Clinical Interests: Medical Genetics, Cancer Genetic Counseling, Hereditary Cancer Syndromes, Genetic Testing
Since first discovering the KLF6 gene as a Mount Sinai medical student, Goutham Narla, MD, PhD continues to lay the groundwork for improving diagnosis and treatment of metastatic cancers. Find out more in Inside Mount Sinai.
Dr. Narla has been involved in the identification and characterization of the KLF6 gene and its role in cancer development and progression. Dr. Narla was the first to identify that KLF6 was a tumor suppressor gene in cancer with his mentor Dr. Scott Friedman. He then went on to identify and characterize the oncogenic splice variant KLF6-SV1 in several different malignancies. His work on the molecular alterations underlying the development and progression of cancer could lay the groundwork for the better diagnosis and treatment of this deadly disease.
Dr. Narla is a recent graduate of the MSTP program at the Mount Sinai School of Medicine. He completed his PhD training with Dr. Scott Friedman, Chief of Liver Diseases. Goutham is now an Assistant Professor in the Departments of Genetics and Genomic Sciences and Medicine at the Mount Sinai Hospital. He is also Director of Physician Scientist Training for the Residency Program and Director of Medical Student Professional Development and Residency Planning.
Dr. Narla's laboratory focuses on the identification and characterization of the genes and pathways involved in cancer metastasis. By testing the functional role of the KLF6 tumor suppressor gene and its oncogenic splice variant KLF6-SV1, Dr. Narla has identified new signaling pathways regulated by this gene family and provided new insight into cancer diagnosis, prognosis and treatment.
Dr. Narla has won numerous awards including the Harold Lamport Biomedical Research Prize, a Howard Hughes Medical Student Research Fellowship, and the Graduate Research Achievement Award. He was recently award a grant from the Howard Hughes Medical Institute to continue his work on the molecular mechanisms underlying prostate cancer metastasis.
PhD, The Mount Sinai School of Medicine
Physician Scientist Early Career Award
Humanism and Excellence in Teaching Arnold P. Gold Foundation
AASLD Resident Scholar Travel Award
Graduate School Travel Award
Graduate Research Achievement Award
Biovision International Biotechnology Conference Travel Award
American Society of Human Genetics Medical Student Travel Award
Howard Hughes Medical Student Research Fellowship
American Liver Foundation Student Research Grant
NIH/AMSA Research Prize
Specific Clinical/Research Interests: Role of tumor suppressor and oncogenes in tumorigenesis and metastasis; genetics of chemotherapy resistance
Current Students: Raheleh Hatami, Jaya Sangodkar
Postdoctoral Fellows: Arpita Ray
Research Personnel: Rachel Schwartz, Pearl Arnovitz, Alison Carley, Kim McClinch, Jiayan Shi, Romina Bromberg
Role of the KLF6 gene family in human cancer: We have identified the KLF6 gene as a tumor suppressor gene inactivated in human cancer through a number of functional mechanisms including loss of heterozygosity (LOH), somatic mutation, promoter hypermethylation, and alternative splicing into an oncogenic splice variant KLF6-SV1. Major projects currently ongoing in my laboratory are:
1. Understanding the molecular mechanisms and pathways regulated by KLF6 and KLF6-SV1 in breast and lung cancer
2. Expression pattern of the KLF6 gene family as a potential prognostic marker in several major malignancies
3. The role of the KLF6 gene family in EGF-R and AKT signaling
4. Mouse models of the KLF6 gene family to further define its role in cancer development and progression
5. Analyzing the expression of KLF6 and KLF6-SV1 in human cancer
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. European Journal of Cancer;: in press.
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. Journal of Clinical Investigation 2008; 118: 2711-2721.
DiFeo A, Feld L, Rodriguez E, Wang C, Beer DG, Martignetti JA, Narla G. A functional role for KLF6-SV1 in lung adenocarcinoma prognosis and chemotherapy response. Cancer Research 2008; 68: 965-970.
Yea S, Narla G, Zhao X, Garg R, Tal-Kremer S, Hod E, Villaneuva A, Loke J, Tarocchi M, Akita K, Shirasawa S, Sasasuki T, Martignetti JA, Llovet JM, Friedman SL. Ras promotes growth by alternative splicing-mediated inactivation of the KLF6 tumor suppressor gene in hepatocellular carcinoma. Gastroenterology 2008; 20: 1521-1531.
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: 4428-4434.
DiFeo A, Narla G, Hirschfeld J, Camacho-Vanegas O, Yao S, Rose S, Kalir T, Friedman SL, Buller RE, Martignetti JA. Role of KLF6 and KLF6-SV1 in ovarian cancer progression and intraperitoneal dissemination. Clin Cancer Res 2006; 12: 3730-3739.
DiFeo A, Narla G, Camacho-Vanegas O, Nishio H, Rose S, Buller RE, Friedman SL, Walsh MJ, Martignetti JA. E-cadherin is a novel transcriptional target of the KLF6 tumor suppressor. Oncogene 2006; 25: 26-31.
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 Research 2005; 65: 1213-1222.
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 Research 2005; 65: 5761-5768.
Reeves HL, Narla G, Ogunbiyi O, Haq A, Katz A, Benzeno S, Hod E, Harpaz N, Goldberg S, Tal-Kremer S, Eng FJ, Arthur MJ, Martignetti JA, Friedman SL. Kruppel-like factor 6 (KLF6) is a tumor suppressor gene frequently inactivated in colorectal cancer. Gastroenterology 2004; 126: 1090-1103.