Administrative Assistant: Linda J. Howell
Division of Genetic Medicine
University of Michigan Medical School
Phone: (734) 763-5798, Fax: (734) 647-9647
Dr. Goutham Narla earned his BS in Biology and Economics from Santa Clara University in California and his MD and PhD from Mount Sinai School of Medicine in New York. He also completed his residency in Internal Medicine and fellowship in Medical Genetics at Mount Sinai. After finishing his fellowship, he moved to Ohio in 2012 to work at Case Western Reserve University (CWRU), where he later become an Associate Professor with tenure. In July 2018, he joined the faculty at Michigan Medicine to become the seventh Chief of the Division of Genetic Medicine since the division’s inception in 1977.
Dr. Narla has held several leadership positions, particularly focusing on education and training, both at Mount Sinai and CWRU. At Mount Sinai, he served as the Director of the Physician-Scientist Training Residency Program, Assistant Program Director of the Medical Scientist Training Program (MSTP), and was a member of the Medical School Admissions Committee. At CWRU, Dr. Narla sat on the MSTP Steering Committee and the Pharmacology Steering Committee. In 2012, he was named the first Harrington Distinguished Scholar (Early Career Award). He is currently the President of The Young Scientist Foundation, and a member of the American Association for Cancer Research and the American Society for Clinical Investigation.
While in medical school, Dr. Narla trained in Dr. Scott Friedman’s laboratory at Mount Sinai, where he first discovered the KLF6 gene and its ability to suppress cancerous tumors. His current research focuses on the identification and characterization of the key negative regulators, tumor suppressor proteins, of cancer development and progression, and the development of small molecule-based therapies that activate tumor suppressor genes for the treatment of cancer. To date, Dr. Narla has authored 11 patents. He has over 65 publications in journals including Nature Genetics, Science, Science Translational Medicine, Proceedings of the National Academy of Sciences, and the Journal of Clinical Investigation.
Areas of Interest
My research interests focus on understanding the mechanisms driving human cancer development and progression and has led to: 1) the identification of a new class of tumor suppressor genes in human cancer (the Kruppel-like factor family of genes), 2) the characterization of novel mechanisms of tumor suppressor gene inactivation in cancer progression (alternative splicing into dominant negative oncogenic splice variants), 3) the development and validation of pharmaceutically tractable strategies to reactive tumor suppressor gene function for the treatment of a broad range of human cancers, and 4) the structural, functional and biological mechanisms of PP2A inactivation in human cancer. These studies span the continuum of biomedical research starting from fundamental mechanism-driven laboratory-based studies directed at identifying novel cancer genes to the translation of these findings into the development of new drugs for cancer treatment. These novel small-molecule tumor suppressor gene activators represent the first, to our knowledge, example of drugs that directly bind and activate tumor suppressor genes for cancer treatment and provide the mechanistic and translational framework/foundation to develop entire classes of drugs directed at the key negative regulators of oncogenic signaling, an area that to date has not been the focus of major drug development efforts.
I am a physician scientist and trained as a medical geneticist in the care of high risk cancer and medical genetics patients. I completed residency training in internal medicine and fellowship training in Medical Genetics at the Mount Sinai Hospital in New York. Clinically, I lead the Division of Genetic Medicine that cares for over 3000 high-risk cancer and medical genetics patients per year. I oversee 30 faculty and staff members who are involved both in the research of the genetic basis of human disease as well as in the care at a system wide level for genetics patients at Michigan Medicine.
