the ADA Coordinator at the Office of Human Resources Management; 600 Henley Street, Knoxville, TN 37996-4125.

Center of Excellence in Livestock Diseases and Human Health A Tennessee Higher Education Commission Accomplished Center of Excellence Annual Report 2001 - 2005

Editor Jada Huskey Photography Greg Hirshoren Cover Design Misty Bailey Anik Vasington

We are pleased to present the 2001-2005 five year report for the Center of Excellence in Livestock Diseases and Human Health. Along with benchmark data and success stories for fiscal years 2001-2005, this report includes highlights of faculty research projects funded by the Center in 2005.

During 2001-2005, the Center supported the research efforts of 30 different faculty who were engaged in research that ultimately will benefit the citizens of Tennessee and the nation and impact the economy at both the state and the national level. Center faculty have made significant advancements in cancer biology, molecular physiopathology, host defense, and disease transmission. Center faculty also have made significant advancements in the prevention and treatment of infectious and non-infectious livestock diseases, which affect agricultural productivity.

Productivity among Center faculty has been outstanding during 2001-2005. External funding increased from $12,770,303 in 2001 to $19,735,365 in 2005; research expenditures increased from $2,579,219 in 2001 to $4,062,712 in 2005. The five-year average return on the State's investment in the Center as the ratio of research expenditures to the State's appropriation is 6.0:1. Center faculty continue to garner national and international recognition for their research and scholarship. During 2001-2005, Center faculty published 416 peer-reviewed articles and gave 234 invited presentations at national and international meetings.

We are proud of the progress made by Center faculty and we hope you enjoy this summary presentation of Center activities and accomplishments.

Michael J. Blackwell, Dean Robert N. Moore, Director

Dr. Michael J. Blackwell and Dr. Robert N. Moore

The University of Tennessee ▪ College of Veterinary Medicine ▪ Center of Excellence in Livestock Diseases and Human Health 2407 River Drive, A102 ▪ Knoxville, TN 37996-4550

http://www.vet.utk.edu

Message from the Center of Excellence

FY 2005 Summary of Accomplishments

Benchmark Fiscal Year 2005

(18 Faculty in Center)

Fiscal Year 2004

(17 Faculty in Center)

Publications

-Refereed Articles 92 106

-Books or Book Chapters 8 4

-Proceedings

27 35

Abstracts

37 60

Presentations

-National 13 35

-International

14 31

External Funding

$19,735,365 $18,249,519

Research Expenditures

$4,062,244 $3,392,244

Return on Investment 7.8:1 6.8:1

Table of Contents

Program Report 1

Introduction 1 Research Funding 1 Equipment 2 Student Research 2 Culture for Discovery 3 Infrastructure 4 Personnel 4 Dissemination of Research 4 Accomplishments 4 Research Expenditures 5 Research Funded Externally - Summary 6 Five-Year Benchmark Data 7 Success Stories 2001-2005 9 Future Plans 12 Faculty Reports 13

Animal Models and Comparative Medicine Dr. Hildegard Schuller 14 Dr. Hwa-Chain Robert Wang 15 Dr. Howard Plummer, III 16 Dr. Patricia Tithof 17 Dr. Seung Joon Baek 18 Dr. Mei-Zhen Cui 19 Dr. Xuemin Xu 20 Dr. Steve Kania 21 Dr. Michael Fry 22 Dr. Michael McEntee 23 Mechanisms of Disease, Pathogenesis, and Immunity Dr. Barry Rouse 24 Dr. Pamela L.C. Small 25 Dr. David Brian 26 Dr. Stephen Oliver 27 Dr. Gina Pighetti 28 Dr. James Godkin 29 Dr. Frank Andrews 30 Dr. Terry Schultz 31 Publications and Presentations 32 Research Funded Externally - Detail 51 Budget Schedule 7 55

Program Report

Introduction

The Center was created in 1984 to promote interdisciplinary activities designed to improve the quality of human life through better animal health; expand livestock disease research capabilities in the College of Veterinary Medicine (CVM) and the Institute of Agriculture; identify and characterize animal diseases that are similar to human disease; and develop new strategies for the diagnosis, treatment, and prevention of disease.

Since 1984, the Center has developed successful programs that impact the understanding, treatment, and prevention of livestock and human diseases. These programs predominately focus on molecular and cellular approaches to research in infectious diseases; toxicology; host defense; molecular genetics; and carcinogenesis.

The Center has developed investigative strengths along innovative, sophisticated, and contemporary lines in two general areas:

1) Animal Models and Comparative Medicine 2) Mechanisms of Disease, Pathogenesis, and Immunity

These areas are each highly interrelated, and the Center plays a critical role in developing these focused areas of strength in both the College of Veterinary Medicine and the College of Agricultural Sciences and Natural Resources.

Research Funding

The Center of Excellence in Livestock Diseases and Human Health supports investigators and promotes research through a variety of mechanisms. Although it is not a primary source of research funding, the Center facilitates established investigator's efforts to maintain and expand their research programs and promotes new investigator’s potential to develop competitive research programs.

The Research and Graduate Programs Advisory Committee reviews funding requests based on three main criteria: scientific merit, potential to lead to extramural funding, and relevance to the Center's objectives.

Center faculty consist of senior members who have research interests in line with Center objectives and have a strong history of securing external funding using Center funds. Junior members are those who have received seed money or bridge funding, or new faculty who have received start-up funds. Junior members are expected to secure external funding within two years; members who fail to secure such funding will be placed on probation for one year. If at the end of the probationary period external funding has not been secured, the member will be dismissed from the Center.

The Center awarded $402,200 in seed money and start-up funds to 18 faculty in 2005

Program Report

Equipment

The Center promotes the research infrastructure of both the CVM and the Institute of Agriculture through the purchase and maintenance of essential research equipment. The Research and Graduate Programs Advisory Committee reviews equipment requests based on three criteria: justification of need, current availability of equipment, and number of investigators who may benefit. During fiscal year 2005 the Committee approved 2 pieces of equipment totaling $50,000. These equipment grants benefited several investigators, including Dr. Hwa-Chain Wang, Dr. Hildegard Schuller, and Dr. Howard Plummer.

Student Research

In an effort to foster interest in careers in biomedical research, the Center provides opportunities for veterinary students to perform research in laboratories within the College of Veterinary Medicine during the summer.

This program has been quite successful. In fact, each year several students often re-apply for a second summer research opportunity. Students report that the summer program enhances their educational experience and helps them to identify and to clarify career goals.

In addition to laboratory research, the students attend weekly professional development seminars, during which guest speakers address topics such as career opportunities in research, research study design, ethics in research, compliance issues in lab animal care, scientific writing, and the grant proposal process.

Near the end of the 10-week program, the students present their research findings to their colleagues and to CVM faculty. Several students also have presented their work at national scientific meetings, and numerous manuscripts detailing the student’s work have been submitted for publication in refereed journals. Over the past seven years approximately 48 manuscripts, several with students from this program as senior authors, were published in refereed journals.

In order to maximize student participation, the program is open to both Center and non-Center faculty. During fiscal year 2005, COE faculty participation in the program included Drs. Baek, Schultz, and Tithof. The Center will continue to encourage participation of Center faculty.

Dr. Claudia Kirk, coordinator of the summer research program, has received external funding to enhance this program.

Dr. Claudia Kirk, program coordinator, received funding from the Merck-Merial Veterinary Scholars Program to enhance the summer research program, which funded 20 first- and second-year students in FY 2005

Program Report

Culture for Discovery

In conjunction with the CVM graduate program in Comparative and Experimental Medicine, the Graduate School of Medicine, and the departments of Animal Science and Microbiology, the Center sponsored several invited speakers through two seminar series: Mechanisms of Disease and Microbial Pathogenesis. These well-attended seminars foster a culture for discovery by stimulating discussion and interaction among students and faculty. In addition, the seminars provide the potential for establishing productive external collaborations for faculty.

Speaker Topic

Manuel Amieva, M.D. Stanford University

Helicobacter pylori

Guy M. Chisholm, Ph.D. The Cleveland Clinic Foundation

The Role of Stat1 Signaling in Lipoprotein Engorgement by Macrophages: Implications for Atherosclerosis

Channing J. Der, Ph.D. UNC, Chapel Hill

Targeting Ras for Cancer Treatment

Stanley E. D'Souza, Ph.D. University of Louisville

Regulation of Vascular Function by an Adhesion Receptor, ICAM-1

Thomas E. Eling, Ph.D. NIEHS

Cyclooxygenase and Lipoxygenase in Cancer

Vincent Fischetti, Ph.D. Rockefeller Institute

Streptococcus spp.

Fadlo Khuri, M.D. Emory University

Molecularly Targeted Approaches to the Chemoprevention of Cancer

J. Thomas Parsons, Ph.D. University of Virginia

Cell Adhesion, Migration and Cancer

Sue Priola, Ph.D. NIAID, NIH, Rocky Mtn. Laboratories

Prions

Kaladhar B. Reddy, Ph.D. Wayne State University

Breast Cancer Endocrine Resistance: How Growth Factor Signaling and Estrogen Receptor Modulate Response

Albert B. Reynolds, Ph.D. Vanderbilt University

In Vitro and In Vivo Regulation of E-Cadherin by p120-Catenin: Evidence of a Tumor Suppressor Role

Gary Schoolnik, M.D. Stanford University

DNA Micro-Arrays, Mycobacterium tuberculosis

June Scott, Ph.D. Emory University

Streptococcus pyogenes

Neena Singh, M.D., Ph.D. Case Western Reserve University

The Biology and Pathophysiology of Human Prion Disorders

Man-Sun Sy, Ph.D. Case Western Reserve University

The Good, the Bad, and the Ugly Prion

Dave White, Ph.D. FDA Center for Veterinary Medicine

Antimicrobial Resistance

Huaxi Xu, Ph.D. The Burnham Institute

Proteolytic Processing and Intracellular Trafficking of Beta Amyloid Precursor Protein

Program Report

Infrastructure

In support of the CVM's research enterprise, the Center provides a skilled cell sorter technician for flow cytometry lab; the maintenance contract on the flow cytometer; supplies for the cell sorter; training, as required, for the cell sorter; and a secure BSL2 facility. In addition, the Center is developing a tissue culture core facility.

Personnel

Dr. Robert N. Moore, Professor and Associate Dean for Research and Graduate Studies continues as Director of the Center. There have been no changes in personnel.

Dissemination of Research

CVM distributes two quarterly newsletters, Veterinary News and Volunteer Vet, and an annual magazine, Veterinary Vision to keep the public informed of research accomplishments. These publications, which carry features concerning on-going research activities and the results of concluded research studies, are written for a general audience. The CVM website provides an overview of the types of research conducted by CVM and COE faculty. CVM also issues press releases to state, regional, and national media resulting in numerous television and print features, many of which relate directly to research conducted through the Center. In addition, faculty are encouraged to share their research by speaking to professional groups, community groups, and civic groups.

Accomplishments - FY 2005

Center faculty continue to make excellent progress in on-going projects, gaining national and international recognition for their expertise and accomplishments. Details of current faculty research are provided in the Faculty Reports section. Center accomplishments for the year 2004-2005 were excellent in terms of benchmarks and extramural funding base.

The 18 Center faculty averaged approximately 5 refereed publications (92 total), and 1.5 invited presentations (27 total) at prestigious national and international meetings. See Publications and Presentations for details.

The return on the State's investment in the Center as the ratio of expenditures from extramural funding to Center appropriation was 7.8:1. Extramural funding totaled $19,735,365 increasing more than $1.4 million this year. The total funding includes new multi-year awards for Drs. Baek, Oliver, Schuller, Schultz, Small, and Wang totaling $1,485,846. Research expenditures increased 19.8% from $3,392,244 in 2004 to $4,062,712 in 2005. See Research Expenditures and Research Funded Externally for FY 2005 data summary.

