March 2012

Pioneering Research in Proteomics

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Richard R. Drake, PhD, one of the nation’s leading experts on the complex role of proteins in the development of cancer, serves as the Medical University of South Carolina (MUSC) SmartState Endowed Chair in Proteomics. Drake, a professor in the Department of Cell and Molecular Pharmacology and Experimental Therapeutics, was appointed director of MUSC’s Proteomics Center. Proteomics is the study of all the proteins present in a cell, tissue or organism at any moment. The human body contains millions of proteins, all of them with distinct functions that drive activity in and between cells. Whereas the specific components of any individual genome may be somewhat fixed, protein expression and behavior is remarkably dynamic in reflecting the biology of cells and tissue. By defining these protein changes in combination with clinical information, protein “biomarker” tests can be developed that lead to more personalized protocols and treatments for patients. Dr. Drake’s research efforts focus on the use of mass spectrometry for proteomic, glycomic and tissue imaging approaches for cancer biomarker discovery and diagnostic assay development. The Mass Spectrometry Facility is housed within the Department of Pharmacology and directed by Dr. Lauren Ball. It serves as a university research resource facility and as a component of the Proteomics Center. New cutting edge mass

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spectrometry instrumentation will be installed this Spring, significantly expanding the already extensive infrastructure and resources of the Mass Spectrometry Facility

and MUSC Protemics Center. Dr. Stephen Lanier hopes, “the MUSC Proteomics Center will translate the research of Drake and his team into commercialized biomarker tests for a variety of medical fields.” Currently, Dr.

Drake’s research is focusing on prostate, renal, colon and breast cancers. Recent projects involve the characterization of the glycan structures on prostate specific antigen and prostatic acid phosphatase isolated from prostatic fluids reflective of prostatic disease state. Another project is using lectins to fractionate the complex proteomes of the clinical fluids prior to high-throughput expression profiling studies on the MALDI-TOF instruments, and deeper proteomic mining strategies on electrospray ion trap instruments. A third approach involves the use of metabolic labeling of tumor cell lines with modified sugar residues to identify candidate surface and secreted glycoproteins involved in cancer metastasis or drug responses. Lastly, a new research focal area is the use of MALDI-TOF mass spectrometry imaging of prostate cancer and renal carcinoma tissue samples. This latter area will be one of significant expansion at MUSC after installation of new instrumentation, and will be applicable to many types of cancer and other diseases.

Research INKlings

Research INKlings is an on-line monthly newsletter prepared by the Office of Research Development providing research news, policy changes and other relevant information for MUSC faculty, staff and students.

Inside this Issue

P2 Mobile Technologies Advance Clinical Research

P2 Mobile Health Technology Retreat

P3 Mobile Technologies Continued

P3 NIH Salary Cap Reduction

P3 Proposed National Institute of Substance Use and Addiction Disorders

P4 Grantsmanship Workshops

P4 SCTR Voucher Program

P4 Proteogenomics Facility

Dr. Lauren Ball and Dr. Richard Drake

Research Inklings Page 2

Mobile Health Technology Retreat The South Carolina Clinical & Translational Research Institute (SCTR) is sponsoring a Scientific Retreat focused on ‘Mobile Health Technologies’ at MUSC’s Bioengineering Building on Thursday April 26, 2012. The keynote speaker will be Dr. Wendy Nilson, Chair of the NIH's Mobile Health Training Institute. The primary purpose of the retreat is to stimulate new collaborative research projects across many disciplines and among the community of health professionals researchers, including basic scientists, clinicians, and nurses that would lead to productive pre-clinical, clinical and translational research. In addition, time will be allotted for group discussions and networking to develop potential collaborations including SCTR Institute pilot project initiatives for the 2012-2013 funding cycle. The agenda and the schedule of talks will be available by early April. Please register for the retreat by clicking here or contact Dayan Ranwala, PhD, SCTR Science Program Manager if you need more information at ranwala@musc.edu or 843-792-1498.