Honors & Awards
2000 Harold Lamport Biomedical Research Prize, Mount Sinai School of Medicine
2000 Research Prize, NIH/AMSA
2000 Student Research Grant, American Liver Foundation
2001 Medical Student Research Fellowship, Howard Hughes Medical Institute
2004 Biotechnology Conference Travel Award, Biovision International
2005 Graduate Research Achievement Award, Mount Sinai School of Medicine
2008 Humanism and Excellence in Teaching, Arnold P. Gold Foundation
2010 Saul Horowitz, Jr. Memorial Award
2012 James T. Pardee - Carl A. Gerstacker Professorship in Cancer Research
2012 Harrington Distinguished Scholar (Early Career Award)
2013 Crain’s Health Care Hero – Advancements in Healthcare
2015 John S. Diekhoff Graduate Mentorship Award
2016 American Society of Clinical Investigation (ASCI)
2018 Elias Tillandr Prize, Best Publication 2018, “PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS mutant lung cancer cells. Sci Transl Med”
1997; BS, Biology & Economics, Santa Clara University, Santa Clara, CA
2006; MD, PhD, Cancer Biology/Genetics, Mount Sinai School of Medicine, New York, NY
- Narla G, Heath KE, Reeves HL, Li D, Giono LE, Kimmelman AC, Glucksman MJ, Narla J, Eng FJ, Chan AM, Ferrari AC, Martignetti JA, Friedman SL. KLF6, a candidate tumor suppressor gene in prostate cancer. Science 2001;21:2563-6. PMID: 11752579
- Benzeno S, Narla G, Allina J, Cheng GZ, Reeves HL, Banck MS, Odin JA, Diehl JA, Germain D, Friedman SL. Cyclin-dependent kinase inhibition by the KLF6 tumor suppressor protein through interaction with cyclin D1. Cancer Res 2004;64: 3885-91. PMID: 15172998
- Narla G, Kremer-Tal S, Matsumoto N, Zhao X, Yao S, Kelley K, Tarocchi M, Friedman SL. In vivo Regulation of p21 by the KLF6 Tumor Suppressor Gene in Mouse Liver and Human Hepatocellular Carcinoma. Oncogene 2007;26:4428-34. PMID: 17297474
- Sangodkar J, Shi J, DiFeo A, Schwartz R, Bromberg R, Choudhri A, McClinch K, Scheer E, Martignetti J, Hui A, Leung WK, Friedman SL, Narla G. Functional role of the KLF6 tumor suppressor gene in gastric cancer. Eur J Cancer 2009;45:666-76. PMID: 19101139
- Narla G, DiFeo A, Reeves HL, Schaid DJ, Hirshfeld J, Hod E, Katz A, Isaacs WB, Hebbring S, Komiya A, McDonnell SK, Wiley KE, Jacobsen SJ, Isaacs SD, Walsh PC, Zheng SL, Chang BL, Friedrichsen DM, Stanford JL, Ostrander EA, Chinnaiyan AM, Rubin MA, Xu J, Thibodeau SN, Friedman SL, Martignetti JA. A germline DNA polymorphism enhances alternative splicing of the KLF6 tumor suppressor gene and is associated with increased prostate cancer risk. Cancer Res 2005;65:1213-22. PMID: 15735005
- Narla G, DiFeo A, Yao S, Banno A, Hod E, Reeves H, Qiao RF, Camacho-Vanegas O, Levine A, Kirschenbaum A, Chan AM, Friedman SL, Martignetti JA. Targeted inhibition of the KLF6 splice variant KLF6SV1 suppresses prostate cancer growth and spread. Cancer Res 2005;65:5761-8. PMID: 15994951
- Narla G, DiFeo A, Fernandez Y, Dhanasekaran S, Huang F, Sangodkar J, Hod E, Leake D, Friedman SL, Hall S, Chinnaiyan AM, Gerald WL, Rubin MA, Martignetti JA. KLF6-SV1 is a key regulator of metastasis and survival in prostate cancer. J Clin Invest 2008;118:2711-2721. PMCID: 18596922
- Hatami R, Sieuwerts AM, Izadmehr S, Yao Z, Qiao R, Papa L, Look MP, Smid M, Ohlssen J, Levine AC, Germain D, Burstein D, Kirschenbaum A, DiFeo A, Foekens JA, and Narla G. An oncogenic splice variant of the KLF6 gene is associated with poor survival and a potent driver of breast cancer metastasis. Sci Transl Med 5 ,169ra12 (2013). PMID: 23345610
- Stachnik A, Yuen T, Iqbal J, Sgobba M, Gupta Y, Lu P, Colaianni G, Ji Y, Zhu L, Kim SM, Li J, Liu P, Izadmehr S, Sangodkar J, Scherer T, Mujtaba S, Galsky M, Gomez J, Epstein S, Buettner C, Bian Z, Zallone A, Aggarwal A, Haider S, New M, Sun L, Narla G*, Zaidi M*. (*co-senior authors). Repurposing of bisphosphonates for the prevention and therapy of non-small cell lung and breast cancer. Proc Natl Acad Sci; 16: 17955-8000; 2014. PMID: 25453078