► External funding totaled $19,735,635

► New grants totaled $1,485,846

► Return on investment 7.8:1

Research Expenditures FY 2005

Seung Baek Howard Plummer, III Federal $127,538 Federal $158,661 Industry 0 Industry 0 Foundation/Private 0 Foundation/Private 0

Total $127,538 Total $158,661 David Brian Barry Rouse Federal $367,686 Federal $833,207 Industry 0 Industry 0 Foundation/Private 0 Foundation/Private 0

Total $367,686 Total $833,207 Mei-Zhen Cui Hildegard Schuller Federal $247,812 Federal $837,693 Industry $173,365 Industry 0 Foundation/Private $75,622 Foundation/private 0

Total $496,799 Total $837,693 Stephen Kania Terry Schultz Federal 0 Federal $172,623 Industry $42,772 Industry 0 Foundation/Private 0 Foundation/private 0

Total $42,772 Total $172,623 Michael McEntee Pamela L.C. Small Federal $99,488 Federal $270,437 Industry 0 Industry 0 Foundation/Private 0 Foundation/Private $17,506

Total $99,488 Total $287,943 Stephen Oliver Hwa-Chain Wang Federal $39,362 Federal 0 Industry 0 Industry 0 Foundation/Private $76,092 Foundation/Private $210,344

Total $115,454 Total $210,344 Gina Pighetti Xuemin Xu Federal $11,714 Federal $292,439 Industry 0 Industry 0 Foundation/Private $8,351 Foundation/Private 0

Total $20,065 Total $292,439

The return on the State's investment in the Center as the ratio of expenditures from external funding to Center appropriation is 7.8:1

Total Research Expenditures $4,062,712

State Appropriation $ 520,380

Research Funded Externally FY 2005

Seung Baek Howard Plummer, III Federal $666,452 Federal 0 Industry 0 Industry $752,989 Foundation/Private 0 Foundation/Private 0

Total $666,452 Total $752,989 David Brian Barry Rouse Federal $1,742,401 Federal $4,859,710 Industry 0 Industry 0 Foundation/Private 0 Foundation/Private 0

Total $1,742,401 Total $4,859,710 Mei-Zhen Cui Hildegard Schuller Federal $1,002,400 Federal $3,350,726 Industry $647,397 Industry 0 Foundation/Private $154,000 Foundation/Private 0

Total $1,803,797 Total $3,350,726 Stephen Kania Terry Schultz Federal 0 Federal $2,022,662 Industry $50,000 Industry 0 Foundation/Private 0 Foundation/Private 0

Total $50,000 Total $2,022,662 Michael McEntee Pamela L.C. Small Federal $485,024 Federal $1,194,750 Industry 0 Industry 0 Foundation/Private 0 Foundation/private $41,570

Total $485,024 Total $1,236,320 Stephen Oliver Hwa-Chain Wang Federal $341,879 Federal $100,000 Industry 0 Industry $659,320 Foundation/Private $262,177 Foundation/Private 0

Total $604,056 Total $759,320 Gina Pighetti Xuemin Xu Federal $65,011 Federal $1,282,500 Industry $54,397 Industry 0 Foundation/Private 0 Foundation/Private 0

Total $119,408 Total $1,282,500

Federal $17,113,515 Industry

$2,164,103

Private/Foundation $457,747

Total Center-related external funding increased by 8% in FY05 due to significant new grants and contracts awarded to Center faculty

$19,735,365 Total External Funding

Five-Year Benchmark Data

FY 2001 - 2005

Productivity among Center faculty has been outstanding during the last five-year period. From 2001 to 2005, Center faculty published 416 articles in peer-reviewed journals and gave 234 invited presentations at national and international meetings. In addition, total external funding increased from $12,760,303 in 2001 to $19,735,365 in 2005. Funding from federal sources increased from $9,365,068 in 2001 to $17,113,115 in 2005. Further, research expenditures increased from $2,579,219 in 2001 to $4,062,712 in 2005. The five-year average return on the State’s investment in the Center as the ratio of research expenditures to the State’s appropriation is 6.0:1. For comparison, benchmark data from 2001 - 2005 are summarized in the tables and charts that follow.

2001 - 2005 Benchmark Summary

► Average refereed articles per faculty = 5.13

► External funding increased 55%

► Federal funding increased 83%

► Expenditures increased 58%

► Average ROI = 6.0:1

Year Faculty Articles Books and Chapters

Proceedings Abstracts Presentations

National International 2001 13 45 2 27 14 20 28

2002 14 57 2 16 30 10 33

2003 20 116 11 17 70 24 26

2004 17 106 4 35 60 35 31

2005 18 92 8 27 37 13 14

Totals 416 27 122 211 102 132

Publications and Presentations 2001 - 2005

2001 2002 2003 2004 2005

$12.7 $11.3

$16.1 $18.2

$19.7

Milli

ons

of D

olla

rs

External Funding by Fiscal Year

Five-Year Benchmark Data

2001 2002 2003 2004 2005

$9.4 $9.9

$13.9 $15.2

$17.1

Milli

ons

of D

olla

rs

Federal Funding 2001 - 2005

Milli

ons

of D

olla

rs

Research Expenditures 2001 - 2005

2001 2002 2003 2004 2005

$2.6 $2.4

$3.1 $3.4

$4.0

Year Faculty State Appropriation Research Expenditures Return on Investment

2001 13 $530,500 $2,579,219 4.8:1

2002 14 $508,500 $2,444,578 4.8:1

2003 20 $516,000 $3,156,469 6.1:1

2004 17 $495,600 $3,392,469 6.8:1

2005 18 $520,380 $4,062,712 7.8:1

Average Return on Investment 6.0:1

Return on Investment as Ratio of Expenditures to State Appropriation 2001 - 2005

Success Stories 2001-2005

Center faculty continue to advance the knowledge in research areas that will benefit the citizens of Tennessee and the nation and impact the economies of the state and the nation. Published papers, patent applications and external funding leveraged by Center monies are important measures of the Center's success. Included below are success stories selected from the 2001-2005 reporting period:

Seung Joon Baek (04-05) identified a novel protein that appears to play a pivotal role in mediating the chemopreventive effects of several anti-cancer compounds, including certain phytochemical compounds found in fruits and vegetables. This newly identified protein stimulates programmed cell death in colon cancer cell lines and in other cancer cell lines as well. Results from Dr. Baek's research could lead to the development of new drugs for cancer treatment and to the development of dietary supplements designed to reduce the risk for cancer; 19 refereed publications.

David Brian (01-05) was at the forefront of the international scientific community's effort to understand severe acute respiratory syndrome, or SARS, a member of the coronavirus family. Dr. Brian discovered a small genetic variant of the bovine coronavirus that replicates in the presence of 'normal' virus. This minigenome is being experimentally engineered to carry many kinds of potential antiviral molecules into cells. In theory, such a novel therapeutic approach would cure a virus-infected cell without killing it; 22 refereed publications.

Mei-Zhen Cui (01-05) found that lysophosphatidic acid (LPA), a component of oxidized low density lipoprotein, markedly increases tissue factor activity, tissue factor protein, and tissue factor messenger RNA in smooth muscle cells, one of three major resident cell types in atherosclerotic lesions. Results from Dr. Cui's studies could lead to new therapeutic targets for treatment and prevention of atherosclerosis; 11 refereed publications.

Stephen Oliver (01-05) discovered fundamentally important information that is critical for controlling the heterogeneous organisms that cause mastitis in dairy cows. In Tennessee alone, losses due to mastitis exceed $25 million annually. Results from Dr. Oliver's research will enable dairy producers to enhance the quantity and quality of milk produced and thus reduce the economic impact of mastitis; 53 refereed publications.

Gina Pighetti (04-05) discovered a marker within a gene that identifies cattle more susceptible to mastitis, the most costly disease affecting dairy producers in Tennessee, the U.S. and throughout the world. This particular gene encodes a receptor for interluekin-8, which is a key regulator of innate immune responses. Dr. Pighetti's work could lead to a means of therapeutically boosting the immune response; 4 refereed publications.

Howard Plummer (02-05) found a functional link between the beta-adrenergic receptor pathway and the G-protein inwardly rectifying potassium channel (GIRK1) in breast cancer cell lines, and the two pathways are involved in regulating the growth of these cancer cells. Modulation of GIRK channels may be an important tool in diagnosis or treatment of breast cancers; 13 refereed publications.


Barry Rouse (01-05) continues to garner international attention for his research on ocular inflammatory disease caused by herpes simplex virus and for the development for a vaccine against herpes. Dr. Rouse recently reported, for the first time, that a particular heat shock protein-peptide system can be used to induce helper T cell and antibody responses. Results from Dr. Rouse's research could lead to the development of novel strategies for the prevention of viral diseases in humans and animals; 64 refereed publications.

Hildegard Schuller (01-05) found evidence that suggests some widely advertised chemopreventive agents, such as green tea and beta carotene, may inhibit cell growth in lung cancer cells of one lineage, while promoting cell growth in lung cancer cells of another lineage. Dr. Schuller is also working with Dr. George Kabalka, Department of Chemistry, to develop novel imaging agents that selectively bind with high affinity to identified receptors, which will allow physicians to detect, using positron emission tomography, the presence of cancers, cardiovascular diseases and neurodegenerative diseases. Based on results of their collaborative research, Dr. Schuller and Dr. Kabalka have two patent applications pending; 28 refereed publications.

Terry Schultz (01-05) and co-investigators Dr. Neal Stewart, Tennessee Agricultural Experiment Station, and Dr. Gary Sayler, Center for Environmental Biotechnology, are developing a biosurveillance web that could be used to detect dangerous chemicals or biological agents in areas of troop deployment. Biosurveillance, Agricultural and Environmental Security: A Coordinated, Innovative Initiative is a $2 million project recently funded by the Department of Defense. Using model compounds, Dr. Schultz is developing a database of gene expression profiles that could be used to predict the hazards of chemicals. Drs. Sayler and Stewart will be adapting Sayler's patented biosensor technology for use in plants and algae to detect harmful bacteria, which could be then monitored remotely to determine the toxin and the concentration level before troops are deployed to the area; 59 refereed publications.

Pamela Small (02-05) isolated and characterized a polyketide-derived macrolide toxin (mycolactone) from Mycobacterium ulcerans, the causative agent of Buruli Ulcer, a flesh-eating skin disease found on several continents. Dr. Small has shown that mycolactone is responsible for the massive tissue damage caused by Buruli ulcer, which is a severe emerging infectious disease in West Africa; 26 refereed publications; 1 patent application.

C.A. Speer (03) lead a team of researchers who developed a new diagnostic test to help farmers reduce Johne's disease, a contagious, chronic wasting disease that causes dairy cows to stop producing milk. Johne's disease affects 22 percent of all dairy herds, resulting in annual economic losses of $200 million to the dairy industry in the United States. The new test is inexpensive and has diagnostic sensitivity and specificity higher than 95 percent. The test also can detect Johne's in young animals before they become contagious and spread the disease. Based on this discovery, two patent applications have been filed and a licensing agreement has been made with a veterinary diagnostic company; 5 refereed publications.


Patricia Tithof (01-05) reported novel findings concerning the effects of specific components of cigarette smoke on endothelial cell function and these findings suggest a novel mechanism by which cigarette smoke augments atherosclerosis. Results from Dr. Tithof's studies may lead to the development of effective measures for preventing cardiovascular complications in smokers; 18 refereed publications.

Hwa-Chain Wang (01-05) has identified a family of novel enzymes that are activated in normal resting cells, in quiescent cells, or in cancerous cells undergoing programmed cell death as a result of a variety of physiological, chemical or physical stresses. Dr. Wang also found that ras-related pancreatic cancer cells are susceptible to FR901228, an agent currently under study for the treatment of cancer. Dr. Wang has identified the roles of three signaling pathways in the FR901228-induced apoptosis of cells undergoing Ras-induced cellular transformation. Results from Dr. Wang's research could lead to the development of agents that prevent cancer by interfering with the biological processes underlying the development of cancer; 11 refereed publications.

Xuemin Xu (01-05) and his group recently discovered a new, longer species of beta amyloid peptide. Beta amyloid is a toxic protein believed to contribute to the development of Alzheimer's disease. This significant discovery provides important insight into the mechanism by which beta amyloid is produced during the gamma-secretase-mediated processing of APP. Given that the longer beta amyloid peptides are more pathogenic than the shorter ones, Dr. Xu's discovery could lead to new targets for the development of methods of preventing and treating Alzheimer's disease, especially those aimed at the design of gamma-secretase inhibitors; 17 refereed publications.

Center faculty featured in these Success Stories used Center monies to generate preliminary data vital to the success of grant proposals funded by the following sponsors:

Federal Industry Private/Foundation

Department of Defense Merial, Inc. American Heart Association

Department of Energy Pfizer Water Environmental Research Foundation

Environmental Protection Agency Pharmacia World Health Organization

National Institutes of Health Philip Morris, Inc.

National Science Foundation Smith-Kline

U.S. Army Sporicidin International

U.S. Department of Agriculture

UT-Battelle

Future Plans

The Center will continue to concentrate on developing newly recruited investigators while promoting initiatives to enhance its research capacity and direction. This year (FY06) the Center received 25 funding requests, and will expend approximately $515,000 to fund 20 projects in the College of Veterinary Medicine and the College of Agricultural Sciences and Natural Resources. In addition, $50,000 has been committed for purchasing essential research equipment.

The Center will continue to pursue collaborative projects with other units to enhance research that supports its objectives and to contribute significantly to the research enterprise of the College of Veterinary Medicine, the Institute of Agriculture, and the University. Collaborative projects will include the Tennessee Agriculture Experiment Station, the Food Safety Center of Excellence, the Center for Environmental Biotechnology, and the Departments of Microbiology, Nutrition, and Mechanical, Aerospace and Biomedical Engineering.

Bio- and agroterrorism continue as issues of national concern. The Center will continue to support public health oriented projects designed to support surveillance,

intervention, and resolution of potential attacks directed against humans and food animals. The Center will continue to foster interaction among faculty and state, local, and federal programs and personnel through continued co-sponsorship of conferences that address critical issues. The Center will continue to co-sponsor workshops designed to train and certify key personnel likely to respond to an agricultural incident.

The Center will continue to increase its involvement in research training of veterinary students and graduate students by providing increased opportunities for summer internships, matching travel grants, and stipend upgrades to help recruit and retain top quality graduate students. The Center will continue to offer "invited speaker" courses in Microbial Pathogenesis and Mechanisms of Disease, a program which has increased national and international exposure of the Center's faculty, students, and programs; and, at the same time, enhanced the potential for developing external collaborations for our faculty and postdoctoral opportunities for our students.

The Center will continue to participate conceptually and materially in strategic planning to develop areas of investigative strength in the College of Veterinary Medicine and the Institute of Agriculture.

► Identify and pursue internal and external strategic collaborations to enhance research capacity

► Support projects designed for surveillance, prevention, and resolution of acts of bio-and agroterrorism

► Enhance research training of veterinary students and graduates students

► Increase national and international exposure of faculty, students, and programs

Faculty Reports

The following reports provide highlights of 2005 faculty research results.

Animal Models and Comparative Medicine

Dr. Hildegard Schuller 14

Dr. Hwa-Chain Wang 15

Dr. Howard Plummer, III 16

Dr. Patricia Tithof 17

Dr. Seung Joon Baek 18

Dr. Mei-Zhen Cui 19

Dr. Xuemin Xu 20

Dr. Steve Kania 21

Dr. Michael Fry 22

Dr. Michael McEntee 23

Mechanisms of Disease, Pathogenesis, and Immunity

Dr. Barry Rouse 24

Dr. Pamela Small 25

Dr. David Brian 26

Dr. Stephen Oliver 27

Dr. Gina Pighetti 28

Dr. James Godkin 29

Dr. Frank Andrews 30

Dr. Terry Schultz 31


Regulatory Mechanisms in Lung Cancer

East Tennessee has one of the highest lung cancer rates in the United States.

