Assistant Professor of Pathology
Scott Tomlins, M.D., Ph.D., is an Assistant Professor in the Department of Pathology and MCTP.
My research has focused on using high-throughput techniques to characterize the cancer genome and transcriptome to identify cancer-specific aberrations to better understand cancer biology and identify clinically relevant biomarkers and therapeutic targets. My most important contribution has been discovering TMPRSS2:ETS gene fusions in prostate cancer, which play a fundamental role in prostate cancer development and have potential as biomarkers for early detection, risk stratification and therapeutic targeting. I have led studies characterizing the diversity of gene fusions, their in vitro function, and generation and characterization of transgenic mouse models. This finding is the basis for ongoing efforts to molecularly subclassify prostate cancer, which also incorporates additional gene fusions we identified as well as a subtype over-expressing SPINK1, which encodes a protease that may be targeted therapeutically. Research in my newly established laboratory utilizes integrative high-throughput approaches to molecularly profile genitourinary malignancies, including clinical subtyping of prostate cancer, as well as bladder and adrenocortical carcinoma.
Important to the success of this proposal, I led initial validation studies using cDNA microarray and qPCR analysis of the TransPlex Whole Transcriptome Amplification technology from Rubicon Genomics that will be utilized in this proposal. Similarly, I co-led the initial application of this technology to urine sediments to detect TMRPPSS2:ERG gene fusions by qPCR, either alone or in multiplex. I have also led follow-up studies using clinical grade assays developed by Gen-Probe for TMPRSS2:ERG and the lncRNA PCA3, including comparisons to prostatectomy tissue expression of ERG. As a member of the University of Michigan Center for Translational Pathology and Prostate Cancer S.P.O.R.E., I have full access to banked urine samples and matched prostatectomy samples that can be assessed for lncRNA and Gleason grade associated transcripts by TransPlex and qPCR.
2000: Barry M. Goldwater Scholar
2001: Phi Beta Kappa, Willamette University
2006: American Society for Investigative Pathology, Experimental Pathologist in Training Award
2006: American Society for Clinical Investigation and Association of American Physicians, Stanley J. Korsmeyer Young Investigator Award
2006: Rackham Predoctoral Fellowship, University of Michigan
2007: American Cancer Society Travel Scholarship, Active Surveillance for Early Stage Prostate Cancer
2007: Harold M. Weintraub Graduate Student Award, Fred Hutchinson Cancer Research Center
2007: American Association for Cancer Research Team Science Award
2007: Prostate Cancer Foundation, Young Investigator Award
2008: Horace H. Rackham Distinguished Dissertation Award, University of Michigan
2008: Blue Cross Blue Shield of Michigan Foundation, First Place Excellence in Research Award for Students
2009: Selected for Future Leaders Special Symposium, AACR 100th Annual Meeting
2009: George R. Demuth Award, University of Michigan MSTP
2011: Excellence in Urologic Pathology Award, International Society of Urological Pathology
2011: AACR-Prostate Cancer Foundation Scholar-in-Training Award, AACR 102nd Annual Meeting 2011
2012: Selected as Biological Sciences Scholars Program scholar, University of Michigan
Selected Peer-Reviewed Publications (15 from a total of 66 peer-reviewed publications):
- Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005 Oct 28;310(5748):644-8. PMID: 16254181.
- Tomlins SA, Mehra R, Rhodes DR, Smith LR, Roulston D, Helgeson BE, Cao X, Wei JT, Rubin MA, Shah RB, Chinnaiyan AM. TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res. 2006 Apr 1;66(7):3396-400. PMID: 16585160.
- Laxman B*, Tomlins SA*, Mehra R, Morris DS, Wang L, Helgeson BE, Shah RB, Rubin MA, Wei JT, Chinnaiyan AM. Noninvasive Detection of TMPRSS2:ERG Fusion Transcripts in the Urine of Men with Prostate Cancer. Neoplasia. 2006 Oct;8(10):885-8. (* = equal authorship).
- Tomlins SA, Mehra R, Rhodes DR, Cao X, Wang L, Dhanasekaran SM, Kalyana-Sundaram S, Wei JT, Rubin MA, Pienta KJ, Shah RB, Chinnaiyan AM. Integrative molecular concept modeling of prostate cancer progression. Nat Genet. 2007 Jan;39(1):41-51. Epub 2006 Dec 17. PMID: 17173048.
- Tomlins SA, Laxman B, Dhanasekaran SM, Helgeson BE, Cao X, Morris DS, Menon A, Jing X, Cao Q, Han B, Yu J, Wang L, Montie JE, Rubin MA, Pienta KJ, Roulston D, Shah RB, Varambally S, Mehra R, Chinnaiyan AM. Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature. 2007 Aug 2;448(7153):595-9. PMID: 17671502.