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The Technology Applications Center to Advance Healthful Lifestyles (TACHL) was launched a little over 14 months ago when Dr. Frank Treiber, Professor of Nursing and Psychiatry joined MUSC. TACHL's research program, led by postdoctoral research fellow, Dr. Mat Gregoski, has already produced several proof-of-concept clinical trials using mobile technologies as intervention delivery and monitoring mechanisms for the prevention and management of various chronic diseases that have an impact throughout South Carolina. These studies include HIV positive pediatric patients, prehypertensive youth and adults, uncontrolled adult hypertensives, type 2 diabetics, and kidney transplant patients who often have hypertension and/or type 2 diabetes. The various clinical research projects utilize smart phones as vehicles for real time bio data signal transfer from patients' bluetoothed medical devices (e.g., blood pressure/heart rate, glucose, oxygen saturations, weight) to secure server files for processing. Feedback is provided to healthcare providers and patients as to their progress. Figure 1 (placement of index finger with Droid device) and Figure 2 (placement of Droid and Nonin devices during data acquisition) show several of the medical devices being used. The smart phones are also being used to monitor patients' cognitive functions and emotional states and to implement cognitive behavioral interventions for prevention or treatment of chronic diseases. One of the methods involves using breathing meditation to reduce stress and blood pressure levels in prehypertensive adults. The use of a smart phone embedded heart rate monitoring system and auditory delivery of meditation instructions with immediate feedback graphs and motivational messages have been very successful in reducing blood pressure levels at rest and in the natural environment. This smart phone application is seen as a potential adjunct therapy for other diseases in which stress plays a contributory role. Embedded software applications are also

Mobile Technologies Advance Clinical Research

Research Inklings Page 3

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being developed enabling delivery of cognitive behavioral interventions (e.g., motivation therapy, self management skills enhancement, behavioral activation therapy) for enhancement of patient self-efficacy in managing their healthcare regimens. Working with various healthcare teams and clinician scientists, Drs. Gregoski and Treiber already have three peer-reviewed publications and several extramural grant applications under review. TACHL 's activities have caught the eye of Verizon, which is in negotiations with MUSC to establish a partnership where MUSC will be a beta test center for their nationwide healthcare platform initiative. The Technology Applications Center to Advance Healthful Lifestyles (TACHL) is a collaborate effort between MUSC and the University of South Carolina (USC) funded by the South Carolina Centers of Economic Excellence program.

Proposed National Institute of Substance Use and Addiction Disorders Recently, NIH published a request for input (RFI) into the development of the Scientific Strategic Plan for a proposed new institute. NIH proposes to create a new institute, with the working name of the National Institute of Substance Use and Addiction Disorders, through inclusion in the President’s budget for fiscal year 2014. A planning committee that includes scientific representatives from the potentially affected institutes and centers is developing a Scientific Strategic Plan for the proposed institute. The primary goal is to identify new scientific opportunities that are not currently supported in the existing NIH research portfolios, along with public health initiatives on substance use, abuse, and addiction related disorders. This proposal flows from the recommendation made by the Scientific Management Review Board in the fall of 2010 that all addiction related research throughout the NIH be consolidated under this new institute. As a result the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism will be dissolved, and their non-addiction research portfolios will be redistributed accordingly to other institutes and centers. This RFI is soliciting input on the scientific opportunities and public health needs that should be included in the Scientific Strategic Plan. They are not currently seeking input on the recommendation to create the new institute itself. Comments may be submitted here through May 11, 2012.

Mobile Technologies Continued from page 2

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NIH Salary Cap Reduction The FY2012 salary cap applies to ALL agencies under HHS except FDA (funded via

USDA) and the Indian Health Service. This is notable as in past fiscal years only NIH, AHRQ and SAMHSA were affected by the salary cap. All references to FY2012 below constitute the federal fiscal year. The bullet points below are based on the NIH guidance as NIH funding makes up the bulk of MUSC’s research funding. The initial issue date of the FY2012 increment of the grant award is the determinant of which federal fiscal year NIH salary is applicable.

• The implementation of the new lower salary cap ($179,700) is effective on FY 2012 awards where the initial issue date of the award is on/after 12/23/2011. For FY2012 awards issued on/before December 22, 2011 (competing and non-competing), the effective salary cap remains at the Executive Level I ($199,700).

• If a grant award was issued on/after December 23, 2011 and it is a non-competing award, then grantees may re-budget the funds awarded in excess of the new salary limit. However, if the grant is a competing award, the NIH will revise the award when an adjustment for the lower salary limit is needed.