Dr. Schuller's research is focused on specific receptors and pathways that regulate small cell lung carcinoma and pulmonary adenocarcinoma, and how specific toxins in cigarette smoke interact with these pathways.

Pulmonary adenocarcinoma (PAC) is the most common type of non-small cell lung cancer. There are two phenotypically different types of PAC: PAC with features of bronchiolar Clara cells (PACC) and PAC with features of alveolar type II cells (PAC-type II). PACC and PAC-type II are not under the control of the same signaling pathways.

Recent studies in Dr. Schuller's lab indicate that some widely advertised chemopreventive agents, such as green tea and beta carotene, inhibit cell growth in PACC cells, while promoting cell growth in PAC-type II cells.

Smokers with chronic respiratory conditions are at increased risk for lung cancer. Results from Dr. Schuller's studies indicate that certain compounds found in over-the-counter medications may promote cell growth of certain cancer cells, which suggests that some of these medications may be harmful to smokers.

Current studies are ongoing to identify signaling pathways that control the progression of premalignant lesions and initiated cells of different phenotypes to overt cancers of different types.

Hildegard Schuller D.V.M., Justus Liebig University, Giessen, Germany Distinguished Professor, Department of Pathobiology Nine refereed publications in 2005 In addition to Center funds, Dr. Schuller's research is supported by the National Institutes of Health and the Department of Energy


Proapoptotic Role of Ras Oncogene in Anticancer Therapeutics

Mutations in ras proteins are the most common genetic alterations found in human cancers. Ras is a family of proteins that control many important signaling pathways involved in cell growth, differentiation, and apoptosis, or programmed cell death. Researchers are working to develop anticancer drugs that target the ras pathways.

Dr. Wang has found that ras-related pancreatic cancer cells are susceptible to FR901228, an agent currently under study for the treatment of cancer. Dr. Wang is working to determine the molecular mechanisms involved in several apoptotic signaling pathways that are activated by FR901228.

In a recently published study, Dr. Wang identified the roles of three signaling pathways in the FR901228-induced apoptosis of cells undergoing Ras-induced cellular transformation. Two of

the pathways play anti-apoptotic roles and one plays an apoptotic role in transformed cells.

Current studies in Dr. Wang's lab are directed toward elucidating the molecular basis of the cross-talk among several apoptotic signaling pathways that are selectively activated by FR901228.

Information from these studies could lead to the development of more effective, targeted therapies for the treatment of cancer.

Hwa-Chain Wang B.V.M., National Chung-Hsing University, Taiwan Ph.D., University of Virginia Medical Center Associate Professor, Department of Pathobiology Three refereed publications in 2005 In addition to Center funds, Dr. Wang's research is supported by Philip Morris and the National Science Foundation


The Role of GIRK in Breast Cancer and its Functional Association with Beta-Adrenergic Mediated Signal Transduction

Breast cancer is the leading cancer in women, with approximately 200,000 women diagnosed with this disease each year.

Fortunately, breast cancer is one of the most treatable of all human malignancies if detected early.

Studies have shown that the growth of adenocarcinomas in the lungs, pancreas, and colon are controlled by a receptor in the beta-adrenergic system, which is part of the sympathetic nervous system. Data from Dr. Plummer's laboratory indicate that a subset of breast cancer is also controlled by beta-adrenergic receptors.

Dr. Plummer's group recently found a functional link between the beta-adrenergic receptor pathway and the G-protein inwardly rectifying potassium channel (GIRK1) in breast cancer cell lines, and the two pathways are involved in regulating the growth of these cancer cells. Dr. Plummer is currently working to determine the growth regulatory mechanisms stimulated by these pathways. Modulation of GIRK channels may be an important tool in diagnosis or treatment of breast cancers.

Ultimately, results from Dr. Plummer's studies will aid in the development of preventative approaches and treatments of breast cancer.

Howard Plummer, III Ph.D., Bowling Green State University Assistant Professor, Department of Pathobiology Four refereed publications in 2005 In addition to Center funds, Dr. Plummer's research is supported by Philip Morris


Polycyclic Aromatic Hydrocarbons (PAHs), and Atherosclerosis

Atherosclerosis, also known as hardening of the arteries, is the leading cause of heart disease and heart attack.

Atherosclerosis occurs when plaque builds up on arterial walls, which impedes blood flow, depriving vital organs of oxygen-rich blood.

A major risk factor for atherosclerosis is urban pollution. Polycyclic aromatic hydrocarbons (PAHs), a significant component of urban pollution, are formed by the incomplete combustion of fossil fuels or other organic substances.

Atherosclerosis is characterized by endothelial cell apoptosis and vascular wall inflammation. PAHs

activate the phospholipase A2/arachidonic acid cascade, a signaling pathway that plays an important role in endothelial cell apoptosis and inflammation.

Dr. Tithof has recently identified specific PAHs that induce endothelial cell apoptosis, however, the mechanisms by which PAHs may influence the development and progression of atherosclerosis are not yet understood. Dr. Tithof is currently working to determine the role of arachidonic acid in PAH-induced apoptosis of endothelial cells, and to identify the specific phospholipase A2 isoforms and downstream metabolizing enzymes responsible for this effect.

Information from Dr. Tithof's studies can provide insight into how exposure to pollutants accelerates heart disease, the leading cause of death in industrialized countries.

Patricia Tithof D.V.M., Michigan State University Ph.D., Michigan State University Associate Professor, Department of Pathobiology Four refereed publications in 2005


Molecular Carcinogenesis: NSAIDS, Dietary Compounds and Tumorigenesis

Non-steroidal anti-inflammatory drugs (NSAIDS) and various dietary compounds are effective chemopreventive and anti-tumorigenic agents for several cancers, most likely through the induction of apoptosis. But, little is known about the specific mechanisms responsible for these properties.

Dr. Baek's research focus is on identifying the molecular mechanisms behind the cancer preventive properties of NSAIDS and certain phytochemicals, which are natural compounds found in fruits and vegetables.

Catechins, also known as tea flavoniods, are phytochemical compounds found in black tea, green tea, wine, grapes, and chocolate. Green tea, which has the highest concentration of catechins, has been found to suppress the growth of various cancer tumors. In a combined in vitro and in vivo study, Dr. Baek is currently working to determine the exact molecular mechanisms by which green tea affects the development and progression of colon cancer.

In addition, Dr. Baek's group recently identified a novel protein that appears to play a pivotal role in mediating the chemopreventive effects of many anti-cancer compounds, including dietary compounds and NSAIDS. This newly identified protein, nonsteroidal anti-inflammatory activated gene-1 (NAG-1) is induced by NSAIDS, has anti-tumorigenic properties, and stimulates apoptosis in colon cancer cell lines and in other cancer cell lines as well. Dr. Baek's data indicate that the pro-apoptotic activity of NSAIDS may be linked to the expression of NAG-1.

Dr. Baek's studies could lead to the development of new drugs for cancer treatment and to the development of dietary supplements designed to reduce the risk for cancer.

Seung Joon Baek Ph.D., University of Maryland Assistant Professor, Department of Pathobiology Nine refereed publications in 2005 In addition to Center funds, Dr. Baek's research is supported by the National Institutes of Health


Role of Oxidized Lipids and PLA in the Development of Atherosclerosis

Atherosclerosis accounts for 75% of deaths from cardiovascular disease.

The buildup of fatty deposits and other cellular debris, or plaque, on the arterial walls can erode the wall of the artery, reduce elasticity, and impede blood flow.

Plaques that rupture cause the formation of a clot inside a blood vessel (atherothrombosis), which can obstruct blood flow and lead to myocardial infarction, stroke, and sudden death.

Cigarette smoking increases the incidence of cardiovascular diseases such as atherosclerosis and thrombosis. Reports indicate that smoking

accelerates perioxidation of low density lipoproteins (LDL) in plasma and arterial tissues and that elevated levels of oxidized LDL worsen atherosclerotic lesions and promote thrombosis.

Dr. Cui is investigating the roles certain lipids generated by cigarette smoking have in the regulation of tissue factor (TF), an important molecule in the development of atherothrombosis and atherosclerosis. Recently, Dr. Cui found that lysophosphatidic acid (LPA), a component of oxidized LDL, markedly increases tissue factor activity, tissue factor protein, and tissue factor messenger RNA in smooth muscle cells, one of three major resident cell types in atherosclerotic lesions. Dr. Cui is currently investigating the molecular mechanisms by which lipid perioxidation products regulate the expression of tissue factor.

Information from Dr. Cui's research could lead to the identification of novel therapeutic targets for preventing and curing smoking-induced vascular diseases.

Mei-Zhen Cui Ph.D., Tokyo Institute of Technology, Japan Assistant Professor, Department of Pathobiology Two refereed publications in 2005 In addition to Center funds, Dr. Cui's research is supported by the National Institutes of Health, the American Heart Association, Philip Morris, and Pfizer


Pathogenesis of Alzheimer’s Disease

More than 15 million people, worldwide, suffer from Alzheimer’s disease.

Alzheimer's disease is characterized by plaques and tangled bundles of fibers in and around the brain cells. These plaques are made up of beta amyloid, a toxic protein fragment cleaved from a larger protein called amyloid precursor protein, or APP. Cleavage of APP, which is crucial in the pathogenesis of Alzheimer’s disease, occurs in a series of sequential steps.

Because the formation of beta amyloid peptides is believed to be a contributing event in the development of Alzheimer's disease, the molecular mechanisms underlying the formation of these peptides are of considerable interest to researchers. Dr. Xu's research is focused on identifying these mechanisms.

Dr. Xu and his group recently discovered a new, longer species of beta amyloid peptide. This significant discovery provides important insight into the mechanism by which beta amyloid is produced during the gamma-secretase-mediated processing of APP. Given that the longer beta amyloid peptides are more pathogenic than the shorter ones, Dr. Xu's discovery could lead to new targets for the development of methods of preventing and treating Alzheimer's disease, especially those aimed at the design of gamma-secretase inhibitors.

Dr. Xu's paper detailing this study appeared in the December issue of the Journal of Biological Chemistry and was selected as "Paper of the Week" because of the significance of the results reported. Papers that rank in the top 1% of the 6,600 papers published by the journal each year are selected as "Paper of the Week."

Xuemin Xu Ph.D., Institute of Technology, Japan Associate Professor, Department of Pathobiology Three refereed publications in 2005 In addition to Center funds, Dr. Xu's research is supported by the National Institutes of Health


Horizontal Transfer of Methicillin Resistance between Pathogenic Staphylococci

Staphylococci can cause a wide variety of diseases. Some species of staphylococci infect humans while others infect animals.

Staphylococci are found primarily on the skin and

mucous membranes of humans and animals. Approximately ninety percent of staphylococci are resistant to penicillin and penicillin-derived antibiotics, which makes it difficult to treat staphylococci-related infections.

Methicillin is an antibiotic used to treat infections caused by bacteria, like staphylococci, that carry a resistance to antibiotics. However, methicillin is becoming increasingly less effective because several species of staphylococci, previously susceptible to methicillin, have now acquired resistance to this antibiotic.

The spread of methicillin resistance in staphylococci has become a serious public health concern. It is unknown to what extent staphylococci infecting humans and animals exchange methicillin resistance genes and how these resistance genes are transferred.

Dr. Kania is investigating the mechanism of horizontal transfer of methicillin resistance genes among species of staphylococci. Currently, Dr. Kania is working to determine the genetic profiles of canine isolates of staphylococcus in order to track gene transmission.

Information from Dr. Kania's studies is important for determining the risk of transfer of antibiotic resistance between staphylococci that infect different species, and for developing strategies to control the spread of antibiotic resistance.

Steve Kania Ph.D., University of Florida Associate Professor, Department of Comparative Medicine One refereed publication in 2005 In addition to COE funds, Dr. Kania's research is supported by Mont-Vue Farms


Canine Model of Iron Deficiency

Iron deficiency is prevalent across the globe.

In the United States, iron deficiency affects 700,000 children aged one to two years and 7.8 million teenage girls and women of childbearing age.

Too little iron can interfere with several vital functions, such as oxygen flow from the lungs to tissues, transport of electrons within cells, and enzyme reactions in tissues.

The effects of iron deficiency range from anemia to impaired cognitive development. Severe iron deficiency can result in death. A panel of biochemical tests is used to diagnose iron deficiency, but there is no 'gold standard' assay.

Retrospective studies show that novel indices better predict iron deficiency in humans. Ethics prohibit inducing iron deficiency in humans and there has been little investigation, using animal models, as to how new hematological indices change as iron status changes. As a result, researchers have limited understanding of how these new indices might be used to detect iron deficiency at the earliest stage or as it resolves.

Dr. Fry is using a canine model of iron deficiency to study changes in certain novel indices over time, as iron deficiency develops and resolves. Results from Dr. Fry's studies could lead to the ability to detect iron deficiency earlier than currently is possible with conventional methods. Iron deficiency is sometimes an indication of an underlying, undiagnosed health problem. Earlier detection of iron deficiency could lead to earlier diagnosis of serious illnesses and diseases, many of which are treatable if caught near the onset.

Dr. Fry's studies could also establish the necessary foundation for further experimental investigation in animal models and clinical investigation in humans.

Michael Fry Ph.D., University of Wisconsin-Madison Assistant Professor, Department of Pathobiology Two refereed publications in 2005


Intestinal Parasitism and Protective Response

Intestinal nematode parasitism is a common cause of illness and death in people and animals worldwide. Nematodes (round, unsegmented worms), are ubiquitous in aquatic and terrestrial environments. This microscopic parasite can enter the host's body through an unprotected cut or via an insect bite. The host could also acquire the parasite by ingesting contaminated food or water. Whether or not the host rejects the parasite depends on the complex interaction between the nematode and the host's innate and acquired immune system.

