Arul Chinnaiyan, M.D., Ph.D.

Director, Michigan Center for Translational Pathology; S.P. Hicks Endowed Professor of Pathology; Investigator, Howard Hughes Medical Institute ; American Cancer Society Research Professor

Biography

Arul M. Chinnaiyan, M.D., Ph.D. is a Howard Hughes Medical Institute Investigator, American Cancer Society Research Professor, and S.P. Hicks Endowed Professor of Pathology and Urology at the University of Michigan. He also serves as the inaugural Director of the Michigan Center for Translational Pathology (MCTP) which is comprised of a multi-disciplinary team of investigators focused on translating “-Omic” technologies to patient care in terms of biomarkers and novel therapeutics. He has co-authored over 350 manuscripts and has been designated an A. Alfred Taubman Medical Research Institute Scholar and is an elected member of the American Academy of Arts and Sciences (AAAS), the Institute of Medicine (IOM) of the National Academy of Sciences, the Association of American Physicians (AAP) and the American Society for Clinical Investigation (ASCI). He serves on the Board of Scientific Advisors for the National Cancer Institute.

His group has characterized a number of important biomarkers of prostate cancer including AMACR, EZH2, the sarcosine metabolite, and most recently the long non-coding RNA (lncRNA) Schlap1. AMACR is being used clinically across the country in the assessment of cancer in prostate needle biopsies. His landmark study thus far is the discovery of TMPRSS2-ETS gene fusions in prostate cancer. TMPRSS2-ETS gene fusions are specific markers of prostate cancer as well as presumably function as rational targets for this disease. This finding potentially redefines the molecular basis of prostate cancer as well as other common epithelial cancers. Staining for the most common gene fusion product, TMPRSS2-ERG, is available in pathology laboratories for molecular subtyping of prostate cancer and the assessment of clinically challenging foci assessed by prostate needle biopsy. Since mid-2013, detection of TMPRSS2-ERG combined with the lncRNA PCA3 in urine (called the MiPS test) is available in CLIA reference laboratories for the detection of clinically significant prostate cancer (licensed and developed with Gen-Probe/Hologic). Currently he is looking for ways to target this gene fusion as well as discover similar gene fusions in other common epithelial tumors such as those derived from the breast, lung, and colon. Dr. Chinnaiyan also led the development of the popular cancer profiling bioinformatics resource called Oncomine (www.oncomine.org). Most recently, he has been involved in developing high-throughput clinical sequencing approaches for precision oncology (i.e., the MI-ONCOSEQ project). This has led to a number of discoveries including the pathognomomic gene fusion for solitary fibrous tumor (SFT), targetable FGFR kinase fusions across a diverse array of cancers, and mutations in ESR1 as a common resistance mechanism of endocrine therapy in breast cancer. More recently, a substantial portion of his lab is exploring RNA-seq methods to decipher the landscape of lncRNAs in cancer including in depth mechanistic and biomarker analyses of the lncRNAs Schalp1, PCAT1, PCAT29 and PCA3 among others.

Research Interests

Functional genomic, proteomic and bioinformatics approaches to study cancer and understand cancer biology as well as to discover clinical biomarkers

Publications

Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, Montgomery B, Taplin ME, Pritchard CC, Attard G, Beltran H, Abida W, Bradley RK, Vinson J, Cao X, Vats P, Kunju LP, Hussain M, Feng FY, Tomlins SA, Cooney KA, Smith DC, Brennan C, Siddiqui J, Mehra R, Chen Y, Rathkopf DE, Morris MJ, Solomon SB, Durack JC, Reuter VE, Gopalan A, Gao J, Loda M, Lis RT, Bowden M, Balk SP, Gaviola G, Sougnez C, Gupta M, Yu EY, Mostaghel EA, Cheng HH, Mulcahy H, True LD, Plymate SR, Dvinge H, Ferraldeschi R, Flohr P, Miranda S, Zafeiriou Z, Tunariu N, Mateo J, Perez-Lopez R, Demichelis F, Robinson BD, Schiffman M, Nanus DM, Tagawa ST, Sigaras A, Eng KW, Elemento O, Sboner A, Heath EI, Scher HI, Pienta KJ, Kantoff P, de Bono JS, Rubin MA, Nelson PS, Garraway LA, Sawyers CL, Chinnaiyan AM. Integrative clinical genomics of advanced prostate cancer. Cell. 2015 May 21;161(5):1215-28. PMID: 26000489 / NIHMSID: 702018

