Adjunct Faculty

David Michael Epstein

Adjunct Associate Professor


Prior to joining the faculty and Office of Research at Duke-NUS, David M. Epstein was the New York Site-Head, Senior Vice President and Chief Scientific Officer for Oncology Research at OSI Pharmaceuticals, where he was responsible for leading the cancer drug discovery and clinical-translational research efforts conducted by around 140 staff and scientists.   David led OSI's cancer research program from 2006-2013, which was focused on targeting key drivers of cancer development and disease progression.   OSI’s research effort was built upon the foundation provided by the cancer drug erlotinib, an EGFR-directred tyrosine kinase inhibitor, developed and commercialized by OSI, Genentech and Roche in 2004.  Under David’s stewardship, the OSI team developed an oncology pipeline of four novel small molecule kinase inhibitors along with corresponding patient response biomarkers each of which are in various stages of clinical development to treat lung, ovarian, prostate and other cancers.  OSI Oncology Research under David’s mentorship was widely acknowledged for its industry-leading expertise in personalized medicine approaches to cancer care, its numerous academic collaborations, and for uncovering mechanisms through which the mesenchymalization of tumor cells, through the process of epithelial-mesenchymal transition, provides novel routes for resistance to targeted cancer therapies.  OSI was acquired in 2010 by Astellas Pharmaceuticals, and Dr. Epstein led the integration and expansion of the OSI and the NY campus into Astellas-Japan research and global development.
Prior to joining OSI Oncology, David was a principal founder and Vice President of Archemix Corp (2001-2006).  While in this capacity, David facilitated the development of two therapeutic aptamers currently in late-stage clinical development for treating wet and dry macular degeneration.  David has 20 years of leadership experience in both the pharmaceutical and biotechnology industries, leading wide-ranging efforts in oncology, ophthalmic and cardiovascular drug discovery.  
Currently, David provides consulting work to biotech, pharmaceutical and venture capital enterprises, and is involved several early-stage biotech start-ups in the New York area.  
David completed his postdoctoral fellowship in structural biology at The Scripps Research Institute in La Jolla, California, in which he led a collaboration between the laboratories of Dr. Stephen Benkovic (Pennsylvania State University) and Dr. Peter E. Wright: David studied the relationship of protein dynamics to catalysis using the enzyme dihydrolfolate reductase (DHFR).  Specifically, we examined the DHFR-Folate complex by N15 and C13 NMR relaxation dynamics, and utilized the kinetic insights previously developed in the Benkovic lab to build an hypothesis which linked protein dynamics to enzyme catalytic function.  We showed that key aspects of DHFR mechanism and catalytic function could be proscribed by protein motion and dynamics at specific residues and within secondary structural elements.  This work led to the refinement and development of a multi-year collaboration between the Benkovic and Wright labs, which further delineated the relationship between protein dynamics and enzymatic catalysis in DHFR.   David completed his Ph.D. work in The Graduate Department of Biochemistry at Brandeis University under the mentorship of Dr. Robert Abeles, where he studied the mechanism of catalysis of a bacterial elastase which was cloned and then analyzed via the kinetics of mutated enzymes, synthetic substrates, and mechanism-based inhibitors.  David obtained his B.Sc. in Chemistry in 1981 from Lewis & Clark College, a liberal arts college in Portland, Oregon.