Mucosal surfaces, such as the gut, possess a unique immune system in which Th2 – a helper T-cell – plays a key role in orchestrating an integrated defense against infection. The arachidonic acid (AA) cascade is an important signaling pathway that produces more than 100 bioactive lipid mediators that play important roles in a number of Th2-mediated diseases. However, there is little known about the role of AA in host defense against intestinal parasites.

The protective response of mice to intestinal parasitism has been extensively studied as a model of disease in humans and domestic animals. Using a 'hookworm,' which is a significant parasite in humans and domestic animals, Dr. Fry is investigating whether and how the protective response activates AA in a mouse model.

Identifying the specific molecular mechanisms involved in the protective response to intestinal parasitism could lead to the development of dietary or pharmacological strategies to clear the infection.

Michael McEntee D.V.M., Cornell University Professor, Department of Pathobiology Two refereed publications in 2005 In addition to Center funds, Dr. McEntee's research is supported by the National Institutes of Health


Herpes Simplex Immunity

Herpes simplex virus (HSV) infects up to 80% of the human population. HSV persists indefinitely in infected individuals, with some suffering painful periodic lesions.

Dr. Rouse's group is currently working to understand how HSV interacts with the immune system. Their aim is to understand how cells and molecular events set into play by HSV lead to chronic inflammatory lesions or resolution of the disease.

Recently, the discovery of heat shock proteins (hsp) as an adjuvant and a delivery agent has renewed interest in peptide vaccines. Dr. Rouse’s group and other researchers have shown that hsp70 coupled to a peptide acts as a potent immunogen by inducing a protective, peptide specific CD8 response -- CD8 cells are a type of T-cells that look for infected cells, then attack and kill them. However, this protection had poor memory response and lasted only a few days. Memory response is associated with protection against re-infection. Dr. Rouse's group is investigating the factors that contribute to poor memory CD8 response.

Recently, Dr. Rouse's group showed, for the first time, that the hsp70-peptide system can be used to induce helper T-cell and antibody responses. More importantly, the co-administration of hsp70 linked to a CD8 peptide along with the hsp70 linked to helper peptides resulted in 3-fold improvement in CD8+ T-cell memory. Results from Dr. Rouse's studies could have important implications for development of novel strategies for the prevention of viral diseases in people and animals.

Dr. Rouse's research continues to attract national and international interest and his laboratory is recognized as one of the premier viral immunology programs in the country.

Barry Rouse BVSc., University of Bristol, England Ph.D., University of Guelph DSc., University of Bristol, England Distinguished Professor, Department of Pathobiology Sixteen refereed publications in 2005 In addition to Center funds, Dr. Rouse's research is supported by the National Institutes of Health


Pathogenesis of Mycobacterium ulcerans Infection

Mycobacterium ulcerans is the causative agent of Buruli Ulcer, a persistent, flesh-eating skin disease. Buruli Ulcer is present in several countries, but is a severe emerging infectious disease in West Africa.

Research indicates that humans do not get M. ulcerans from other humans or animals, but directly from the environment, possibly through a break in the skin or an insect bite. The exact mode of transmission is not yet known, but slow-moving or stagnant water appears to be a factor in transmission of the bacterium.

In collaboration with the World Health Organization and Dr. Richard Merritt, at Michigan State University, Dr. Small is conducting studies in Ghana in order to identify the source of M. ulcerans in the environment.

Dr. Small’s group has isolated and characterized a polyketide-

derived macrolide toxin (mycolactone) from M. ulcerans and has shown that this toxin is responsible for the unique pathology of Buruli ulcer.

Currently, Dr. Small is investigating how mycolactone regulates or modifies immune functions in human cells and in animal models.

The goal of Dr. Small's research is to identify the cellular targets of mycolactone in order to understand the underlying mechanism of immunosuppression in Buruli Ulcer patients.

Pamela L.C. Small Ph.D., Stanford University Associate Professor, Department of Pathobiology Five refereed publications in 2005 In addition to Center funds, Dr. Small's research is supported by the National Institutes of Health and the World Health Organization


Molecular Pathogenesis of Coronavirus

Coronavirus infections cause respiratory and gastroenteric diseases in livestock and fowl, and chronic, disabling diseases in humans.

In their efforts to identify methods of controlling coronavirus infections, researchers have been frustrated by an incomplete understanding of how coronaviruses replicate, the ability of coronaviruses to rapidly mutate into new pathogenic variants, and animals' generally weak immune response to coronavirus vaccination.

The primary research focus in Dr. Brian's laboratory concerns the molecular events that occur during coronavirus replication, particularly the cis- and trans-acting factors involved in the regulation of RNA regulation and gene transcription. Understanding the molecular mechanisms that regulate virus replication could lead to the development of strategies designed to interrupt the process, which could lead to a cure of virus infection.

Dr. Brian's group has made significant progress toward understanding how specific genetic elements in the coronavirus function to regulate the production of viral proteins and progeny. Dr. Brian's group has identified three cis-acting replication elements of the bovine coronavirus; they are currently working to identify the specific proteins that interact with these elements, and to characterize the interactions.

Results from Dr. Brian's ongoing studies could significantly impact the design of new therapeutic drugs.

David Brian D.V.M., Michigan State University Ph.D., Michigan State University Professor, Department of Pathobiology Three refereed publications in 2005 In addition to Center funds, Dr. Brian's research is supported by the National Institutes of Health


Prevalence, Distribution and Antimicrobial Resistance Patterns of Pathogens on Dairy Farms

Antimicrobials are used extensively in food-producing animals to treat and prevent disease, and to promote growth. There is growing scientific interest regarding the use of antimicrobials in food-producing animals because of the potential for emergence and dissemination of multiple-drug-resistant zoonotic bacterial pathogens.

Antimicrobial drug-resistant bacterial pathogens pose a risk not only to animal health, but also to humans via transmission of foodborne pathogens.

Dairy farms are a major source of foodborne pathogens that could be transmitted to humans. During extensive, on-going farm-based studies, Dr. Oliver’s group established the prevalence of foodborne pathogens in bulk tank milk (BTM) and feces from cull dairy cows, and confirmed that these were potential sources of E. coli O157H7 and Salmonella spp. Dr. Oliver's group is also conducting molecular and antibiotic resistance characterization of L. monocytogenes and C. jejuni isolated from farms in the study.

The data from these studies will be used to define pathogen distribution within and among production areas, and to identify the environmental sources of specific pathogen subtypes in different production areas.

This information is important for developing practices to control the growth of the pathogens in livestock. Antibiotic susceptibility profiles and prevalence of

antimicrobial resistance genes from isolates will provide information on the emergence, persistence, and dissemination of antibiotic resistance.

Stephen Oliver Ph.D., The Ohio State University Professor, Department of Animal Science Eight refereed publications in 2005 In addition to Center funds, Dr. Oliver's research is supported by the USDA, the East Tennessee Clinical Research Initiative, and Pfizer


Host Mechanisms that Contribute to Pathogenesis

Bovine mastitis costs dairy producers in the United States over $15 billion annually. Mastitis is an inflammatory reaction of the mammary gland, usually caused by infection.

The susceptibility of animals to certain diseases, such as mastitis, varies widely across and within species. The goal of Dr. Pighetti's research is to better understand why certain animals become sicker than other animals, so that more effective preventive and therapeutic strategies can be used in the future to combat disease.

Dr. Pighetti's laboratory has recently discovered a marker within a gene that identifies cattle more susceptible to mastitis. This particular gene encodes a receptor for interluekin-8, which is a key regulator of innate immune responses. Dr. Pighetti's work has demonstrated that neutrophils, a type of immune cell that fights off infections, have an impaired ability to migrate, and as such, may have difficulty getting to the site of infection. In cows more susceptible to infection, neutrophils also have a tendency to produce fewer reactive oxygen species, which could also contribute to the increase in infections.

Dr. Pighetti is working to identify why these changes in neutrophils occur at a cellular and molecular level, which could lead to a means of therapeutically boosting the immune response. Not only could such studies offer clues in how to boost the immune response, they may also provide novel strategies for 'switching off' the inflammatory response in cases where extensive inflammatory tissue damage can occur, such as in pneumonia.

Gina Pighetti Ph.D., Pennsylvania State University Assistant Professor, Department of Animal Science One refereed publication in 2005 In addition to Center funds, Dr. Pighetti's research is supported by the U.S. Army and Merial


Reproductive Biology

Overpopulation is one of the most pressing concerns of the 21st century. Overpopulation refers to the ratio of people to available resources necessary for survival, such as food and water.

Scientists are conducting research in reproduction in an effort to help maintain an adequate balance between people and resources. Such research could lead to novel, safe and effective methods of contraception and increase the supply of food animals through improved reproductive efficiency of livestock.

A major focus in Dr. Godkin's laboratory is on those factors that control the development of the early embryo of domestic livestock.

Dr. Godkin's laboratory recently discovered that viability of embryos was improved in animals treated with retinoids just prior to ovulation. They also found that embryonic development was

improved in embryos treated with retinoids. Retinoids are vitamin A-like compounds that are important regulators of vertebrate development, cell differentiation, and tissue function.

Dr. Godkin is working to determine the mechanisms by which retinoids affect egg maturation, embryonic development and embryonic survival. Long term goals of this research are to improve reproductive efficiency in livestock and to develop more efficient assisted reproductive procedures.

Information from these laboratory studies could lead to improvements in assisted reproductive procedures in humans.

James Godkin Ph.D., University of Massachusetts Professor, Department of Animal Science Two refereed publications in 2005


Pathogenesis of Equine Gastric Ulcers

In the United States, owners spend $15 billion annually to maintain over 5.2 million horses. The horse industry contributes $25.3 billion to the gross domestic product.

Equine Gastric Ulcer Syndrome (EGUS) is common in almost all horses, but especially in race and performance horses. EGUS can be treated with a variety of drugs that are expensive and must be administered over a period of several weeks. The economic impact of EGUS is unknown, but, researchers estimate prevalence to be from 25 to 93 percent.

Racehorses fed high concentrate (grain) diets may be more likely to develop gastric ulcers due to byproducts and volatile fatty acids (VFAs) that are produced when these diets are fermented by resident bacteria. Because the concentration of stomach acid is high, these VFAs may cause injury and gastric ulcer when absorbed through the stomach wall.

Dr. Andrews' research suggests that low pH stomach acidity and VFAs in contact with the stomach lining leads to cell damage. Damaged cells lose their ability to transport sodium, which leads to cellular swelling that eventually can lead to cell death and gastric ulceration. Dr. Andrews' results indicate that diets low in fermentable carbohydrates and high in protein and calcium, such as in alfalfa hay, may be helpful in reducing stomach acid and VFAs, which could aid the prevention of equine gastric ulcer disease.

Dr. Andrews is investigating the specific roles of VFAs, calcium, and pH to clarify the cause of EGUS and determine why some horses are resistant to treatment. Results from these studies could lead to the development of antiulcerogenic diets or feed additives that could prevent gastric ulcer in horses that are at high risk.

Frank Andrews D.V.M., Washington State University Professor, Department of Large Animal Clinical Sciences Five refereed publications in 2005


Biosurveillance, Agricultural, and Environmental Security

Exposed to stress, chemicals or toxins, cells respond by altering the pattern of gene expression within their chromosomes. Genes are transcribed into messenger RNA, which acts as the blueprint for making specific proteins, which in turn serve various cellular functions in response to the exposure.

By examining the effects of model compounds on cells associated with the immune system, Dr. Schultz is developing a database of gene expression profiles, or 'fingerprints,' that could be used to predict the hazard of other chemicals.

Information from these model studies will then be used to genetically engineer biosensors, which could be released and monitored remotely to identify chemical and biological agents present in the environment.

Dr. Schultz's current effort is part of a collaborative project funded by the Department of Defense and directed toward developing a biosurveillance web of microbial and plant sensors engineered to detect explosives, chemicals, or biological agents in areas of troop deployment.

The technologies resulting from this project could have direct applicability to agriculture and homeland security as these bio-based sensors could be used to detect bacterial pathogens in food and to identify toxins and their effects on people or crops.

Terry Schultz Ph.D., The University of Tennessee Professor, Department of Comparative Medicine Ten refereed publications in 2005 In addition to Center funds, Dr. Schultz’ research is supported by the Department of Defense and the Environmental Protection Agency

Publications and Presentations

Frank Andrews Frank N, Andrews FM, Elliott S, et al. 2005. The effect of dietary oils on development of gastric ulcers in horses. American Journal of Veterinary Research 66:2006-2011. Frank N, Andrews FM, Elliott S, et al. 2005. Effects of rice bran oil on plasma lipid concentrations, lipoprotein composition, and glucose dynamics in mares. Journal of Animal Science 83:2509-2518, 2005. Andrews FM, Buchanan BR, Elliott SB, et al. 2005. Gastric ulcers in horses. Journal of Animal Science 83(E. suppl):E18-E21. Eiler H, Frank N, Andrews FM, et al. 2005. Physiologic assessment of blood glucose homeostasis via combined intravenous glucose and insulin testing in horses. American Journal of Veterinary Research 66:1598-1604. Buchanan BR, Sommardahl CS, Rohrbach BW, Andrews FM. 2005. Effect of a 24-hour infusion of an isotonic electrolyte replacement fluid on the renal clearance of electrolytes in healthy neonatal foals. Journal of the American Veterinary Medical Association 227:1123-1129. Andrews FM. Cerebrospinal fluid evaluation. In Equine Internal Medicine. Reed SM, Bayly WM, Sellon DC, (eds) 2nd Edition. Saunders Co., St. Louis, MO. 542-546. Andrews FM. Electrodiagnostic aids and selected neurologic diseases. In Equine Internal Medicine. Reed SM, Bayly WM, Sellon DC, (eds) 2nd Edition. Saunders Co., St. Louis, MO. 546-560. Andrews FM. Seizures, narcolepsy, and cataplexy. In Equine Internal Medicine Reed SM, Bayly WM, Sellon DC, (eds) 2nd Edition. Saunders Co., St. Louis, MO. 560-566. Andrews FM. Ulcers in the stomach and colon. In Proceedings American Association of Equine Practitioners Focus Meeting on Equine colic. Quebec City, Quebec, Canada. July 31-August 2, 2005:70-76. Andrews FM, Buchanan BR, Smith S, et al. Pathogenesis of acid injury in the nonglandular equine stomach: The concentration effect of volatile fatty acids. In Proceedings 8th International Equine Colic Research Symposium, Quebec City, Quebec, CA., August 3-5, 2005:61-62. Witonsky S, Gogal R, Yang, Norton H, Ward D, Duncan R, Lindsay D, Ellison S, Andrews F, et al. Focus on infectious diseases: EPM and Brucella spp. VMRCVM Research Symposium. Blacksburg, VA.


