President & CEO, Joint Membership with MID
Rhonda Federspiel, B.S.
Executive Assistant to Dr. Bepler
Karmanos Cancer Institute
4100 John R Detroit, MI 48187
DepartmentKarmanos Cancer Institute
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.
Kim D, Sun M, He L, Zhou QH, Chen J, Sun XM, Bepler G, Sebti SM, Cheng JQ. A small molecule inhibits Akt through direct binding to Akt and preventing Akt membrane translocation. J Biol Chem. 2016;291:22856. Farrell JJ, Moughan J, Wong JL, Regine WF, Schaefer P, Benson AB 3rd, Macdonald JS, Liu X, Yen Y, Lai R, Zheng Z, Bepler G, Guha C, Elsaleh H. Precision Medicine and Pancreatic Cancer: A Gemcitabine Pathway Approach. Pancreas. 2016;45:1485-93. Arora S, Heyza J, Zhang H, Kalman-Maltese V, Tillison K, Floyd AM, Chalfin EM, Bepler G, Patrick SM. Identification of small molecule inhibitors of ERCC1-XPF that inhibit DNA repair and potentiate cisplatin efficacy in cancer cells. Oncotarget. 2016;7:75104-17. Beaver C, Magnan MA, Henderson D, DeRose P, Carolin K, Bepler G. Standardizing Assessment of Competences and Competencies of Oncology Nurses Working in Ambulatory Care. J Nurses Prof Dev. 2016;32:64-73. Zhang M, Hu C, Tong D, Xiang S, Williams K, Bai W, Li GM, Bepler G, Zhang X. Ubiquitin-specific Peptidase 10 (USP10) Deubiquitinates and Stabilizes MutS Homolog 2 (MSH2) to Regulate Cellular Sensitivity to DNA Damage. J Biol Chem. 2016;291:10783-91. Bell EH, Chakraborty AR, Mo X, Liu Z, Shilo K, Kirste S, Stegmaier P, McNulty M, Karachaliou N, Rosell R, Bepler G, Carbone DP, Chakravarti A. SMARCA4/BRG1 Is a Novel Prognostic Biomarker Predictive of Cisplatin-Based Chemotherapy Outcomes in Resected Non-Small Cell Lung Cancer. Clin Cancer Res. 2016;22:2396-404. Zheng SD, Bui K, Chiappori A, Bepler G, Bui MM. RRM1, ERCC1 and TS1 Immunofluorescence Expression in Leiomyosarcoma: A Tissue Microarray Study with Clinical Outcome Correlation Analysis. Pathol Oncol Res. 2016;22:477-82.
MD, PhD (1983) Philipps University, Marburg, Germany