Genomic Pathology:Genomic Pathology:One Gene, One Disease, One MedicineOne Gene, One Disease, One Medicine

Robert D. Cardiff, M.D., Ph.D.Robert D. Cardiff, M.D., Ph.D.DirectorDirector

Center for Genomic PathologyCenter for Genomic PathologyCenter for Comparative MedicineCenter for Comparative Medicine

Department of Pathology and Laboratory MedicineDepartment of Pathology and Laboratory MedicineUniversity of California, DavisUniversity of California, Davis

http://ctrgenpath.orghttp://ctrgenpath.org

Gene-Specific Breast Cancer Phenotypes

ras myc neu

GEM PROSTATE TUMORSGEM PROSTATE TUMORSThat Mimic HumanThat Mimic Human

WHICH IS HUMAN?A or B?

A B

Elwood-Yen PMID 14522256

SPONTANEOUSHUMAN

Induced byMYC

Genomic Medicine Genomic Medicine

1.1. The human genome is sequencedThe human genome is sequencedThe genetic code has been “broken”The genetic code has been “broken”

2.2. The function of each gene will be The function of each gene will be determined by phenotyping determined by phenotyping

(Phenogenomics)(Phenogenomics)

3.3. The phenotypes will be ‘induced’ in The phenotypes will be ‘induced’ in Genetically Engineered Mice (GEM)Genetically Engineered Mice (GEM)

The mouse is a powerful model for The mouse is a powerful model for human genomicshuman genomics

Genomics will revolutionize medicine.Genomics will revolutionize medicine.

Mouse mutants provide the most Mouse mutants provide the most durable and high throughput means durable and high throughput means of understanding human genomic of understanding human genomic biology.biology.

Mouse models represent the virtual Mouse models represent the virtual “Koch’s Postulates” of modern “Koch’s Postulates” of modern biology.biology.

The genome has been sequenced.The genome has been sequenced. The function of each gene needs to be elucidated by The function of each gene needs to be elucidated by

phenotyping. phenotyping. (Phenogenomics)(Phenogenomics)

Genes are associated with diseases. Diseases require Genes are associated with diseases. Diseases require microscopic microscopic validationvalidation. .

(Genomic Pathology)(Genomic Pathology)

Gene phenotyping starts with the mouse, analyzed by Gene phenotyping starts with the mouse, analyzed by Genomic PathologistsGenomic Pathologists..

What is Genomic Pathology?What is Genomic Pathology?

Far too many devastating, costly errors in the literature!

The Impending CrisisThe Impending Crisis

Industry, NIH and other international Industry, NIH and other international agencies are generating huge agencies are generating huge numbers of genetically modified mice. numbers of genetically modified mice. (20,000 -200,000 new (20,000 -200,000 new strainsstrains))

Mouse mutant phenotypes are often Mouse mutant phenotypes are often inadequately characterized or inadequately characterized or misinterpreted.misinterpreted.

Not enough existing comparative Not enough existing comparative pathologists to meet this need.pathologists to meet this need.

Documenting the critical shortageDocumenting the critical shortage

The PRIME and ACVP reportsThe PRIME and ACVP reports– Few experimental mouse Few experimental mouse

pathologistspathologists– Few experienced with multiple Few experienced with multiple

mouse lines.mouse lines.– Necropsies often done without Necropsies often done without

benefit of trained pathologists.benefit of trained pathologists.– Workers often lack appropriate Workers often lack appropriate

qualifications.qualifications.

The Solution:The Solution:

A coordinated system to share information and A coordinated system to share information and access available comparative pathology resources.access available comparative pathology resources.

A world-class facultyA world-class faculty

Streamlined interactive training of future Streamlined interactive training of future generations of comparative pathologists. generations of comparative pathologists.

Proper training of all levels of “parapathologists”.Proper training of all levels of “parapathologists”.

Economical Web-based training programsEconomical Web-based training programs

Proper certification of Trainees.Proper certification of Trainees.