Witonsky S, Ellison S, Yang J, Gogal R, Norton H, Andrews F, et al. In vitro alterations in immune function associated with experimental infectino of horses with Sarcocystis neurona. ACVIM Forum SIG, Baltimore, MD. 2005. Ellison S, Witonsky S, Yang J, Gogal R, Norton H, Andrews F, et al. Parasitemia to paresis: A model for S. neurona Equine Protozoal Myeloencephalitis (EPM). ACVIM Forum SIG. Baltimore, MD. 2005. American Association of Equine Practitioners Focus on Equine Colic Meeting, Quebec City, Quebec, Canada, July 31-August 2, 2005. Ulcers in the Stomach and Colon of Horses: Diagnosis and Treatment: A Pain in the Gut. Seung Joon Baek Baek SJ, Kim JS, Moore SM, Lee SH, Martinez J, and Eling TE. 2005. Cyclooxygenase inhibitors induce the expression of the tumor suppressor gene EGR-1, which results in the up-regulation of NAG-1, an anti-tumorigenic protein. Mol Pharmacol. Feb. 67(2): 356-364. Cho KN, Choi JY, Kim CH, Baek SJ, Chung KC, Moon UY, Kim KS, Lee WJ, Koo JS, and Yoon JH. 2005. Prostaglandin E2 Induces MUC8 Gene Expression via a Mechanism Involving ERK MAPK/RSK1/CREB Activation in Human Airway Epithelial Cells. J Biol Chem. Feb 280(8): 6676-6681. Lee SH, Kim JS, Yamaguchi K, Eling TE, and Baek SJ. 2005. Indole-3-carbinol and 3,3'-diindolylmethane induce expression of NAG-1 in a p53-independnet manner. Biochem Biophys Res Commun. Mar. 328(1):63-69. Kim JS, Baek SJ, Sali T, and Eling TE. 2005. The conventional nonsteroidal anti-inflammatory drug sulindac sulfide arrests ovarian cancer cell growth via the expression of NAG-1/MIC-1/GDF-15 Mol Cancer Ther. Mar. 4(3):487-493. Kim JH, Yamaguchi K, Lee SH, Tithof PK, Sayler GS, Yoon JH, and Baek SJ. 2005. Evaluation of polycyclic aromatic hydrocarbons in the activation of early growth response-1 and peroxisome proliferator activated receptors. Toxicol Sci. May 85(1):585-593. Kim JS, Baek SJ, Bottone FG, Sali T and Eling TE. 2005. Over-expression of 15-lipoxygenase-1 induces growth arrest via phosphorylation of p53 in human colorectal cancer cells .Mol Cancer Res. Sep 3(9):511-7. Yoon JH, and Baek SJ. 2005. Molecular Targets of Dietary Polyphenols with anti-inflammatory Properties. Yonsei Med J. Oct. 46(5):585-596.


Chintharlapalli S, Papineni S, Baek SJ, Liu S, and Safe S. 2005. 1,1-Bis(3’-indolyl)-1-(p-substitutedphenyl)methanes Activate peroxisome proliferators-activated receptor g in HCT-116 colon cancer cells but decreased cell survival through receptor-independent activation of NAG-1. Mol Pharmacol. In Press. Yamaguchi K, Liggett J, Kim NC, and Baek SJ. 2005. Anti-proliferative effect of horehound leaf and wild cherry bark extracts on human colorectal cancer cells. Oncol Rep. In Press. Whealan J, McEntee MM, and Baek SJ. 2005. Dietary polyunsaturated fatty acids, eicosanoids, and intestinal tumorigenesis. Carcinogenic & Anticarcinogenic Food Components. CRC Press. pp 157-176. Nam-Cheol Kim, Kiyoshi Yamaguchi , Jason L Liggett, Baek SJ. Activity of four New Mexican medicinal plants on NAG-1 and cyclin D1 in human colorectal cancer cells. 46th Annual Meeting of the American Society of Pharmacognosy, July 2005 Corvallis OR. Kiyoshi Yamaguchi , Seong-Ho Lee, Thomas E. Eling, Baek SJ. Phosphatidylinositol 3-kinase/AKT/glycogen synthase kinase-3β pathway down-regulates ant i-tumorigenic protein NAG-1 in human colorectal cancer cells. Seong-Ho Lee, Kiyoshi Yamaguchi, Thomas E. Eling, Baek SJ. CLA induces apoptosis in human colorectal cancer cells. American Association for Cancer Research 96th Annual Meeting, April 2005 Anaheim CA. Anti-inflammatory property of Dietary polyphenols. The 1st symposium on biomolecule secretion. Yonsei medical University, Seoul, Korea, Oct 16, 2005. David Brian Brian, David A. and Ralph Baric. 2005. Coronavirus genome structure and replication. Current Topics in Microbiology and Immunology. 287:1-30. Raman, Sharmila, and David A. Brian. 2005. Stem-loop IV in the 5’ UTR is a cis-acting element in bovine coronavirus DI RNA replication. J. Virol. 79:12434-46. Wu, Hung-Yi, Aykut Ozdarendeli, and David A. Brian. 2005. The bovine coronavirus 5’-proximal genomic acceptor hotspot for discontinuous transcription is 65-nt wide. J. Virol. 80:2183-93. Mei-Zhen Cui Zhao, G., Cui M.-Z., Mao, G., Tan, J,, Dong Y, Sun, L. and Xu, X. 2005. g-cleavage is dependent on z-cleavage during the proteolytic processing of amyloid precursor protein within its transmembrane domain. J. Biol. Chem. 280(45): 37689-37697.


Dong, Y., Tan, J. Cui, M. Z., Zhao, G., Mao, G. Singh, N. and Xu, X. 2005. Calpain inhibitor MDL28170 modulates Ab formation by inhibiting the formation of intermediate Ab 46 and protecting Ab from degradation. FASEB Journal, 2006 Feb;20(2):331-3. Epub 2005 Dec 14. Cui, M.-Z. Laag, E., Sun, L., Xu, X. Atorvastatin Research Award Summit meeting (Key Biscayne, Florida). Abstract: Serum response factor and CREB are responsible for lysophosphatidic acid-induced Egr-1 expression. Feb. 5, 2005. Cui, M.-Z. Laag, E., Zhao, G. Sun, L., Tan, M. and Xu, X. Lysophosphatidic Acid Induction of Early Growth Response Gene Egr-1 Expression in Vascular Smooth Muscle cells. 6th

Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology, April 28-30, 2005, Washington DC. Cui, M.-Z. Feb. 5, 2005, at Atorvastatin Research Award Summit meeting (Key Biscayne, Florida). " Serum response factor and CREB are responsible for lysophosphatidic acid-induced Egr-1 expression". Mike Fry Fry MM, Walker NJ, Blevins GM, Magdesian KG, Tablin F. 2005. Platelet function defect in a thoroughbred filly. J Vet Intern Med 2005;19(3):359-362. Sykes JE, Ball LM, Bailiff NL, Fry MM. 2005. 'Candidatus Mycoplasma haematoparvum' sp. Nov., a novel small haemotropic mycoplasma from a dog. Int J Syst Evol Microbiol 55(Pt 1):27-30. Fry MM. Diagnostic Cytology of Lymph Nodes and Hematopoietic Neoplasia. University of Tennessee College of Veterinary Medicine Continuing Education Series, Knoxville TN, 12/8/05. Fry MM, Irizarry AR, Craig LE, Allender M, Johnson A, Jones M. Cytoplasmic inclusions in leukocytes from an Eastern box turtle (Terrapene carolina carolina). ASVCP Case Review Session, American Society for Veterinary Clinical Pathology 40th Annual Meeting, Boston MA, 12/6/05. Fry MM, Kirk CA. Reticulocyte indices in a canine model of nutritional iron deficiency. University of Tennessee Graduate School of Medicine Research Seminar Series, Knoxville TN, 11/15/05. Fry MM, Kirk CA. Reticulocyte indices in a canine model of nutritional iron deficiency. Bayer Advia 120/2120 User Meeting, Memphis TN, 9/13/05. Fry MM. Cytology basics for veterinary practitioners. Tennessee Veterinary Medical Association Music City Veterinary Conference, Nashville TN, 2/19/05.


Fry MM. Emerging diagnostic techniques in veterinary medicine. Tennessee Veterinary Medical Association Music City Veterinary Conference, Nashville TN, 2/19/05. Fry MM. Emerging diagnostic techniques in veterinary medicine. University of Tennessee College of Veterinary Medicine Alumni Weekend Breakfast with the Professor, 2/5/05. James Godkin Livingston, T.E., Eberhardt, D.M., Edwards, J.L., Godkin, J.D. 2004. Metabolism of sheep oocytes during in vitro maturation JAVA 3: 174-181. Livingston, T.E., Eberhardt, D.M., Godkin, J.D. 2005. Retinol improves bovine embryonic development in vitro. Biol Reprod Endocrinol 2: 83-89. Steve Kania Kania, S.A. and C.R. Reinemeyer. 2005. Anoplocephala perfoliata coproantigen detection: a preliminary study. Vet. Parasitology 127:115-119. Pickens, K.A., Cheng, (Max) Z., Kania, S.A., Effects of Colchicine and Oryzalin on Callus and Adventitious Shoot Formation of Euphorbia pulcherrima ‘Winter Rose’™ American Society for Horticultural Science Annual Conference, Las Vegas, Nevada, July 20, 2005. Kania, S.A., L. Johnson, E. Ofori, R. Jones, D.A. Bemis. Coagulase gene variability in Staphylococcus aureus isolated from animals. Conference of Research Workers in Animal Disease. St. Louis, MO November 2005. Mike McEntee Whelan J, McEntee MF, Baek SJ. 2005. Dietary polyunsaturated fatty acids, eicosanoids and intestinal tumorigenesis. Carcinogenic and Anticarcinogenic Food Components; Editors: Baer-Dubowska W, Bartoszek A, Malejka-Giganti D. CRC Press, Boca Raton, Florida. Moon Y, Bottone FG, McEntee MF, Eling TE. 2005. Suppression of tumor cell invasion by cyclooxygenase inhibitors is mediated by thrombospondin-1via the early growth response gene, Egr-1. Molecular Cancer Therapeutics 4:1551-1558. Peinovich M, McEntee M, Le S, Lester T, Passage M, Kakkis E. Immune tolerant mucopolysaccharidosis I-affected dogs have improved glycosaminoglycan storage reduction with enzyme replacement therapy. Society for Inherited Metabolic Disorders Annual Meeting, Pacific Grove, California, March, 2005. Dickson P, McEntee M, Le S, Guerra C, Hanson S, Peinovich M, Passage M, Kakkis E. Quarterly intrathecal enzyme replacement therapy for canine MPS I. Society for Inherited Metabolic Disorders Annual Meeting, Pacific Grove, California, March, 2005.


Ding S, McEntee MF, Whelan J, Zemel MB. Interaction of Dietary Calcium and Fat Stores in Modulating Intestinal Tumorigenesis. Annual Experimental Biology Meeting (FASEB), San Diego, California, April, 2005. Whelan J, Lee JS, Ding S, McEntee MF, Zemel MB. Diet and Calcium on Intestinal Tumorigenesis. International Research Conference on Food, Nutrition, and Cancer, Washington, DC, July, 2005. Le S , Dickson PI, Vogler C, Levy B, McEntee M, Guerra C, Peinovich MC, Jagabat C, Manuel H, Passage MB, Kakkis, ED. Monthly, quarterly, and low-dose intrathecal iduronidase for canine MPS I. American Society of Human Genetics Annual Meeting, Salt Lake City, Utah, October 2005. McEntee M, Zeigler C, Ray M, Tomer K, Whelan J. Modification of prostate cancer progression by dietary polyunsaturated fatty acids. 9th International Conference: Eicosanoids & Other Bioactive Lipids in Cancer, Inflammation and Related Diseases. San Francisco, California, September 2005. Published in Prostaglandins and Other Lipid Mediators. Steve Oliver Nam, H. M., V. Srinivasan, B. E. Gillespie, S. E. Murinda, and S. P. Oliver. 2005. Application of SYBR green real-time PCR assay for specific detection of Salmonella spp. in dairy farm environmental samples. Int. J. Food Microbiol. 102:161-171. Hockett, M. E., R. A. Almeida, N. R. Rohrbach, S. P. Oliver, H. H. Dowlen, and F. N. Schrick. 2005. Effects of induced clinical mastitis during preovulation on endocrine and follicular function. J. Dairy Sci. 88:2422-2431. Oliver, S. P., B. M. Jayarao, and R. A. Almeida. 2005. Foodborne pathogens in milk and the dairy farm environment: food safety and public health implications. Foodborne Pathogens and Disease 2 (2):115-129. Nam, H. M., V. Srinivasan, S. E. Murinda and S. P. Oliver. 2005. Detection of Campylobacter jejuni in dairy farm environmental samples using SYBR Green real-time polymerase chain reaction. Foodborne Pathogens & Disease 2 (2): 160–168. Oliver, S. P., B. E. Gillespie, S. J. Headrick, M. J. Lewis, and H. H. Dowlen. 2005. Prevalence, risk factors and strategies for controlling mastitis in heifers during the periparturient period. Intl. J. Appl. Res. Vet. Med. 3:150-162. Srinivasan, V., H. M. Nam, L. T. Nguyen, B. Tamilselvam, S. E. Murinda, and S. P. Oliver. 2005. Prevalence of antimicrobial resistance genes in Listeria monocytogenes isolated from dairy farms. Foodborne Pathogens & Disease 2 (3): 201-211.