Tomlins SA, Day JR, Lonigro RJ, Hovelson DH, Siddiqui J, Kunju LP, Dunn RL, Meyer S, Hodge P, Groskopf J, Wei JT, Chinnaiyan AM. Urine TMPRSS2:ERG Plus PCA3 for Individualized Prostate Cancer Risk Assessment. Eur Urol. 2015 May 15. pii: S0302-2838(15)00397-8. PMID: 25985884

Malik R, Khan AP, Asangani IA, Cieslik M, Prensner JR, Wang X, Iyer MK, Jiang X, Borkin D, Escara-Wilke J, Stender R, Wu YM, Niknafs YS, Jing X, Qiao Y, Palanisamy N, Kunju LP, Krishnamurthy PM, Yocum AK, Mellacheruvu D, Nesvizhskii AI, Cao X, Dhanasekaran SM, Feng FY, Grembecka J, Cierpicki T, Chinniayan AM. Targeting the MLL complex in castration-resistant prostate cancer. Nat Med. 2015 Apr;21(4):344-352. PMID: 25822367/ PMCID: PMC4390530

Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, Barrette TR, Prensner JR, Evans JR, Zhao S, Poliakov A, Cao X, Dhanasekaran SM, Wu YM, Robinson DR, Beer DG, Feng FY, Iyer HK, Chinnaiyan AM. The landscape of long noncoding RNAs in the human transcriptome. Nat Genet. 2015; 47(3):199-208. PMID: 25599403 / PMCID: PMC4417758

Dhanasekaran SM, Balbin OA, Chen G, Nadal E, Kalyana-Sundaram S, Pan J, Veeneman B,Cao X, Malik R, Vats P, Wang R, Huang S, Zhong J, Jing X, Iyer M, Wu Y-M, Harms PW, Lin J, Reddy R, Brennan C, Palanisamy N, Chang AC, Truini A, Truini M, Robinson DR, Beer DG, Chinnaiyan AM. Transcriptome Meta-Analysis of Lung Cancer Reveals Recurrent Aberrations in NRG1, NF1 and Hippo Pathway Genes. Nat Comm 2014 Dec 22;5:5893. PMID: 25531467/PMCID: PMC4274748

Feng FY, Brenner JC, Hussain M, Chinnaiyan AM. Molecular Pathways: Targeting ETS Gene Fusions in Cancer. Clin Cancer Res. 2014 Sep 1;20(17):4442-8. PMID: 24958807 / PMCID: PMC4155001

Malik R, Patel L, Prensner JR, Shi Y, Iyer M, Subramaniyan S, Carley A, Niknafs YS, Sahu A, Han S, Ma T, Liu M, Asangani IA, Jing X, Cao X, Dhaneshekaran SM, Robinson D, Feng FY, Chinnaiyan AM. The lncRNA PCAT29 Inhibits Oncogenic Phenotypes in Prostate Cancer. Mol Cancer Res. 2014 Aug;12(8):1081-7. doi: 10.1158/1541-7786.MCR-14-0257. PMCID: PMC4135019

Prensner JR, Chen W, Han S, Iyer MK, Cao Q, Kothari V, Evans JR, Knudsen KE, Paulsen MT, Ljungman M, Lawrence TS, Chinnaiyan AM, Feng FY. The Long Non-Coding RNA PCAT-1 Promotes Prostate Cancer Cell Proliferation through cMyc. Neoplasia. 2014 Nov 20;16(11):900-8. PMID: 25425964 / PMCID: PMC4240923 

Prensner JR, Zhao S, Erho N, Schipper M, Iyer MK, Dhanasekaran SM, Magi-Galluzzi C, Mehra R, Sahu A, Siddiqui J, Davicioni E, Den RB, Dicker AP, Karnes RJ, Wei JT, Klein EA, Jenkins RB, Chinnaiyan AM, Feng FY. RNA biomarkers associated with metastatic progression in prostate cancer: a multi-institutional high-throughput analysis of SChLAP1. Lancet Oncol. 2014 Dec;15(13):1469-80. PMID: 25456366 / NIHMSID: 644829

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