Erin George, MD

The overarching goal of the George lab is to identify novel targets and strategies to overcome drug resistance in gynecologic cancers, with a particular focus on ovarian cancer. Dr. George is expanding a preclinical drug development platform, which includes both 2D and 3D tissue culture systems as well as orthotopic patient-derived xenograft (PDX) models developed from patients’ tumors collected at the time of their surgery. Tissue cultures can be used for drug screens and mechanism studies and PDXs can be expanded for preclinical trials validating the efficacy of treatment strategies identified at the bench. All cultures and PDX models are characterized genomically and proteomically, which will help strategize which genes or protein pathways to target. PDX tumors are again characterized before and after drug treatment to identify biomarkers of response and resistance to guide future clinical trial design and identify future areas of study. The ultimate goal of the lab is to bring therapies with strong preclinical evidence to patients via phase I/II clinical trials.

Associations

• Drug Discovery
• Gynecologic Oncology
• BioEngineering
• Molecular Medicine Program

Education & Training

Fellowship:

• Hospital of the University of Pennsylvania - Gynecologic Oncology

Residency:

• New York Presbyterian Hospital – Columbia University - Obstetrics and Gynecology

Medical School:

• Columbia University College of Physicians and Surgeons - MD

My goal is to bring novel targeted therapies and combination treatment strategies to gynecologic oncology patients via phase I/II clinical trials. In order to achieve those goals, I have established a translational lab that utilizes the capabilities of patient-derived model systems. My active tissue collection protocol allows for the collection of patient tumor and/or ascites at the time of surgery, biopsies, and / or paracentesis. These patient samples are used to generate orthotopic ovarian cancer patient derived xenograft models (PDXs) as well as microtumor explants in a novel perfusion system (in collaboration with Drs. Greg Sawyer and Elsa Flores). I also work closely with my primary research mentor, Dr. Uwe Rix, in Drug Discovery, in order to identify novel targeted combination treatment options for different molecular subsets of ovarian cancer using compounds that are clinically available in order to facilitate rapid translation to the clinic. Potential targeted combinations are validated, and mechanisms interrogated in available established cell lines and primary patient-derived 2D and 3D cultures. The microtumor explants and orthotopic PDX models are used to confirm in vitro findings. Based on our preclinical studies, my goal is to propose an investigator-initiated trial, which will utilize the microtumor explant culture system as a Bioengineering tool to help improve translational endpoints.