- Yuen T, Stachnik A, Iqbal J, Sgobba M, Gupta Y, Lu P, Colaianni G, Ji Y, Zhu L, Kim SM, Li J, Liu P, Izadmehr S, Sangodkar J, Bailey J, Latif L, Mujtaba S, Epstein S, Davies T, Bian Z, Zallone A, Aggarwal A, Haider S, New M, Sun L, Narla G*, Zaidi M*. (*co-senior authors) Bisphosphonates inactivate human EGFRs to exert anti-tumor actions. Proc Natl Acad Sci; 16: 17989-94, 2014. PMID: 25453081
- Sangodkar J, Dhawan N, Melville H, Singh V, Katz S, Albano T, Farrington C, Rana H, Yuan E, Arnovitz P, Galsky M, Olhmeyer M, Burstein D, Zhang D, Politi K, Difeo A, and Narla G. The FOXO1/KLF6 transcriptional network negatively regulates activated EGFR signaling and modulates response to anti-EGFR based therapy. J Clin Invest 2012;122:2637-51. PMID: 22653055
- Sangodkar J, Perl A, Tohme R, Kiselar J, Kastrinsky DB, Zaware N, Izadmehr S, Mazhar S, Wiredja DD, O'Connor CM, Hoon D, Dhawan NS, Schlatzer D, Yao S, Leonard D, Borczuk AC, Gokulrangan G, Wang L, Svenson E, Farrington CC, Yuan E, Avelar RA, Stachnik A, Smith B, Gidwani V, Giannini HM, McQuaid D, McClinch K, Wang Z, Levine AC, Sears RC, Chen EY, Duan Q, Datt M, Haider S, Ma'ayan A, DiFeo A, Sharma N, Galsky MD, Brautigan DL, Ioannou YA, Xu W, Chance MR, Ohlmeyer M, Narla G. Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth. J Clin Invest. 2017 Jun 1;127(6):2081-2090. PMID: 28504649
- McClinch K, A Avelar R, Callejas D, Izadmehr S, Wiredja D, Perl A, Sangodkar J, Kastrinsky DB, Schlatzer D, Cooper M, Kiselar J, Stachnik A, Yao S, Hoon D, McQuaid D, Zaware N, Gong Y, Brautigan DL, Plymate S, Sprenger CC, Oh WK, Levine AC, Kirschenbaum A, Sfakianos JP, Sears RC, DiFeo A, Ioannou YA, Ohlmeyer M, Narla G*, Galsky MD* (*co-senior authors). Small molecule activators of protein phosphatase 2A for the treatment of castration-resistant prostate cancer. Cancer Res. 2018 Apr;78(8):2065-80. PMID: 29358171
- Tohme R, Izadmehr S, Gandhe S, Tabaro G, Vallabhaneni S, Thomas A, Vasireddi N, Dhawan NS, Ma’ayan A, Sharma N, Galsky MD, Ohlmeyer M, Sangodkar J, Narla G. Direct activation of PP2A for the treatment of tyrosine kinase inhibitor resistant lung adenocarcinoma. JCI Insight. 2019 Feb 21;4(4). PMID: 30830869.
- Leonard D, Huang W, Izadmehr S, O’Connor CM, Wiredja D, Wang Z, Zaware N, Chen Y, Schlatzer D, Kiselar J, Vasireddi N, Schuechner S, Perl A, Galsky M, Xu W, Brautigan DL, Ogris E, Taylor D, and Narla G. Selective PP2A enhancement through biased heterotrimer stabilization. Cell. 2020 Apr 30;181(3):688-701. PMID: 32315618
- Farrington C, Yuan E, Mazhar S, Izadmehr S, Hurst L, Allen-Petersen B, Janghorban M, Chung E, Wolczanski G, Galsky M, Sears R, Sangodkar J, Narla G. Protein phosphatase 2A activation as a therapeutic strategy for managing MYC-driven cancers. J Biol Chem. 2020 Jan 17;295(3):757-70. PMID: 31822503
- Kauko O, O’Connor CM, Kulesskiy E, Sangodkar J, Aakula A, Izadhmehr S, Yetukuri L, Yadav B, Padzik A, Laajala TD, Haapaniemi P, Momeny M, Varila T, Ohlmeyer M, Aittokallio T, Wennerberg K, Narla G*, Westermarck J* (*co-senior authors). PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS mutant lung cancer cells. Sci Transl Med. 2018 Jul 18;10(450). PMID: 30021885
- O’Connor CM, Hoffa, MT, Taylor SE, Avelar RA, Narla G. Protein Phosphatase 2A Aa regulates Ab protein expression and stability. J.Biol.Chem 2019 294(15):5923-34. PMID: 30796164.
- Taylor SE, DiFeo A, O’Connor CM, Wang Z, Shen G, Song H, Leonard D, Sangodkar J, LaVasseur C, Avril S, Waggoner S, Zanotti K, Armstrong AJ, Nagel C, Resnick K, Singh S, Jackson MW, Xu W, Haider S, Narla G. The highly recurrent PP2A Aα-subunit mutation P179R alters protein structure and impairs PP2A enzyme function to promote endometrial tumorigenesis. Cancer Res. 2019 May. PMID: 31142515
- Mazhar S, Leonard D, Sosa A, Schlatzer D, Thomas D, Narla G. Challenges and reinterpretation of antibody-based research on phosphorylation of Tyr307 on PP2Ac. Cell Reports. 2020 Mar 3;30(9):3164-3170. PMID: 32130915