ANALISA DIFEO, PhDAssistant Professor
General Medical Sciences (Oncology)
The overall goal of Dr. DiFeo's laboratory is to identify novel biomarkers of ovarian cancer therapeutic response and generate novel targeted molecular therapies that can work alone or in conjunction with current treatment options to combat ovarian cancer. Specifically, the lab works on epithelial ovarian cancer (EOC), which is one of the most lethal female reproductive tract malignancies, and is usually diagnosed at advanced stage when disease has spread beyond the ovary. Approximately half the women diagnosed with ovarian cancer die from chemoresistant metastatic disease. Therefore, understanding the mechanisms of chemoresistance will aid in developing new treatment strategies and in identifying those patients that will respond to current strategies.
Dr. DiFeo's research program focuses on obtaining a better understanding of the mechanism by which small non-coding RNAs (microRNAs) are involved in ovarian tumor biology and the development and progression of ovarian cancer in cell culture and animal models. To date, effective methods to predict a patient's response to traditional or newer targeted therapies are lacking. Work in the laboratory is, therefore, focused on microRNAs that may serve as potential predictive markers for individualized therapy, and the development of novel therapeutic strategies. Using a combination of in vitro and in vivo approaches, we strive to better understand the mechanism by which both microRNA’s and the genes they regulate are involved in ovarian tumor biology and chemoresistance at the cellular level as well as disease development and progression in animals
Dr. DiFeo has received numerous awards including the Mary Kay Foundation Award, Liz Tilberis Ovarian Cancer Award, the American Association of Cancer Research AstraZeneca Scholar-in-Training Award, and the Doctoral Dissertation Award from Mount Sinai School of Medicine. In addition, she has also been awarded a grant from the Department of Defense on her work to identify and validate microRNA signatures that predict ovarian cancer patient response to chemotherapy.
Additionally, in order to ensure translation of basic laboratory discoveries into improved therapies and management of EOC, Dr. DiFeo has developed a Gynecologic Oncology Translational Research Working Group which consists of a multidisciplinary group of dedicated translational research scientists, gynecologic oncologists, clinical fellows, pathologists, computational biologists and biostatisticians focused on understanding the molecular defects associated with ovarian cancer initiation, progression and chemoresistance. Through this program they have developed an extensive gynecologic tumor biobank which includes a computer-integrated gynecologic cancer patient database and snap-frozen tumor tissue, patient serum, novel primary cancer cell lines, as well as patient-derived mouse xenografts.
Parikh A, Lee C, Joseph P, Marchini S, Baccarini A, Kolev V, Fruscio R, Shah H, Mullokandov, Fishman D, Romualdi C, D’Incalci M, Rahaman J, Kalir T, Redline RW, Brown BD, Narla G, and DiFeo A miR-181a induces TGF-β-mediated epithelial-to-mesenchymal transition and promotes epithelial ovarian cancer progression. Nature Communications, In Press.
Hatami R, Sieuwerts AM, Izadmehr S, Yao Z, Qiao RF, Papa L, Look MP, Smid M, Ohlssen J, Levine AC, Germain D, Burstein D, Kirschenbaum A, DiFeo A, Foekens JA, Narla G. KLF6-SV1 drives breast cancer metastasis and is associated with poor survival. Sci Transl Med. 20135:169.
Sangodkar J, Dhawan NS, Melville H, Singh VJ, Yuan E, Rana H, Izadmehr S, Farrington C, Mazhar S, Katz S, Albano T, Arnovitz P, Okrent R, Ohlmeyer M, Galsky M, Burstein D, Zhang D, Politi K, Difeo A, Narla G Targeting the FOXO1/KLF6 axis regulates EGFR signaling and treatment response. J Clin Invest. 2012;122(7):2637-51.
Calderon MR, Verway M, An BS, DiFeo A, Bismar TA, Ann DK, Martignetti JA, Shalom-Barak T, White JH. Ligand-dependent Corepressor (LCoR) Recruitment by Kruppel-like Factor 6 (KLF6) Regulates Expression of the Cyclin-dependent Kinase Inhibitor CDKN1A Gene. J Biol Chem. 287(12):8662-74; 2012.
Rodríguez E, Aburjania N, Priedigkeit NM, DiFeo A, Martignetti JA. Nucleo-cytoplasmic localization domains regulate Krüppel-like factor 6 (KLF6) protein stability and tumor suppressor function. PLoS One. 9;5(9);2010.
DiFeo A, Narla G, Huang F, Terzo EA, Leake D and Martignetti JA. KLF6-SV1 is a novel antiapoptotic protein that targets the BH3-only protein NOXA for degradation and whose inhibition extends survival in an ovarian cancer model. Cancer Research 69(11):4733-41; 2009.
Sanborn KB, Rak GD, Maru SY, Demers K, DiFeo A, Martignetti JA, Betts MR, Favier R, Banerjee PP, Orange JS. Myosin IIA associates with NK cell lytic granules to enable their interaction with F-actin and function at the immunological synapse. J Immunol. 182(11):6969-84; 2009.
Sangodkar J, DiFeo A, Feld L, Bromberg R, Schwartz R, Huang F, Terzo EA, Choudhri A, Narla G.Targeted reduction of KLF6-SV1 restores chemotherapy sensitivity in resistant lung adenocarcinoma. Lung Cancer. 66(3):292-7; 2009.
DiFeo A, Martignetti JA, Narla G. The role of KLF6 and its splice variants in cancer therapy. Drug Resist Updat. 12(1-2):1-7; 2009.
DiFeo A*, Narla G*, Fernandez Y, Dhanasekaran S, Huang F, Sangodkar J, Hod E, Leake D, Friedman SL, Hall S, Chinnaiyan AM, Gerald WL, Rubin MA, and Martignetti JA. KLF6-SV1 overexpression accelerates prostate cancer progression and metastasis. J Clin Invest. 118( 8) :2711-21; 2008
DiFeo A, Feld L, Estefania Rodriquez, Christine Wang, Beer DG, Martignetti JA, and Narla G. A functional role for KLF6-SV1 in lung cancer development and chemotherapy response. Cancer Research 68 (4):1-6; 2008
DiFeo A, Narla G, Hirshfeld J, Camacho-Vanegas O, Narla J, Rose SL, Kalir T, Yao S, Levine A, Friedman S.L, Buller RE and Martignetti JA. Roles of KLF6 and KLF6-SV1 in ovarian cancer progression and intraperitoneal dissemination. Clinical Cancer Res. 12(12):3730-9; 2006.
DiFeo A, Narla G, Camacho-Vanegas O, Nishio H, Rose SL, Buller RE, Friedman SL, Walsh MJ and Martignetti JA. E-cadherin is a novel transcriptional target of the KLF6 tumor suppressor. Oncogene. 25(44):6026-31; 2006.
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 B, Chinnaiyan AM, Rubin MA, Xu J, Thibodeau SN, Friedman SL, Martignetti JA. A germline DNA polymorphism associated with increased prostate cancer risk enhances alternative splicing of the KLF6 tumor suppressor gene. Cancer Res 65(4):1213-22; 2005.
Narla G, DiFeo A, Yao S, Banno A, Hod E, Reeves HL, Qiao RF, Camacho-Vanegas O, Levine A, Kirschenbaum A, Chan AM, Friedman SL, Martignetti JA. Targeted inhibition of the KLF6 splice variant, KLF6 SV1, suppresses prostate cancer cell growth and spread. Cancer Res. 65(13):5761-8; 2005.