• Gitto SB, George E, Medvedev S, Simpkins F, Powell DJ. Humanized Patient-Derived Xenograft Models of Ovarian Cancer. Methods Mol Biol. 2022 Jan.2424:255-274. Pubmedid: 34918300.
• Xu H, George E, Kinose Y, Kim H, Shah JB, Peake JD, Ferman B, Medvedev S, Murtha T, Barger CJ, Devins KM, D'Andrea K, Wubbenhorst B, Schwartz LE, Hwang WT, Mills GB, Nathanson KL, Karpf AR, Drapkin R, Brown EJ, Simpkins F. CCNE1 copy number is a biomarker for response to combination WEE1-ATR inhibition in ovarian and endometrial cancer models. Cell Rep Med. 2021 Sep.2(9):100394. Pubmedid: 34622231. Pmcid: PMC8484689.
• Kóder G, Olasz J, Tanyi JL, George E, Tóth L, Antal-Szalmás P, Nagy B, Bubán T, András C, Urbancsek H, Laczik M, Csuka O, Damjanovich L, Tanyi M. Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary. J Gastrointest Cancer. 2020 Sep.51(3):1007-1015. Pubmedid: 31939059. Pmcid: PMC7399673.
• Kim H, Xu H, George E, Hallberg D, Kumar S, Jagannathan V, Medvedev S, Kinose Y, Devins K, Verma P, Ly K, Wang Y, Greenberg RA, Schwartz L, Johnson N, Scharpf RB, Mills GB, Zhang R, Velculescu VE, Brown EJ, Simpkins F. Combining PARP with ATR inhibition overcomes PARP inhibitor and platinum resistance in ovarian cancer models. Nat Commun. 2020 Jul.11(1):3726. Pubmedid: 32709856. Pmcid: PMC7381609.
• Tanyi JL, George E. Personalized vaccination against ovarian cancer: what are the possibilities?. Expert Rev Vaccines. 2018 Nov.17(11):955-958. Pubmedid: 30362844. Pmcid: PMC6592278.
• Kim H, George E, Ragland R, Rafail S, Zhang R, Krepler C, Morgan M, Herlyn M, Brown E, Simpkins F. Targeting the ATR/CHK1 Axis with PARP Inhibition Results in Tumor Regression in BRCA-Mutant Ovarian Cancer Models. Clin Cancer Res. 2017 Jun.23(12):3097-3108. Pubmedid: 27993965. Pmcid: PMC5474193.
• George E, Kim H, Krepler C, Wenz B, Makvandi M, Tanyi JL, Brown E, Zhang R, Brafford P, Jean S, Mach RH, Lu Y, Mills GB, Herlyn M, Morgan M, Zhang X, Soslow R, Drapkin R, Johnson N, Zheng Y, Cotsarelis G, Nathanson KL, Simpkins F. A patient-derived-xenograft platform to study BRCA-deficient ovarian cancers. JCI Insight. 2017 Jan.2(1):e89760. Pubmedid: 28097235. Pmcid: PMC5214535.
• George EM, Burke WM, Hou JY, Tergas AI, Chen L, Neugut AI, Ananth CV, Hershman DL, Wright JD. Measurement and validation of frailty as a predictor of outcomes in women undergoing major gynaecological surgery. BJOG. 2016 Feb.123(3):455-461. Pubmedid: 26301606. Pmcid: PMC4548816.
• Wang Y, Krais JJ, Bernhardy AJ, Nicolas E, Cai KQ, Harrell MI, Kim HH, George E, Swisher EM, Simpkins F, Johnson N. RING domain-deficient BRCA1 promotes PARP inhibitor and platinum resistance. J Clin Invest. 2016 Aug.126(8):3145-3157. Pubmedid: 27454289. Pmcid: PMC4966309.
• George EM, Tergas AI, Ananth CV, Burke WM, Lewin SN, Prendergast E, Neugut AI, Hershman DL, Wright JD. Safety and tolerance of radical hysterectomy for cervical cancer in the elderly. Gynecol Oncol. 2014 Jul.134(1):36-41. Pubmedid: 24768851. Pmcid: PMC4158005.
• George EM, Herzog TJ, Neugut AI, Lu YS, Burke WM, Lewin SN, Hershman DL, Wright JD. Carcinosarcoma of the ovary: natural history, patterns of treatment, and outcome. Gynecol Oncol. 2013 Oct.131(1):42-45. Pubmedid: 23838036. Pmcid: PMC4230696.
• Horvath S, George E, Herzog TJ. Unintended consequences: surgical complications in gynecologic cancer. Womens Health (Lond Engl). 2013 Nov.9(6):595-604. Pubmedid: 24161311.
• Baxi LV, George EM. Three-way tie: the umbilical cord insertion site was different for each member of a set of triplets. Am J Obstet Gynecol. 2013 Dec.209(6):590.e1. Pubmedid: 23665250.
• George EM, Cabreriza SE, Quinn TA, Rusanov A, Gerrah R, Broyles JM, Weinberg AD, Spotnitz HM. Validation of automated monitoring of cardiac output for biventricular pacing optimization. Asaio J. 2010 May.56(3):265-269. Pubmedid: 20335801. Pmcid: PMC5719881.

• Title: Reproductive Scientist Development Program_ABOG
  Sponsor: Amer Board of Obstetrics & Gynecology (ABOG)
  PI: George, E.