Gillespie, B. E., and S. P. Oliver. 2005. Simultaneous detection of Staphylococcus aureus, Streptococcus agalactiae and Streptococcus uberis in milk by multiplex real-time polymerase chain reaction. J. Dairy Sci. 88:3510-3518. Murinda, S. E., P. D. Ebner, L. T. Nguyen, A. G. Mathew, and S. P. Oliver. 2005. Antimicrobial resistance and class 1 integrons in pathogenic Escherichia coli. Foodborne Pathogens & Disease 2 (4):348-352. Oliver, S. P., B. M. Jayarao, and R. A. Almeida. 2005. Foodborne pathogens, mastitis, milk quality, and dairy food safety. In: Proc. Natl. Mastitis Counc. pp. 3-27. Oliver, S. P., B. E. Gillespie, H. Moorehead, H. H. Dowlen, D. L. Johnson, K. C. Lamar, M. J. Lewis, S. J. Headrick, S. T. Chester, and W. M. Moseley. 2005. Intramammary ceftiofur therapy for treatment of subclinical and clinical mastitis in lactating dairy cows. In: Proc. Natl. Mastitis Counc. pp. 271-272. Almeida, R. A., D. A. Luther, J. B. Dale, and S. P. Oliver. 2005. M-like proteins of Streptococcus uberis. In: Proc. Natl. Mastitis Counc. pp. 209-210. Oliver, S. P., B. E. Gillespie, S. J. Headrick, M. J. Lewis, and H. H. Dowlen. 2005. Heifer mastitis: Prevalence, risk factors and control strategies. In: Proc. Natural Resource, Agriculture, and Engineering Service Conference on Dairy Calves and Heifers: Integrating Biology and Management, pp. 283-305. Almeida, R. A., B. Tamilselvam, and S. P. Oliver. 2005. Persistence of Streptococcus uberis in bovine mammary epithelial cells. In: Proc. Intl. Dairy Fed. Mastitis Conf. pp. 137-142. Almeida, R. A., and S. P. Oliver. 2005. Binding of host factors influences intracellular trafficking and survival of Streptococcus uberis in bovine mammary epithelial cells. In: Proc. Intl. Dairy Fed. Mastitis Conf. p. 771. Oliver, S. P., D. A. Luther, H. M. Park, and R. A. Almeida. 2005. Identification, isolation, characterization and elucidation of a novel Streptococcus uberis adhesion molecule (SUAM). In: Proc. Intl. Dairy Fed. Mastitis Conf. p. 772. Steinman, K., S. M. Andrew, A. A. Borm, L. K. Fox, K. E. Leslie, J. S. Hogan, S. P. Oliver, Y. H. Schukken, W. E. Owens, and C. Norman. 2005. Prepartum intramammary antibiotic therapy: effect on risk of antibiotic residues in milk from dairy heifers. In: Proc. Intl. Dairy Fed. Mastitis Conf. pp. Gillespie, B. E., and S. P. Oliver. 2005. Simultaneous detection of mastitis pathogens in milk by multiplex real-time polymerase chain reaction. In: Proc. Intl. Dairy Fed. Mastitis Conf. pp. 427-433.


Gillespie, B. E., L. T. Nguyen, H. M. Nam, S. E. Murinda, and S. P. Oliver. 2005. Detection of Escherichia coli O157:H7 and Listeria monocytogenes in beef products by real-time polymerase chain reaction. In: Proc. Intl. Dairy Fed. Mastitis Conf. p. 988. Gillespie, B. E., H. M. Nam, V. Srinivasan, S. E. Murinda, and S. P. Oliver. 2005. Application of SYBR green real-time PCR assays for detection of Salmonella spp. and Campylobacter jejuni in dairy farm environmental samples. In: Proc. Intl. Dairy Fed. Mastitis Conf. p. 989. Srinivasan, V., H. M. Nam, L. T. Nguyen, and S. P. Oliver. 2005. Prevalence of tetracycline and streptomycin resistance genes in Enterobacteriaceae isolated from dairy farm soils. In: Proc. Intl. Dairy Fed. Mastitis Conf. p. 979. Srinivasan, V., L. T. Nguyen, S. E. Murinda, and S. P. Oliver. 2005. Phenotypic and genotypic antimicrobial resistance pattern of Escherichia coli O26 isolated from food and animals. In: Proc. Intl. Dairy Fed. Mastitis Conf. p. 980. Oliver, S. P., B. Tamilselvam, V. Srinivasan, D. A. Luther, B. E. Gillespie, and R. A. Almeida. 2005. Identification of b-defensin genes in bovine mammary epithelial cells. In: Proc. Intl. Dairy Fed. Mastitis Conf. p. 836. Oliver, S. P., S. E. Murinda, L. T. Nguyen, H. M. Nam, R. A. Almeida, and S. J. Headrick. 2005. On-farm sources of foodborne pathogens: isolation from the dairy farm environment. In: Proc. Intl. Dairy Fed. Mastitis Conf. pp. 665-670. Borm, A. A., L. K. Fox, K. E. Leslie, J. S. Hogan, S. M. Andrew, S. P. Oliver, Y. H. Schukken, D. D. Hancock, C. T. Gaskins, W.E. Owens, and C. Norman. 2005. Prepartum intramammary antibiotic therapy: effects on udder health, milk production, and reproductive performance in dairy heifers. In: Proc. Intl. Dairy Fed. Mastitis Conf. pp. 364-369. Dogan, B., S. Klaessig, K. Simpson, S. Oliver, R. Almeida, and Y. Schukken. 2005. Pathogenesis of chronic Escherichia coli intramammary infections. In: Proc. Intl. Dairy Fed. Mastitis Conf. pp. 131-136. Srinivasan, V., B. E. Gillespie, S. Headrick, H. M. Nam, L. T. Nugyen and S. P. Oliver. 2005. Antimicrobial susceptibility patterns of Staphylococcus aureus and Streptococcus spp. isolated from cows with clinical mastitis. In: Proc. Intl. Dairy Fed. Mastitis Conf. p. 981.


Oliver, S. P., B. E. Gillespie, S. J. Headrick, M. J. Lewis, and H. H. Dowlen. 2005. Prevalence and strategies for controlling heifer mastitis during the periparturient period. In: Proc. Boehringer Ingelheim Satellite Symposium on “Targeted Systemic Mastitis Treatment – Key Element in the Control of Subclinical and Heifer Mastitis”, Intl. Dairy Fed. Mastitis Conf. pp. 18-30. Oliver, S. P. 2005. Applications of biotechnology in today’s dairy industry. In: Proc. Am. Assoc. Bovine Practitioners. 38: 99-111. Oliver, S. P. 2005. Impact of mastitis on milk quality and cattle health: proven intervention strategies for cows and heifers. In: Proc. Fort Dodge Dairy Summit at Sundance. pp. 73-92. Oliver, S. P. 2005. Strategies for treating subclinical mastitis in heifers and cows. In: Proc. Pfizer Bovine Practitioner Symposium. Luther, D. A., R. A. Almeida, and S. P. Oliver. 2005. Multiple bioinformatic analyses of Streptococcus uberis adhesion molecule. Abstract in UT-ORNL Bioinformatics Summit. Almeida, R. A., and S. P. Oliver. 2005. Binding of bovine lactoferrin influences intracellular trafficking and survival of Streptococcus uberis. Abstract P9 in Proc. Conference of Research Workers in Animal Diseases. Luther, D. A., R. A. Almeida, and S. P. Oliver. 2005. Detection of Streptococcus uberis adhesin gene in geographically diverse strains of Streptococcus uberis. Abstract P5 in Proc. Conference of Research Workers in Animal Diseases. Luther, D. A., R. A. Almeida,and S. P. Oliver. 2005. Annotation of chromosomal flanking regions of Streptococcus uberis adhesin gene, sua. Abstract P7 in Proc. Conference of Research Workers in Animal Diseases. Luther, D. A., R. A. Almeida, and S. P. Oliver. 2005. Bioinformatic analyses of a Streptococcus uberis Adhesion Molecule (SUAM). Abstract P6 in Proc. Conference of Research Workers in Animal Diseases. Prado, M. E., R. A. Almeida, and S. P. Oliver. 2005. Expression of the recombinant form of a novel surface protein (SUAM) of Streptococcus uberis. Abstract P4 in Proc. Conference of Research Workers in Animal Diseases. Almeida, R. A., D. A. Luther, H. M. Park, M. E. Prado, and S. P. Oliver. 2005. Identification, isolation and characterization of Streptococcus uberis adhesion molecule. USDA/NRI/CSREES Meeting, St. Louis, MO.


Presented an invited seminar entitled "Strategies for treating subclinical mastitis in heifers and cows" at the Pfizer Veterinary Symposium, Bowling Green, KY, December, 2005. Presented an invited seminar entitled "Importance of early intervention for treatment of subclinical mastitis" at the Fort Dodge Animal Health Dairy Summit, Sundance, UT, September, 2005. Presented an invited seminar entitled "Applications of biotechnology in today’s dairy industry" at the American Association of Bovine Practitioners Annual Meeting, Salt Lake City, UT, September, 2005. Presented an invited seminar entitled "Prevalence and strategies for controlling heifer mastitis during the periparturient period" at the Boehringer Ingelheim Satellite Symposium on "Targeted Systemic Mastitis Treatment – Key Element in the Control of Subclinical and Heifer Mastitis", at the 4th International Dairy Federation International Mastitis Conference, Maastrecht, the Netherlands, June, 2005. Presented invited seminars entitled "New and time-tested strategies for the prevention and control of subclinical and clinical mastitis in lactating and nonlactating dairy cows" at the 2005 Dairy Leaders Veterinary Animal Health Symposia held in Sylvester, GA; Pottsboro, TX; Oregon, OH; Wisconsin Dells, WI; Chino, CA; Visalia, CA; Modesto, CA; Clovis, NM; Verona, NY; Phoenix, AZ; and Harrisburg, PA, May/June 2005. Presented an invited seminar entitled "Heifer mastitis: prevalence, risk factors and strategies for control" at the Natural Resource and Engineering Service (an interdisciplinary, issue-oriented program sponsored by cooperative extension of fourteen member land grant universities) Conference, Syracuse, NY, January, 2005. Presented an invited seminar entitled "Foodborne pathogens, mastitis, milk quality, and dairy food safety" at the 44th Annual Meeting of the National Mastitis Council, Orlando, FL, January, 2005. Gina Pighetti Rambeaud, M. and G.M. Pighetti. 2005. Impaired neutrophil migration associated with specific bovine CXCR2 genotypes. Infect Immun. 73:4955-9. Pighetti, G.M. and M. Rambeaud. 2005. “Potential association of polymorphisms in the bovine CXCR2 gene with neutrophil survival and killing ability”. In: Proc. Intl. Dairy Fed Mastitis Conf. pp 185-188. Pighetti, G.M. and M. Rambeaud. 2005. “The ability of neutrophils to migrate is impaired in dairy cows with specific CXCR2 genotypes”, In: Proc. Int. Dairy Fed. Mastitis Conf. pp 770.


Rambeaud, M., A. Pollock, R. Clift and G.M. Pighetti. 2005. Differential intracellular calcium release in neutrophils of cattle with different CXCR2 genotypes upon interleukin-8 activation. In: Proc. Conference Research Workers Animal Diseases P130. Pollock, A., M. Rambeaud, R. Clift and G.M. Pighetti. 2005. Relationship of ligand and dose with neutrophil migration in cows with different CXCR2 genotypes. In: Proc. Conference Research Workers Animal Diseases. P97. Potential association of polymorphisms in the bovine CXCR2 gene with neutrophil survival and killing ability. Intl. Dairy Federation Mastitis Conference. Maastricht, Netherlands. June 2005. CXCR2: A novel marker for immune function and disease susceptibility? Seminar at Department of Pathobiology, College of Veterinary Medicine, University of Guelph. October 7, 2005. Howard Plummer, III Plummer III, H.K., Dhar, M. and Schuller, H.M. 2005. Expression of the α7 nicotinic acetylcholine receptor in human lung cells. Respiratory Research 6: 29. Plummer III, H.K., Dhar, M., Cekanova, M. and Schuller, H.M. 2005. Expression of G-protein inwardly rectifying potassium channels (GIRKs) in lung cancer cell lines. BMC Cancer 5: 104. Dhar, M.S., and Plummer III, H.K. 2005. Protein expression of G-protein inwardly rectifying potassium channels (GIRKs) in breast cancer cell lines. American Society for Cell Biology abstract # 397. Barry Rouse Biswas PS, Banerjee K, Kim B, Rouse, BT, et al. 2005. Role of inflammatory cytokine-induced cycloxygenase 2 in the ocular immunopathologic disease herpetic stromal keratitis. Journal of Virology 79 (24): 15590-15590. Kim B, Kaistha SD, Rouse BT. 2005. Viruses and autoimmunity. Autoimmunity 38 (8): 559-565. Suvas S, Rouse BT. 2005. Regulation of microbial immunity: The suppressor cell renaissance. Viral Immunology 18 (3): 411-418. Kumaraguru U, Banerjee K, Rouse BT. 2005. In vivo rescue of defective memory CD8(+) T cells by cognate helper T cells. Journal of Leukocyte Biology 78 (4): 879-887.