We are interested in obtaining a comprehensive molecular and mechanistic understanding of tumor cell mesenchymalization, using clinical specimens and disease models, to further delineate its impact on response to therapy and disease progression. We are interested in delineating robust predictive biomarkers that define drug response in patient populations described currently through various prognostic, yet oncogene-defined biomarkers such as KRas, p53, PTEN.
Richardson,  F., Young, G.D.,  Sennello, R., Wolf, J.,  Argast, G.M., Mercado, P., Davies, A., Epstein, D.M. and Wacker, B., (2012) “The Evaluation of E-cadherin and Vimentin as Biomarkers of Clinical Outcomes Among 2nd- and 3rd- line Non-Small Cell Lung Cancer Patients Treated with Erlotinib,” Anticancer Research, 32: 537 
Zhao, H., Desai, V., Wang, J., Epstein, D.M., Miglarese, M.A., Buck, E., (2012), “Epithelial-Mesenchymal-Transition Predicts Sensitivity to the Dual IGF-1R/IR Inhibitor OSI-906 in Hepatocellular Carcinoma Tumor Cell Lines,” Molecular Cancer Therapeutics, 11: 503.
Bhagwat, S.V., Gokhale, P.C., Crew, A.P., Cooke, A., Yao, Y., Mantis, C.,  Kahler, J., Workman, J., Bittner, M., Dudkin, L., Epstein, D.M., Gibson, N.W., Wild, R., Arnold, L.D., Houghton, P.J., and Pachter, J.A., (2011) “Preclinical Characterization of OSI-027, a Potent and Selective Inhibitor of mTORC1 and mTORC2: Distinct from Rapamycin,” Molecular Cancer Therapeutics, 10: 1394.
Thomson, S., Petti, F., Sujka-Kwok, I., Mercado, .P, Bean, J., Monaghan, M., Seymour, S.L., Argast, G.M., Epstein, D.M., Haley, J.D., (2011) “A systems view of epithelial-mesenchymal transition signaling states,” Clinical & Experimental Metastasis, 28: 137.
Falcon, B., Barr, S, Gokhale, P.C., Chou, J., Fogarty, J., Depeille, P., Miglarese, M., Epstein, D.M., and McDonald, D.M. (2011) “Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors,” Cancer Research, 71: 1573.
Buck, E., Gokhale, P.C., Koujak, S., Brown, E., Eyzaguirre, A., Tao, N., Rosenfeld-Franklin, M., Lerner, L., Chiu, I.M., Wild, R., Epstein, D.M., Pachter, J.A., and Miglarese, M., (2010) “Compensatory Activation of Insulin Receptor (IR) Upon Inhibition of Insulin-Like Growth Factor Receptor (IGF-1R): Rationale for Co-Targeting IGF-1R and IR in Cancer.”  Mol. Cancer, Therapeutics, 9: 2652.
Buck, E., Ezyaguirre, A., Rosenfeld-Franklin, M., Thomson, S., Mulvihill, M., Barr, S., Brown, E., O’Connor, M., Yao, Y., Pachter, J., Miglarese, M., Epstein, D.M., Iwata, K.K., Haley, J.D., Gibson, N.W., and Ji, Q-S. (2008) “Feedback Mechanisms Promote Cooperativity for Small Molecule Inhibitors of Epidermal and Insulin-like Growth Factor Receptors,” Cancer Research, 68: 8322.
Thomson, S., Petti, F., Sujika-Kwok, I., Epstein, D.M., and Haley, J.D. (2008) “Kinase Switching in Mesenchymal-like Non-Small Cell Lung Cancer Lines Contributes to EGFR Inhibitor Resistance Through Pathway Redundancy,” Clinical & Experimental Metastasis, 25: 843.
Sennino, B., Falcon, B.L., McCauley, D., Le, T., McCauley, T., Kurz, J.C., Haskell, A., Epstein, D.M., and McDonald, D.M., (2007) “Sequential Loss of Tumor Vessel Pericytes and Endothelial Cells After Inhibition of PDGF-B By Selective Aptamer AX102,” Cancer Research, 67: 7358.
Burmeister, P.E., Scott, D.L., Preiss, J.R., Silva, R., Horwitz, L.R., Pendergrast, P.S., Kurz, J.C., McCauley, T.G., Epstein, D.M., Wilson, C.W., Keefe, A.D., (2005) “Direct In Vitro Selection of a 2’O-Methyl Aptamer to VEGF,” Chemistry & Biology, 12: 25.
Srinivasan, J., Cload, S.T., Hamaguchi, N., Kurz, J., Keene S., Kurz, M., Boomer, R.M., Blanchard, J., Epstein, D.M., Wilson, C., Diener, J.L., (2004) “ADP-specific sensors enable universal assay of protein kinase activity,” Chemistry & Biology, 11: 499.
Epstein, D.M., Benkovic, S.J., & Wright, P.E., (1995) “Dynamics of the Dihydrofolate Reductase-Folate Complex: Catalytic Sites and Regions Known to Undergo Conformational Change Exhibit Diverse Dynamical Features,” Biochemistry 34: 11037.
Epstein, D.M. & Abeles, R.H., (1992) "The Role of Tyr 171 and Ser 214, Components of the S2 Subsite in -Lytic Protease, in Catalysis," Biochemistry, 31: 11216.