- Ovarian Cancer
- Tumor Biology
- Epithelial-To-Mesenchymal Transition
- Patient-Derived Xenografts
Dr. DiFeo has received numerous awards including the Mary Kay Foundation Award, Liz Tilberis Early Career 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.
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.
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.
Dimitrova N, Mittal, Belur Nagaraj A, Razi A, Kamalakaran, Banerjee, Singh, Mankovich, DiFeo A*, Varadan V* InFlo: A Novel Systems Biology Framework Identifies cAMP-CREB1 Axis as a Key Modulatory of Platinum Resistance in Ovarian Cancer. Oncogene. 2017 Apr 27;36(17):2472-2482.
Wiechert A, Saygin C, Thiagarajan PS, Rao V, Hale JS, Gupta N, Hitomi M, Nagaraj AB, DiFeo A, Lathia JD, Reizes O. Cisplatin induces stemness in ovarian cancer. Oncotarget. 2016;7(21):30511-22. doi: 10.18632/oncotarget.8852.
Hudson CD, Saadelis A, Belur Nagaraj A, Joseph P, Avril S, DiFeo A*, Avril N*. Altered Glutamine Metabolism in Platinum Resistant Ovarian Cancer. Oncotarget. 2016 doi: 10.18632/oncotarget.9317.
Nagaraj A, Joseph PL, Kovalenko O, Singh S, Resnick K, Zanotti K, Waggoner S, DiFeo A. Critical role of Wnt/β-catenin signaling in driving epithelial ovarian cancer platinum resistance. Oncotarget. 2015 Sep 15;6(27):23720-34.
Nagari A, Joseph PL, DiFeo A. miRNAs as Prognostic and Therapeutic Tools in Epithelial Ovarian Cancer. Biomark Med. 2015 Mar;9(3):241-57.
Carter RR, Difeo A, Bogie K, Zhang GQ, Sun J. Crowdsourcing awareness: Exploration of the ovarian cancer knowledge gap through Amazon Mechanical Turk. PLoS One. 2014 Jan 22;9(1):e85508. PMCID: PMC3899016
Parikh A, Lee C, Joseph P, Marchini S, Baccarini A, Kolev V, Romualdi C, Fruscio R, Shah H, Wang F, Mullokandov G, Fishman D, D'Incalci M, Rahaman J, Kalir T, Redline RW, Brown BD, Narla G, Difeo A. microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition. Nat Commun. 2014 Jan 7;5:2977. PMCID: PMC3896774
Favier R, DiFeo A, Hezard N, Fabre M, Bedossa P, Martignetti JA. A new feature of the MYH9-related syndrome: chronic transaminase elevation. Hepatology. 2013 Mar;57(3):1288-9.
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. 2013 Jan 23;5(169):169ra12.
Mosoyan G, Nagi C, Marukian S, Teixeira A, Simonian A, Resnick-Silverman L, Difeo A, Johnston D, Reynolds SR, Roses DF, Mosoian A. Multiple breast cancer cell-lines derived from a single tumor differ in their molecular characteristics and tumorigenic potential. PLoS One. 2013;8(1):e55145. PMCID: PMC3555897
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.