• Any grants awarded in previous fiscal years are not impacted by the FY 2012 salary limitation. Carrying over previous federal fiscal years’ funds to support salaries will remain at the salary limitation levels in effect at the time those awards were issued.

• Salary limitation does NOT apply to payments made to consultants under an NIH grant or contract.

• Salary limitation provision DOES apply to subawards/subcontracts for substantive work under an NIH grant or contract.

As more information becomes available on this significant salary cap change it will be posted on the ORSP web page for reference as soon as possible. Should anyone have questions/concerns about this information, PLEASE contact the Office of Research and Sponsored Programs at 792-3838 or at orsp@musc.edu.

Research inklings March 2012

Grantsmanship Workshops On February 28-29, MUSC’s Office of Research Development conducted its Grantsmanship Consultations and Workshop. Lead by Dr. Israel Goldberg, president of Health Research Associates, the Grantsmanship Workshops are interactive lectures covering the NIH organization, peer review system, and the ABC’s of grant proposals. Dr. Goldberg’s workshop entitled, “Your Research Career Development Grant Proposal—Who, When, and How?” concentrated on the NIH Mentored Research Career Development K-grant mechanisms, focusing on who should (and who should not) apply; what does (and what does not) work; and how to write for the reviewers. The workshop was held in Bioengineering Classroom 112, and attended by approximately 75 faculty, staff, and students. In addition to the workshops, Dr. Goldberg provided junior and senior investigators, as well as collaborative teams with independent feedback regarding their R01, R21, and career development proposals. During these, 45-minute meetings, Dr. Goldberg evaluated summary statements and discussed developing a strategy for revising and resubmitting their proposal. To suggest topics for upcoming research education and training workshops, please contact Wanda Hutto, Research Development at huttow@musc.edu.

SCTR Voucher Program Continues

The South Carolina Clinical & Translational Research (SCTR) Institute’s Voucher Program is an ongoing funding opportunity. SCTR vouchers enable MUSC investigators to gather preliminary data for inclusion in a grant proposal, improve the science or safety of their research projects, or develop a translational focus to their research. To support as many researchers as possible, a policy change for 2012 the voucher program stipulates, that per approved protocol, only one voucher per PI, per year will be granted for up to $1,000 for research services and supplies. For more information about the SCTR Voucher Program, please contact the SUCCESS center at success@musc.edu.

Proteogenomics Facility Introduces Next-gen Sequencing at MUSC The MUSC Proteogenomics Facility is pleased to unveil its new next generation (next-gen) sequencing instrumentation, a Life Technologies Ion Torrent Personal Genome Machine (PGM). Acquired with institutional support and extramural funds from the NIH-funded COBRE for Cardiovascular Disease and the NSF-funded SC Project for Organ Biofabrication, the Ion PGM is the first next-gen instrument at MUSC, and the first Ion PGM in South Carolina. Remarkable because of its innovative sequencing chemistry, Ion Torrent replaces the more traditional fluorescence detection methods with semiconductor-based detection, translating the chemical signal associated with base additions into digital information. The resulting instrument operates appreciably faster than traditional sequencing platforms, and is scalable in terms of read-length and sequencing depth. Dr. Scott Argraves, Director of the Facility, expects that next-gen sequencing service with the Ion PGM will dovetail with the broader genomic initiatives at MUSC, providing a flexible platform for a broad range of next-gen sequencing applications, and serving investigators with rigorous sequencing needs while also accommodating those preferring a measured entry into the next-gen sequencing arena. Well suited to mid-range sequencing applications, the Ion PGM can be used for small genomes, deep sequencing of gene sets or enriched genomic content, ChIP-Seq, miRNA-Seq, and targeted RNA-Seq. The instrument has a rapid run time (90-minute for 100-base sequencing runs) and a current estimated output of 10 Mb to 1Gb per run, depending on the sequencing chip format used. Investigators interested in seeking service or in discussing potential sequencing applications should contact Dr. Jeremy (Jamie) Barth (barthj@musc.edu; 843-792-9984).

Dr. Scott Argraves (right) and Dr. Jeremy Barth (left)

NIH CENTERS OF BIOMEDICAL RESEARCH EXCELLENCE (COBRE) PROGRAM - CALL FOR CONCEPT PAPERS For more information, please contact Dr. Joann Sullivan at sullivan@musc.edu.