Karmanos Cancer Institute
4100 John R
Detroit, MI 48201
Research InterestsDiscovery, 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.
Camidge DR, Moran T, Demedts I, Grosch H, Mileham K, Molina J, Juan-Vidal O, Bepler G, Goldman JW, Park K, Wallin J, Wijayawardana SR, Wang XA, Wacheck V, Smit E. A Randomized, Open-Label Phase II Study Evaluating Emibetuzumab Plus Erlotinib and Emibetuzumab Monotherapy in MET Immunohistochemistry Positive NSCLC Patients with Acquired Resistance to Erlotinib. Clin Lung Cancer. 2022;23:300-10.
Nagasaka M, Singh V, Baca Y, Sukari A, Kim C, Mamdani H, Spira AI, Uprety D, Bepler G, Kim ES, Raez LE, Pai SG, Ikpeazu C, Oberley M, Feldman R, Xiu J, Korn WM, Wozniak AJ, Borghaei H, Liu SV. The Effects of HER2 Alterations in EGFR Mutant Non-small Cell Lung Cancer. Clin Lung Cancer. 2022;23:52-9.
Bollig-Fischer A, Bao B, Manning M, Dyson G, Michelhaugh SK, Mittal S, Bepler G, Mamdani H. Role of novel cancer gene SLITRK3 to activate NTRK3 in squamous cell lung cancer. Mol Biomed. 2021;2:26.
Zhang XM, Gavande N, Parajuli P, Bepler G. Implications of the USP10-HDAC6 axis in lung cancer - A path to precision medicine. J Cancer Biol. 2021;2:10.46439/cancerbiology.2.015.
Nagasaka M, Asad MFB, Al Hallak MN, Uddin MH, Sukari A, Baca Y, Xiu J, Magee D, Mamdani H, Uprety D, Kim C, Xia B, Liu SV, Nieva JJ, Lopes G, Bepler G, Borghaei H, Demeure MJ, Raez LE, Ma PC, Puri S, Korn WM, Azmi AS. Impact of XPO1 mutations on survival outcomes in metastatic non-small cell lung cancer (NSCLC). Lung Cancer. 2021;160:92-8.
Hu C, Zhang M, Moses N, Hu CL, Polin L, Chen W, Jang H, Heyza J, Malysa A, Caruso JA, Xiang S, Patrick S, Stemmer P, Lou Z, Bai W, Wang C, Bepler G, Zhang XM. The USP10-HDAC6 axis confers cisplatin resistance in non-small cell lung cancer lacking wild-type p53. Cell Death Dis. 2020;11:328.
Moses N, Zhang M, Wu JY, Hu C, Xiang S, Geng X, Chen Y, Bai W, Zhang YW, Bepler G, Zhang XM. HDAC6 Regulates Radiosensitivity of Non-Small Cell Lung Cancer by Promoting Degradation of Chk1. Cells. 2020;9:2237.
Beebe-Dimmer JL, Ruterbusch JJ, Harper FWK, Baird TM, Finlay DG, Rundle AG, Pandolfi SS, Hastert TA, Schwartz KL, Bepler G, Simon MS, Mantey J, Abrams J, Albrecht TL, Schwartz AG. Physical activity and quality of life in African American cancer survivors: The Detroit Research on Cancer Survivors study. Cancer. 2020;126:1987-94.
Zhang M, Hu C, Moses N, Haakenson J, Xiang S, Quan D, Fang B, Yang Z, Bai W, Bepler G, Li GM, Zhang XM. HDAC6 regulates DNA damage response via deacetylating MLH1. J Biol Chem. 2019;294:5813-26.
Heyza JR, Lei W, Watza D, Zhang H, Chen W, Back JB, Schwartz AG, Bepler G, Patrick SM. Identification and Characterization of Synthetic Viability with ERCC1 Deficiency in Response to Interstrand Crosslinks in Lung Cancer. Clin Cancer Res. 2019;25:2523-36.
Lusk CM, Watza D, Dyson G, Craig D, Ratliff V, Wenzlaff AS, Lonardo F, Bollig-Fischer A, Bepler G, Purrington K, Gadgeel S, Schwartz AG. Profiling the Mutational Landscape in Known Driver Genes and Novel Genes in African American Non-Small Cell Lung Cancer Patients. Clin Cancer Res. 2019;25:4300-8.
Chiappori AA, Williams CC, Gray JE, Tanvetyanon T, Haura EB, Creelan BC, Thapa R, Chen DT, Simon GR, Bepler G, Gabrilovich DI, Antonia SJ. Randomized-controlled phase II trial of salvage chemotherapy after immunization with a TP53-transfected dendritic cell-based vaccine (Ad.p53-DC) in patients with recurrent small cell lung cancer. Cancer Immunol Immunother. 2019;68:517-27.
MD, PhD (1983) Philipps University, Marburg, Germany