Gerold Bepler, M.D., Ph.D.
President & CEO
Karmanos Cancer Institute
4100 John R Detroit, MI 48187
Rhonda Federspiel, B.S.
Executive Assistant to Dr. Bepler
- Discovery, translation, and clinical implementation of molecular markers for cancer diagnosis and treatment.
Dr. Bepler’s research efforts have been focused on the discovery, translation, and clinical implementation of molecular markers for therapeutic decisions in patients with malignancies. In particular, the focus has been on molecules that are involved in efficacy of antimetabolites, such as gemcitabine and pemetrexed, and DNA damaging agents, such as platinum compounds, in lung cancer. Initially, his lab discovered that the regulatory subunit of ribonucleotide reductase (RRM1) was located in a region of frequent allele loss in lung cancer. He was among the first to demonstrate that RRM1 was involved cell proliferation, migration, and invasion and was protective of carcinogen-induced lung tumor formation. His lab was also among the first to demonstrate that RRM1 is the major determinant of gemcitabine efficacy. He conducted the first trial in patient with lung cancer where chemotherapeutic agents were selected based on tumoral levels of RRM1 and ERCC1 expression. These discoveries and approaches are now being applied to other malignancies including but not limited to pancreatic cancer and urothelial malignancies.
Zhang M, Xiang S, Joo HY, Wang L, Williams KA, Liu W, Hu C, Tong D, Haakenson J, Wang C, Zhang S, Pavlovicz RE, Jones A, Schmidt KH, Tang J, Dong H, Shan B, Fang B, Radhakrishnan R, Glazer PM, Matthias P, Koomen J, Seto E, Bepler G, Nicosia SV, Chen J, Li C, Gu L, Li GM, Bai W, Wang H, Zhang X. HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of MutSα. Mol Cell. 2014;55:31-46.
Bepler G, Zinner RG, Moon J, Calhoun R, Kernstine K, Williams CC, Mack PC, Oliveira V, Zheng Z, Stella PJ, Redman MW, Gandara DR. A phase 2 cooperative group adjuvant trial using a biomarker-based decision algorithm in patients with stage I non-small cell lung cancer (SWOG-0720, NCT00792701). Cancer. 2014;120:2343-51.
Patki M, Gadgeel S, Huang Y, McFall T, Shields AF, Matherly LH, Bepler G, Ratnam M. Glucocorticoid receptor status is a principal determinant of variability in the sensitivity of non-small-cell lung cancer cells to pemetrexed. J Thorac Oncol. 2014;9:519-26.
Vaezi AE, Bepler G, Bhagwat NR, Malysa A, Rubatt JM, Chen W, Hood BL, Conrads TP, Wang L, Kemp CE, Niedernhofer LJ. Choline phosphate cytidylyltransferase-α is a novel antigen detected by the anti-ERCC1 antibody 8F1 with biomarker value in patients with lung and head and neck squamous cell carcinomas. Cancer. 2014;120:1898-907.
Zhang Y, Li X, Chen Z, Bepler G. Ubiquitination and degradation of ribonucleotide reductase M1 by the polycomb group proteins RNF2 and Bmi1 and cellular response to gemcitabine. PLoS One. 2014;9:e91186.
Gray JE, Haura E, Chiappori A, Tanvetyanon T, Williams CC, Pinder-Schenck M, Kish JA, Kreahling J, Lush R, Neuger A, Tetteh L, Akar A, Zhao X, Schell MJ, Bepler G, Altiok S. A phase I, pharmacokinetic, and pharmacodynamic study of panobinostat, an HDAC inhibitor, combined with erlotinib in patients with advanced aerodigestive tract tumors. Clin Cancer Res. 2014;20:1644-55.
Chen W, Bepler G. A Method for Biomarker Directed Survival Prediction in Advanced Non-Small-Cell Lung Cancer Patients Treated with Carboplatin-Based Therapy. J Pers Med. 2013;3.
Gadgeel SM, Bepler G. Prognostic and predictive markers for personalized adjuvant therapy for non-small-cell lung cancer patients. Future Oncol. 2013;9:1909-21.
Gadgeel SM, Chen W, Cote ML, Bollig-Fischer A, Land S, Schwartz AG, Bepler G. 9.Fibroblast growth factor receptor 1 amplification in non-small cell lung cancer by quantitative real-time PCR. PLoS One. 2013;8:e79820.
Williams KA, Zhang M, Xiang S, Hu C, Wu JY, Zhang S, Ryan M, Cox AD, Der CJ, Fang B, Koomen J, Haura E, Bepler G, Nicosia SV, Matthias P, Wang C, Bai W, Zhang X. Extracellular signal-regulated kinase (ERK) phosphorylates histone deacetylase 6 (HDAC6) at serine 1035 to stimulate cell migration. J Biol Chem. 2013;288:33156-70
Creelan BC, Antonia S, Bepler G, Garrett TJ, Simon GR, Soliman HH. Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in Stage III non-small cell lung cancer. Oncoimmunology. 2013;2:e23428.
Creelan BC, Antonia S, Noyes D, Hunter TB, Simon GR, Bepler G, Williams CC, Tanvetyanon T, Haura EB, Schell MJ, Chiappori A. Phase II Trial of a GM-CSF-producing and CD40L-expressing Bystander Cell Line Combined With an Allogeneic Tumor Cell-based Vaccine for Refractory Lung Adenocarcinoma. J Immunother. 2013;36:442-50.
Bepler G, Williams C, Schell MJ, Chen W, Zheng Z, Simon G, Gadgeel S, Zhao X, Schreiber F, Brahmer J, Chiappori A, Tanvetyanon T, Pinder-Schenck M, Gray J, Haura E, Antonia S, Fischer JR. Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2013;31:2404-12.
Zhou J, Chen Z, Malysa A, Li X, Oliveira P, Zhang Y, Bepler G. A kinome screen identifies checkpoint kinase 1 (CHK1) as a sensitizer for RRM1-dependent gemcitabine efficacy. PLoS One. 2013;8:e58091.
Education and Training
MD, PhD (1983) Philipps University, Marburg, Germany