Dr. Chinnaiyan is the S.P. Hicks Endowed Professor of Pathology and Professor of Pathology and Urology at the University of Michigan Medical School. He is an international leader in cancer genomics, biology, and bioinformatics. Dr. Chinnaiyan is a board certified Clinical Pathologist and serves as Director of the Division of Pathology Research Informatics and Director of Cancer Bioinformatics. In January of 2007, Dr. Chinnaiyan will be named the founding Director of the Michigan Center for Translational Pathology (MCTP).

Dr. Chinnaiyan was a fellow of the Medical Scientist Training Program (MSTP) at Michigan from 1992-1999. He received his Ph.D. in Pathology and has made seminal contributions to the understanding of the molecular mechanisms of apoptosis in the laboratory of Dr. Vishva Dixit. By performing a yeast two-hybrid screen using the cytoplasmic domain of CD95/Fas/APO-1, he helped clone and characterize FADD (Cell 81:505). A subsequent study revealed that FADD could directly engage the cell death machinery by interacting with and activating FLICE (FADD-like Interleukin-1beta Converting Enzyme, now known as caspase-8) (Cell 85:817). Taken together, this work helped define how cell death receptors engage the cytoplasmic cell death machinery. He co-authored over 20 publications during his graduate years- over half of which he was first author.

After completing his graduate thesis work, Dr. Chinnaiyan went on to complete his clinical training and received his M.D., Ph.D. degrees in 1999. He then joined the Clinical Pathology Residency Program at Michigan and under the guidance of then Chair of the Department, Dr. Peter Ward, he began to establish an independent laboratory (without formal post-doctoral training). In 2001, he was appointed as an Assistant Professor of Pathology.

Dr. Chinnaiyan's laboratory currently focuses on genomic, proteomic and bioinformatics approaches to study cancer progression for the purpose of identifying clinical biomarkers and novel therapeutic targets Prostate cancer has been the primary disease state of focus interest in the laboratory. One of the most important contributions from the Chinnaiyan lab was published in the October 2005 issue of the journal Science (310:644). In this study, his group used a bioinformatics approach to nominate oncogenes from the cancer microarray compendium called Oncomine. Interestingly this approach selected two genes of the ETS family of nuclear transcription factors, ERG and ETV1 as being candidate oncogenes in prostate cancer. They went on to sequence these cDNAs in human prostate cancer tissue specimens and to their surprise discovered that both the ERG and ETV1 genes were fused to the 5' untranslated region of TMPRSS2, a serine protease expressed in the prostate. By FISH analysis, in collaboration with Dr. Mark Rubin at the Brigham and Women's Hospital, they found that the majority of prostate cancers (upwards of 70%) harbor rearrangements of the ETS family causing aberrant fusion with the TMPRSS2 gene. Importantly, this fuses the androgen-responsive promoter elements of TMPRSS2 upstream of ERG or ETV-1 driving aberrant overexpression of these oncogenic transcription factors in prostate cancer.

Taken together, these findings provide compelling evidence that recurrent gene fusions of TMPRSS2 and ETS transcription factors may be the "causative" lesion in prostate cancer much as the BCR-ABL gene fusion has been implicated as the cause of chronic myelogenous leukemia (CML). In the case of CML, identification of the gene fusion led to the eventual development of a highly successful therapy, the drug called Gleevec. Likewise, ERG and ETV1 become rational targets for prostate cancer therapy and we hope, in the future, lead to new drugs for prostate cancer. In addition to being a therapeutic target in prostate cancer, these gene fusions become ideal diagnostic targets if they can be detected in urine or blood, since they are exquisitely specific to prostate cancer.

The identification of these recurrent gene fusions is not only important for understanding the genesis of prostate cancer, but also suggests that other common epithelial tumors such as breast, lung, and colon cancer arise from recurrent chromosomal gene fusions. Before this study, recurrent chromosomal rearrangements were almost exclusively limited to leukemias, lymphomas, and certain sarcomas. This is a paradigm-shift in the way we look at common carcinomas, which account for most of the morbidity and mortality due to cancer in the U.S.

In addition to the identification of a gene fusion/translocation in prostate cancer, Dr. Chinnaiyan's group has had a number of other important contributions including the observation linking the Polycomb Group Protein EZH2 to solid tumors (Nature 419: 624, PNAS 100:11606), autoantibody signatures of prostate cancer (NEJM 353:1224) and integrative molecular approaches to study molecular alterations in cancer (Cancer Cell 8:393, Nature Genetics 37:579). His group, along with others, was among the first to discover AMACR as a tissue biomarker of prostate cancer (JAMA, 287:1662) which is now being commonly used in the assessment of challenging prostate needle biopsies in GU pathology labs across the nation.