How do I Learn aboutHow do I Learn aboutGenomic Pathology?Genomic Pathology?

http://ctrgenpath.net

““GENOMIC PATHOLOGY”GENOMIC PATHOLOGY”Divisions of Course WorkDivisions of Course Work

offered over the Internetoffered over the Internet

LEVEL ONE: BIOLOGY OF LABORATORY MICELEVEL ONE: BIOLOGY OF LABORATORY MICE– DESIGNEDDESIGNED For graduate students, fellows and technical staff For graduate students, fellows and technical staff– GOAL:GOAL: To train the student to more effectively and accurately To train the student to more effectively and accurately

perform studies using a mouse model. Emphasis on identification of perform studies using a mouse model. Emphasis on identification of gross and microscopic features of the healthy and diseased animalsgross and microscopic features of the healthy and diseased animals

LEVEL TWO: PATHOLOGY OF GENETIC ENGINEERED MICE LEVEL TWO: PATHOLOGY OF GENETIC ENGINEERED MICE (GEM)(GEM)– DESIGNEDDESIGNED For persons with advanced degrees and Level I graduates For persons with advanced degrees and Level I graduates– GOALGOAL: To provide training in the biology and pathology of GEM for PIs.: To provide training in the biology and pathology of GEM for PIs.

LEVEL THREE: ADVANCED STUDIES OF GEMLEVEL THREE: ADVANCED STUDIES OF GEM– DESIGNEDDESIGNED For certified veterinary and medical pathologists For certified veterinary and medical pathologists

who desire advanced study on GEMwho desire advanced study on GEM– GOAL:GOAL: To provide graduate information on specific pathologic To provide graduate information on specific pathologic

changes seen in many GEM strains. To prepare the pathologist to changes seen in many GEM strains. To prepare the pathologist to become competent in evaluating these unique changes both gross and become competent in evaluating these unique changes both gross and microscopically. microscopically.

CGP FacultyCGP Faculty James M. CrawfordJames M. Crawford, M.D., Ph.D. Chairman of Pathology and , M.D., Ph.D. Chairman of Pathology and

Editor in Chief Lab Investigation (229 PubMed publications) Editor in Chief Lab Investigation (229 PubMed publications) Stephen W. BartholdStephen W. Barthold, D.V.M.. Ph.D. Professor and Director, , D.V.M.. Ph.D. Professor and Director,

Member NAS (211 PubMed publications), Co-author Percy Member NAS (211 PubMed publications), Co-author Percy and Barthold “Rodent Pathology”.and Barthold “Rodent Pathology”.

Rod BronsonRod Bronson, D.V.M. (471 PubMed publications), D.V.M. (471 PubMed publications) Robert D. CardiffRobert D. Cardiff, M.D., Ph.D., Distinguished Professor, , M.D., Ph.D., Distinguished Professor,

Former Chair of UCD Pathology, Former UCD Director of Former Chair of UCD Pathology, Former UCD Director of Medical Informatics AAAS Fellow (234 PubMed Medical Informatics AAAS Fellow (234 PubMed publications)publications)

Murray B. GardnerMurray B. Gardner, M.D., Professor Emeritus, Former Chair , M.D., Professor Emeritus, Former Chair UCD Pathology. AAAS Fellow (245 PubMed publications)UCD Pathology. AAAS Fellow (245 PubMed publications)

VE Ted ValliVE Ted Valli, D.V.M., M.Sc., Ph.D. Former Chair of , D.V.M., M.Sc., Ph.D. Former Chair of Pathology, Guelph, Former Dean Illinois College of Pathology, Guelph, Former Dean Illinois College of Veterinary Medicine (225 PubMed publications)Veterinary Medicine (225 PubMed publications)

Jerrold M. WardJerrold M. Ward, D.V.M., Ph.D. (566 PubMed publications), D.V.M., Ph.D. (566 PubMed publications) Robert R. MaronpotRobert R. Maronpot, D.V.M. (273 PubMed publications), D.V.M. (273 PubMed publications) See See http://ctrgenpath.nethttp://ctrgenpath.net for all CGP members for all CGP members

LEVEL ONELEVEL ONE

60+ Hours of PPT

http://ctrgenpath.net