Suvas S, Kim B, Sarangi PP, et al. 2005. In vivo kinetics of GITR and GITR ligand expression and their functional significance in regulating viral immunopathology. Journal of Virology 79 (18): 11935-11942. Biswas PS, Banerjee K, Kim B, et al. 2005. Role of inflammatory cytokine-induced cycloxygenase 2 in the ocular immunopathologic disease herpetic stromal keratitis. Journal of Virology 79 (16): 10589-10600. Azkur AK, Kim B, Suvas S, et al. 2005. Blocking mouse MMP-9 production in tumor cells and mouse cornea by short hairpin (sh) RNA encoding plasmids. Oligonucleotides 15 (2): 72-84. Toka FN, Rouse BT. 2005. Mucosal application of plasmid-encoded IL-15 sustains a highly protective anti-Herpes simplex virus immunity. Journal of Leukocyte Biology 78 (1): 178-186. Kim B, Lee S, Suvas S, et al. 2005. Application of plasmid DNA encoding IL-18 diminishes development of herpetic stromal keratitis by antiangiogenic effects. Journal of Immunology 175 (1): 509-516. Biswas PS, Rouse BT. 2005. Early events in HSV keratitis - setting the stage for a blinding disease. Microbes and Infection 7 (4): 799-810. Pack CD, Kumaraguru U, Suvas S, et al. 2005. Heat-shock protein 70 acts as an effective adjuvant in neonatal mice and confers protection against challenge with Herpes Simplex Virus. Vaccine 23 (27): 3526-3534. Suvas S, Kim B, Waldmann H, et al. 2005. In vivo kinetics of GITR, GITR-L expression and their functional significance in regulating viral immunopathology. FASEB Journal 19 (4): A962-A962 Part 1 Suppl. S. Belkaid Y, Rouse BT. 2005. Natural regulatory T cells in infectious disease. Nature Immunology 6 (4): 353-360. Banerjee K, Biswas PS, Rouse BT. 2005. Elucidating the protective and pathologic T cell species in the virus-induced corneal immunoinflammatory condition herpetic stromal keratitis. Journal of Leukocyte Biology 77 (1): 24-32. Biswas PS, Banerjee K, Kim B, et al. 2005. A novel flow cytometry based assay for quantification of corneal angiogenesis in the mouse model of herpetic stromal keratitis. Experimental Eye Research 80 (1): 73-81.


Toka FN, Gierynska M, Suvas SM, et al. 2005. Rescue of memory CD8(+) T cell reactivity in peptide/TLR9 ligand immunization by codelivery of cytokines or CD40 ligation. Virology 331 (1): 151-158. Banerjee K, Biswas PS, Kumaraguru U, et al. 2005. Protective and pathological roles of virus-specific and bystander CD8(+) T cells in herpetic stromal keratitis. Journal of Immunology 173 (12): 7575-7583. Kim B, Tang QQ, Biswas PS, et al. 2004. Inhibition of ocular angiogenesis by siRNA targeting vascular endothelial growth factor pathway genes - Therapeutic strategy for herpetic stromal keratitis. American Journal of Pathology 165 (6): 2177-2185. Toka FN, Suvas S, Rouse BT. 2004. CD4(+) CD25(+) T cells regulate vaccine-generated primary and memory CD8(+) T-cell responses against herpes simplex virus type 1. Journal of Virology 78 (23): 13082-13089. Rouse, B.T., Pack, C., Kumaraguru, U. 2005. Can we control all viruses with vaccines? South Africa Journal of Science. In press. Rouse, B.T., Lee, S., Zheng, M., and Banerjee, K. 2004. Herpetic Stromal Keratitis - aspects of its pathogenesis. Ed. By M. Zierhut, D. Sullivan, M. Stern. Swets and Zeitlinger Publishers, Sassenheim. The Netherlands. Schmid, D.S., and Rouse, B.T. 2005. Respiratory virus vaccines in Mucosal Immunology, third edition. Ed. By J.R. McGhee and J. Meskecky. Academic Press. NY. In press. Banerjee, K. and Rouse, B.T. 2005. "Immunopathological aspects of HSV infection." In Human Herpesviruses: Biology, Therapy and Immunoprophylaxis. Eds. Arvin, M., Campadelli-Fume, G., Mocarski, E., Roizman, B., Whitley, R., andVamanishi, K. Cambridge University Press, Cambridge, UK. In Press. Pack, C.D., and Rouse, B.T., 2005. Immunity to herpes simples virus: Present but not perfect. Alpha Herpesviruses: Pathogenesis, Molecular Biology and Infection Control. Edited by R.M. Sanri-Golding. The Horizon Press. In press. Polcicova K, Biswas PS, Banerjee K, et al. Herpes keratitis in the absence of anterograde transport of virus from sensory ganglia to the cornea. Proceedings of the National Academy of Sciences of the United States of America 102 (32): 11462-11467 Aug., 9 2005. Policova, K., Biswas, P.S., Banerjee, K., Wisner, T.W., Rouse, B.T., and Johnson, D.C. Herpes Simplex virus persistent in the cornea can cause keratitis. Proceedings of the National Academy of Sciences. In press.


29th International Herpesvirus Workshop. Reno, Nevads, July 25-30, 2004. Chairman of Immunology Section. British Society of Immunology Meeting. Harrogate, England, December 7-11, 2004. ARVA Meeting, May 1-5, 2005. Symposium speaker and chairman of session. 30th International Herpesvirus Workshop. Turku, Finland, july 30 - August 4, 2005. Chairman of Immunology. Hildegard Schuller Plummer III, H. K., Madhu, S. D., Cekanova, M. and Schuller, H. M. 2005. Expression of G-protein inwardly rectifying potassium channels (GIRKs) in lung cancer cell lines. BMC Cancer 5: 104, (open access). Schuller, H.M., Cekanova, M. 2005. NNK-induced hamster lung adenocarcinomas over- express β2-adrenergic and EGFR signaling pathways. Lung Cancer, 49: 35-45. Al-Wadei, H. A. N., Takahashi, T., Schuller, H. M. 2005. Theophylline stimulates cAMP- mediated signaling associated with growth regulation in human cells from pulmonary adenocarcinoma and small airway epithelia. Int J Oncol 27: 155-160. Kabalka, G. W., Mereddy, A. R., Schuller, H. M. 2005. Synthesis of iodine-123 labeled celecoxib analogue: a potential SPECT agent. J Labeled Comp Radiopharm 48: 295-300. Askari, M. D. F., Tsao, M-S., Schuller, H. M. 2005. The tobacco-specific carcinogen, 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone stimulates proliferation of immortalized human pancreatic duct epithelia through β-adrenergic transactivation of the EGF receptor. J Cancer Res Clin Oncol 131: 639-648. Masi, T, Cekanova, M., Walker, K., Majidi, M., Becker, J. M., Schuller, H.M. 2005. Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induced pulmonary adenocarcinomas in Syrian golden hamsters contain beta2-adrenergic receptor single nucleotide polymorphisms (SNPs). GenesChromosomes & Cancer 2005 44: 212-217. Plummer III, H. K., Dhar, M., Schuller, H. M. 2005. Expression of the alpha 7 nicotinic acetylcholine receptor in human lung cells. Respiratory Research 6: 29 (open access). Al-Wadei, H. A. N., Takahashi, T., Schuller, H. M. 2005. Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by β-carotene via activation of cAMP, PKA, CREB and ERK1/2. Int J Cancer 118: 1370-1380.


Al-Wadei, H. A. N., Takahashi, T., Schuller, H. M. 2005. PKA-dependent growth stimulation by dexamethasone of cells derived from human pulmonary adenocarcinoma and small airway epithelium. Eur J Cancer 41: 2745-2733. Al-Wadei, H. A. N., Takahasi, T., Schuller, H. M. 2005. Caffeine stimulates the proliferation of human lung adenocarcinoma cells and small airway epithelial cells via activation of PKA, CREB and ERK1/2. Oncology Reports, 15: 431-535. Terry Schultz Gaglardi, S.R. and Schultz, T.W. 2005. Regression comparisons of aquatic toxicity of benzene derivatives: Tetrahymena pyriformis and Rana japonica. Bulletin of Environmental Contamination and Toxicology 74: 256-262. Schultz, T.W., Netzeva, T.I., Roberts, D.W. and Cronin, M.T.D. 2005. Structure-toxicity relationships for carbonyl-containing a,b-unsaturated aliphatic chemicals evaluated with Tetrahymena pyriformis. Chemical Research in Toxicology 18: 330-341. Netzeva, T.I., Worth, A.P., Aldenberg, T. Benigni, R. Cronin, M.T.D., Gramatica, P., Jaworska, J.S., Klopman, G. Marchant, C.A., Myatt, G., Nikolova-Jeliazkova, N., Patlewicz, G.Y., Perkins, R. Roberts, D.W., Schultz, T.W., Stanton, D.T., van de Sandt, J.J.M., Tong, W. Veith, G.D. and Yang, C. 2005. Current status of methods for defining the applicability domain of (quantitative) structure-activity relationships: The report and recommendations of ECVAM workshop 52. Alternatives to Laboratory Animals 33: 155-173. Aptula, A.O., Jeliazkova, N.G., Schultz, T.W. and Cronin, M.T.D. 2005. The better predictive model: High q2 for the training set or low root mean square error of prediction for the test set? QSAR and Combinatorial Sciences 24: 385-396. Sanseverino, J., Saidak, L., Gupta, R.K., Layton, A.C., Patterson, S.S., Ripp, S., Simpson, M.L., Schultz, T.W. and Sayler, G.S. 2005. Saccharomyces cerevisiae BLYES expressing bacterial bioluminescence for rapid, sensitive detection of estrogenic compounds. Applied and Environmental Microbiology 71: 4455-4460. Aptula, A.O., Roberts, D.W., Cronin, M.T.D. and Schultz, T.W. 2005. Chemistry-toxicity relationships for the effects of di- and tri-hydroxybenzenes to Tetrahymena pyriformis. Chemical Research in Toxicology 18: 844-854. Hansen, L,. Machela, M., Fischer, L. James, M. Henning, J.B., Glauert, H., Narbonne, J.-F., van Bree, L., Schultz, T.W., Grevatt, P. Suk, W., Holoubek, I., Robertson, L. 2005. Research needs identified at the Second PCB Workshop in Brno, Czech Republic, May 7–11, 2002. Toxicological & Environmental Chemistry 87: 261–265.


Schultz, T.W., Yarbrough, J.W. and Johnson, E.L. 2005. Structure-activity relationships for glutathione reactivity of carbonyl-containing compounds. SAR QSAR in Environmental Research 16: 313-322. Schultz, T.W., Yarbrough, J.W. and Woldemeskel, M. 2005. Toxicity to Tetrahymena and abiotic thiol reactivity of aromatic isothiocyanates. Cell Biology and Toxicology 21: 181-189. Netzeva, T.I., and Schultz, T.W. 2005. QSARs for the aquatic toxicity of aromatic aldehydes from Tetrahymena data. Chemosphere 61: 1632-1643. Yarbrough, J.W., Woldemeskel, M., Cronin, M.T.D. and Schultz, T.W. 2005. Structure-toxicity relationships for a,b-unsaturated carbonyl substituted compounds: Quantifying molecular reactivity. Presented at ADEMT-2. San Diego, California. Schultz, T.W. 2005. Chemical reactivity with model nucleophiles: Predicting skin sensitization and respiratory irritation. Presented at Presented at the Society of Chemical Industry meeting on “In Silico Design of Bioactive Compounds: Absorption, Distribution, Metabolism, Excretion and Toxicity.” London, United Kingdom. Sanseverino, J., Layton, A.C., Easter, J.P., Menn, F-M., Saidak, L., Garrett, V., Schultz, T.W. and Sayler, G.S. 2005. A bioluminescent estrogen yeast-reporter system for determining estrogenic activity. Presented at the 105th Meeting of the American Society for Microbiology. Atlanta, Georgia. Schultz. T.W., Woldemeskel, M. and Cronin, M.T.D. 2005. The role of electrophilic reactivity in Quantitative Structure-Activity Relationships (QSARs) for toxicity. Presented at 5th World Congress on Alternatives & Animal Use in the Life Sciences. Berlin, Germany. Veith, G.D., Cronin, M.T.D. and Schultz, T.W. 2005. Developing a framework to predict the toxicity of electrophiles: Findings of an expert panel. Presented at 5th World Congress on Alternatives & Animal Use in the Life Sciences. Berlin, Germany. Schultz, T.W. 2005. Applications of consensus modeling: Observation on phenol toxicity. Presented at Consultation Meeting on Consensus Modelling and Battery approaches in (Q)SAR. Ispra, Italy. Pamela L.C. Small Adusumilli S, Mve-Obiang A, Sparer T, Meyers W, Hayman J, Small PLC. 2005. Mycobacterium ulcerans toxic macrolide, moycolactone modulates the host immune response and cellular location of M. ulcerans in vitro and in vivo. Cell Microbiol. 7(9): 1295-304.