- Helgeson BE*, Tomlins SA*, Shah N*, Laxman B, Cao Q, Prensner JR, Cao X, Singla N, Montie JE, Varambally S, Mehra R, Chinnaiyan AM. Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer. Cancer Res. 2008 Jan 1;68(1):73-80. PMID: 18172298.
- Laxman B*, Morris DS*, Yu J*, Siddiqui J, Cao J, Mehra R, Lonigro RJ, Tsodikov A, Wei JT, Tomlins SA*, Chinnaiyan AM. A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer. Cancer Res. 2008 Feb 1;68(3):645-9. PMID:18245462. PMCID:PMC2998181.
- Tomlins SA, Rhodes DR, Yu J, Varambally S, Mehra R, Perner S, Demichelis F, Helgeson BE, Laxman B, Morris DS, Cao Q, Cao X, Andren O, Fall K, Johnson L, Wei JT, Shah RB, Al-Ahmadie H, Eastham JA, Eggener SE, Fine SW, Hotakainen K, Stenman UH, Tsodikov A, Gerald WL, Lilja H, Reuter VE, Kantoff PW, Scardino PT, Rubin MA, Bjartell AS, Chinnaiyan AM. The role of SPINK1 in ETS rearrangement-negative prostate cancers. Cancer Cell. 2008 Jun;13(6):519-28. PMID: 18538735; PMCID: PMC2732022.
- Tomlins SA, Mehra R, Rhodes, DR, Shah RB, Rubin MA, Bruening E, Makarov
V, Chinnaiyan AM. Whole Transcriptome Amplification for Gene Expression
Profiling and Development of Molecular Archives. Neoplasia. 2006
- Mani RS, Tomlins SA, Callahan K, Ghosh A, Nyati MK, Varambally S,
Palanisamy N, Chinnaiyan AM. Induced chromosomal proximity and gene
fusions in prostate cancer. Science. 2009 Nov 27;326(5957):1230. Epub
2009 Oct 29. PMID: 19933109. PMCID:PMC29355.
- Park K*, Tomlins SA*, Mudaliar KM, Chiu YL, Esgueva R, Mehra R, Suleman
K, Varambally S, Brenner JC, Macdonald T, Srivastava A, Tewari AK,
Sathyanarayana U, Nagy D, Pestano G, Kunju LP, Demichelis F, Chinnaiyan
AM, Rubin MA. Antibody-Based Detection of ERG Rearrangement-Positive
Prostate Cancer. Neoplasia. 2010 Jul;12(7):590-8. PMID: 20651988. PMCID:PMC2907585.
- Ateeq B, Tomlins SA, Laxman B, Asangani IA, Cao Q, Cao X, Li Y, Wang X, Feng FY, Pienta KJ, Varambally S, Chinnaiyan AM. Therapeutic targeting of SPINK1-positive prostate cancer. Sci Transl Med. 2011 Mar 2;3(72):72ra17. PMID:21368222. PMCID:PMC3211047.
- Tomlins SA, Aubin SM, Siddiqui J, Lonigro RJ, Sefton-Miller L, Miick S, Williamsen S, Hodge P, Meinke J, Blase A, Penabella Y, Day JR, Varambally R, Han B, Wood D, Wang L, Sanda MG, Rubin MA, Rhodes DR, Hollenbeck B, Sakamoto K, Silberstein JL, Fradet Y, Amberson JB, Meyers S, Palanisamy N, Rittenhouse H, Wei JT, Groskopf J, Chinnaiyan AM. Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Sci Transl Med. 2011 Aug 3;3(94):94ra72. PMCID: PMC3245713.
- Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP, Quist MJ, Jing X, Lonigro RJ, Brenner JC, Asangani IA, Ateeq B, Chun SY, Siddiqui J, Sam L, Anstett M, Mehra R, Prensner JR, Palanisamy N, Ryslik GA, Vandin F, Raphael BJ, Kunju LP, Rhodes DR, Pienta KJ, Chinnaiyan AM, Tomlins SA. The mutational landscape of lethal castration-resistant prostate cancer. Nature. 2012 May 20. doi: 10.1038/nature11125. PMCID: PMC3396711.
- Young A, Palanisamy N, Siddiqui J, Wood DP, Wei JT, Chinnaiyan AM, Kunju LP, Tomlins SA. Correlation of Urine TMPRSS2:ERG and PCA3 to ERG+ and Total Prostate Cancer Burden. Am J Clin Pathol. 2012 Nov;138(5):685-96. doi: 10.1309/AJCPU7PPWUPYG8OH. NIHMSID # 437386.