Coutanceau E, Marsollier L, Brosch R, Perret E, Goossens P, Tanguy M, Cole ST, Small PLC, Memangel C. 2005. Modulation of the host immune response by a transient intracellular stage of Mycobacterium ulcerans: the contribution of endogenous mycolactone toxin. Cell Microbiol. 7(8): 1187-96. Marsollier L, Aubry J, Coutanceau E, Andre JP, Small PLC, Milon G, Legras P, Guadagnini S, Cargonnelle B, Cole ST. 2005. Colonization of the salivary glands of Naucoris cimicoides by Mycobacterium ulcerans requires host plasmatocytes and a macrolide toxin, mycolactone. Cell Microbiol. 7(7): 935-43. Johnson PD, Stinear T, Small PLC, Pluschke G, Merritt RW, Portaels F, Huygen K, Hayman JA, Asiedu K. 2005. Buruli ulcer (M ulcerans infection): new insights, new hope for disease control. PLoS Med. 2(4):e108. Judd TC, Bischoff A, Kishi Y, Adusumilli S, Small PLC. 2004. Structure determination of mycolactone C via total synthesis. Org Letters 6(26): 4901-4. Patricia Tithof Mancuso, P, Canetti, C, Gottschalk A, Tithof PK, Peters-Golden M. 2004. Leptin augments alveolar macrophage leukotriene synthesis by increasing phospholipase activity and enhancing Group IVC iPLA2 (cPLA2) protein expression. Am J. Physiol. Lung Cell. Mol. Physiol. 287(3): L497-L502. Martinez JM, Baek SJ, Mays DM, Tithof PK, Eling TE, Walker, NJ. 2004. EGR1 is a novel target for AhR agonists in human lung epithelial cells. Toxicol. Sci. 82(2): 429-435. Kim JH, Yamaguchi K, Lee SH, Tithof PK, Sayler GS, Yoon JH, Baek SJ. 2005. Evaluation of polycyclic aromatic hydrocarbons of early growth response-1 and peroxisome proliferator activated receptors. Toxicol. Sci. Epub ahead of print. Hwa-Chain Robert Wang Song, P. and Wang, H-C.R. 2004. Efficient Identification of TetR-Expressed Cell Lines for Tetracycline-Regulated Gene Expression. Electronic Journal of Biotechnology 7(2): 210-213. Song, P., Wei, J., Plummer III, H., and Wang, H-C.R. 2004. Potentiated caspase-3 in ras-transformed 10T1/2 cells. Biochemical and Biophysical Research Communications 322:557-564. Song, P., Wei, J., and Wang, H-C.R. 2005. Distinct roles of the ERK pathway in modulating apoptosis of Ras-transformed and non-transformed cells induced by anticancer agent FR901228. FEBS Letters: 579:90-94.


Ping Song, Jinxiong Wei, Yongfang Chan, Shambhunath Choudhory, and Hwa-Chain Robert Wang. 2005. Pro-apoptotic activity of oncogenic Ras facilitating the induction of apoptosis by a selective anticancer depsipeptide FR901228. Genome Science & Technology Graduate Program Retreat, The University of Tennessee/Oak Ridge National Laboratory. Jinxiong Wei, Cunge Zhang, Ping Song, Yongfang Chen, and Hwa-Chain Robert Wang. 2005. Molecular potency of tobacco carcinogens NNK and B[a]P in the transformation of human breast epithelial cells to cancerous cells. Genome Science & Technology Graduate Program Retreat, The University of Tennessee/Oak Ridge National Laboratory. Song, P., Wei, JX and Wang, H-C.R. 2005. Pathways potentiated by oncogenic Ras to modulate apoptosis induced by anticancer agent FR901228. Proceedings of the American Association for Cancer Research, Abstract # 4121. Wei, JX, Zhang, C., Chen, YF, Song, P. and Wang, H-C.R. 2005. Potency and signatures of tobacco carcinogens NNK and B[a]P in the development of human breast cancer cells. Proceedings of the American Association for Cancer Research, Abstract #3905. The Chinese American Academic and Professional Association in Southeastern United States. Genes, Signals, Cells, and Cancer Prevention and Treatment. Atlanta, GA, June 25, 2005. China Agricultural University, College of Veterinary Medicine. Clinical Services and Cancer Research at the University of Tennessee CVM. Beijing, China, September 1, 2004. Peking University. Signatures of oncogene- and carcinogen-induced cancer cells for anticancer targets. Beijing, China, September 2, 2004. Institute of Biomedical Sciences, Academia Sinica. Pathways potentiated by oncogenic Ras to facilitate apoptosis induced by anticancer agent. Taipei, Taiwan, September 6, 2004. National Yang-Ming University. Proapoptosis of oncogenic Ras to anticancer agent FR901228. Taipei, Taiwan, September 7, 2004. Institute of Zoological Sciences, Academia Sinica. Proapoptotic pathways activated by oncogenic Ras to anticancer agent. Taipei, Taiwan, September 9, 2004. Xuemin Xu Guojun Zhao, Mei-Zhen Cui, Guozhang Mao, Jianxin Tan, Yunzhou Dong, Seong-Hun Kim and Xuemin Xu. 2004. Identification of a New Presenilin-dependent z-Cleavage Site within the Transmembrane Domain of Amyloid Precursor Protein. J. Biol. Chem. 279(49): 50647-50650.


Guojun Zhao, Mei-Zhen Cui, Guozhang Mao, Jianxin Tan, Yunzhou Dong, Longsheng Sun, and Xuemin Xu. 2005. γ-cleavage is dependent on ζ-cleavage during the proteolytic processing of amyloid precursor protein within its transmembrane domain. J. Biol. Chem., 2005. 280(45: 37689-37697. Yunzhou Dong, Jianxin Tan, Mei-Zhen Cui, Guojun Zhao, Guozhang Mao, Neena Singh, and Xuemin Xu. 2005. Calpain inhibitor MDL28170 modulates Ab formation by inhibiting the formation of intermediate Ab46 and protecting Ab from degradation. FASEB J. 2006 Feb;20(2):331-3. Epub. A novel zeta-cleavage site at Ab46 and its role in the formation of secreted Ab40/42. Site: 3rd Beijing International Symposium on Neurodegenerative Disease and Stroke (Beijing, China, 2005), Served as Chair on Alzheimer’s Disease section. γ-cleavage is dependent on ζ-cleavage during a sequential proteolytic processing of amyloid precursor protein within its transmembrane domain. Society for Neuroscience, 35th Annual Meeting (2005) Washington, DC.

Research Funded Externally - Detail

Project Director Title of Grant Funding Agency Total Award Expenditures 05

Seung Joon Baek Regulation and Biological Function of NAG-1

National Institutes of Health

$324,000 9/1/03 - 6/30/06

$108,940

Anti-Cancer Effects by Green Tea Catechins


$342,452 4/6/05 - 3/31/07

$18,598

David Brian Mechanisms of Coronavirus RNA Amplification


$1,742,401 6/15/02 - 5/31/07

$367,686

Mei-Zhen Cui Lysophosphatidic Acid & Tissue Factor in Atherosclerosis


$1,002,400 6/1/04 - 4/30/08

$247,812

Role of Lysophosphatidic Acid and Other Lipid Peroxidation Products in Smoking-Induced Atherothrombosis

Philip Morris, Inc. $547,397 6/1/04 - 6/30/07

$150,041

Lysophosphatidic Acid Induction of Tissue Factor Gene Expression in Vascular Smooth Muscle Cells

American Heart Asso-ciation

$154,000 6/1/03 - 630/05

$75,622

Lysophosphatidic Acid Regulation of Transcription Factor EGR-1 in Vascular Smooth Muscle

Pfizer $100,000 7/1/02 - 6/30/05

$23,324

Stephen Kania Development of an Improved Test for Bovine Spongiform Encephalopathy

Mont-Vue Farms $50,000 8/3/04 - 2/1/06

$42,772



Michael McEntee Murine Intestinal Tumorigenesis and Pathology


$485,024 6/3/01 - 5/31/06

$99,488

Stephen Oliver Bovine Mastitis

Research Pfizer $130,500

7/1/04 - 12/31/05 $15,234

Recurrent Coliform

Mastitis in New York Dairy Cows

Cornell University $99,922 7/1/03 - 12/5/04

$52,781

Milk Residue Study East TN Clinical Re-

search Initiative $16,705

1/1/04 -12/31/04 $0

Role of Streptococ-

cus uberis Adhesion (SUAM) Molecule in the Pathogenesis of Bovine Mastitis

USDA $341,879 6/1/04 - 7/31/07

$39,362

Streptococcus

uberis Adhesion Molecule

Private $15,050 1/1/04 - 12/15/05

$8,077

Gina Pighetti Leptin Regulation of

Mammary Cell Growth

U.S. Army $65,011 12/5/01 - 12/5/04

$11,714

Evaluating a Novel

Gene Marker for its Association with Susceptibility to Bovine Mastitis

Merial $54,397 3/1/04 - 2/28/06

$8,351

H. Plummer, III GIRK Channels,

Beta-Adrenergic Signaling and Breast Cancer

Philip Morris, Inc. $752,989 6/1/04 -6/30/07

$158,661

Barry Rouse Immunity

Mechanisms in Herpes Virus Infections


$1,656,250 1/1/01 -12/31/05

$317,227



Barry Rouse

Mechanisms of Herpetic Keratitis


$1,779,700 9/1/02 - 9/29/07

$259,659

Vaccination Against

Herpes Simplex Virus


$1,423,760 1/1/01 - 12/31/05

$256,321

Hildegard Schuller Transplacental

Pancreatic Carcinogenesis by NNK


$1,158,400 4/1/03 - 3/31/07

$310,013

Preclinical Model for

Chemoprevention of NSCLC in Former Smokers


$868,800 5/1/03/ - 4/30/06

$218,768

NNK, Beta-

Adrenergic AA Releases, and Lung Cancer


$1,142,201 4/1/02 - 3/31/06

$255,301

New Radiotracers

for Targeting Mutated Protein for the Early Detection of Lung Cancer

Department of Energy $181,325 8/15/04 - 8/14/07

$53,611

Terry Schultz Biosurvelliance,

Agricultural and Environmental Security: A Coordinated, Innovative Approach

Department of Defense $1,977,131 6/1/04 - 6/30/06

$167,236

Bioluminescent

Yeast-Reporter System for Screening Chemicals for Estrogenic and Androgenic Effects

EPA $45,531 10/1/03 - 9/30/06

$5,387



Pamela L.C. Small Mycolactone-Mediated Virulence in M. ulcerans


$1,194,750 1/1/01 - 2/28/06

$270,437

Investigations into

the Role of Aquatic Reservoirs in the Transmission of Buruli Ulcer

World Health Organization

$41,570 6/1/05 - 5/31/06

$17,506

Hwa-Chain Robert Wang

Potency and Molecular Signatures of Tobacco Carcinogens in the Early Development of Human Breast Cancer

Philip Morris, Inc. $659,320 7/1/03 - 6/30/06

$210,344

Signaling Pathway

in Modulation of Cell Quiescence

National Science Foundation

$100,000 6/1/05 - 5/31/07

$0

Xuemin Xu Role of a Novel

Protein (PSAP) in Neurodegeneration


$1,282,500 9/1/01 - 8/31/05

$292,439

Total $19,735,365 $4,062,712

Center Budget - Schedule 7

CENTERS OF EXCELLENCE/CENTERS OF EMPHASIS

ACTUAL, PROPOSED, AND REQUESTED BUDGET

Institution: College of Veterinary Medicine Center: COE in Livestock Disease & Human Health

FY 2004-05 Actual FY 2005-06 Proposed FY 2006-07 Requested

Matching Appropr. Total Matching Appropr. Total Matching Appropr. Total

Expenditures 0 0 0

Salaries

Faculty 26,577 53,154 79,731 26,134 52,268 78,402 27,441 54,881 82,322

Other Professional 91,290 182,581 273,871 58,033 116,065 174,098 60,935 121,868 182,803

Clerical/ Supporting 28,154 56,308 84,462 9,124 18,249 27,373 9,580 19,161 28,741

Assistantships 24,999 49,999 74,998 21,305 42,609 63,914 22,370 44,739 67,109

Total Salaries 171,020 342,042 513,062 114,596 229,191 343,787 120,326 240,651 360,977

Longevity 1,689 3,379 5,068 1,131 2,262 3,393 1,188 2,375 3,563

Fringe Benefits 38,983 77,966 116,949 34,004 68,008 102,012 35,704 71,408 107,112

Total Personnel 211,692 423,387 635,079 149,731 299,461 449,192 157,218 314,434 471,652

Non-Personnel

Travel 2,708 5,417 8,125 6,665 13,330 19,995 6,998 13,997 20,995

Software 0 0 0

Books & Journals 66 133 199 333 667 1,000 350 700 1,050

Other Supplies 22,386 44,773 67,159 132,315 264,624 396,939 89,271 178,541 267,812

Equipment 14,616 29,233 43,849 3,333 6,667 10,000 3,500 7,000 10,500

Maintenance 13,640 27,279 40,919 12,085 24,169 36,254 12,689 25,377 38,066

Scholarships 1,450 2,900 4,350 5,333 10,667 16,000 5,600 11,200 16,800

Consultants 0 0 0

Renovation 0 0 0

Other (Specify) 0 0 0

Print/Pub/Postage/Frght/ Publicity/Comp Svc/Rental/ Ins/Grp Food & Lodging/ Conference Registration

4,348 8,696 13,044 0 0

Services 7,437 14,874 22,311 0 0

Total Non-Personnel 72,968 145,939 218,907 160,064 320,124 480,188 118,407 236,815 355,223

GRAND TOTAL 284,660 569,326 853,986 309,795 619,585 929,380 275,625 551,250 826,875

Revenue

New State Appropriation 514,600 514,600 525,000 525,000 551,250 551,250

Carryover State Appropriation 149,311 149,311 94,585 94,585 0

New Matching Funds 257,300 257,300 262,500 262,500 275,625 275,625

Carryover from Previous Matching Funds 74,665 74,665 47,295 47,295 0

Total Revenue 331,965 663,911 995,876 309,795 619,585 929,380 275,625 551,250 826,875

coe in livestock diseases and human health 2001-2005

Documents