2015 Early Career Investigator Grant Recipient — Kris Wood, PhD

Project Summary

Most ovarian cancer deaths (~70%) occur in patients with advanced, high-grade serous ovarian cancer (HGS-OvCa). Standard treatment for this disease, which includes surgery plus chemotherapy, yields long-term (5+ year) remissions in only around 30% of patients. The majority of deaths from HGS-OvCa are caused when the disease eventually fails to respond to chemotherapy. It is clear, therefore, that in order to improve patient outcomes, we must develop chemotherapeutic strategies that more consistently and durably eliminate disseminated, recalcitrant disease. Unfortunately, doing this is a challenge, as we know that individual tumors can activate a range of growth- and survival-promoting processes that allow them to survive the otherwise lethal effects of chemotherapy.

Recently, my laboratory developed a pair of companion methods that we collectively refer to as “Oncopathway Profiling”. These methods enable us, for the first time, to rapidly and systematically identify the specific processes that cancer cells use to overcome the toxicity of chemotherapies and then design new therapies that reverse these processes, synergistically enhancing chemotherapeutic efficacy. Already, we have demonstrated the power of Oncopathway Profiling in studies involving a range of diverse cancer types and drugs, studies which have led to both new insights into the biological mechanisms governing chemotherapeutic response as well as the design of improved combination therapies with enhanced selectivity and potency.

In this proposal, we describe the use of Oncopathway Profiling to identify combination therapies to improve the responses of HGS-OvCa patients to both existing, approved “cytotoxic” chemotherapeutics as well as a set of emerging new “targeted” therapies. We describe a pipeline for identifying key biological mechanisms governing response to these drugs, followed by the in-depth credentialing of multiple strategies to reverse these mechanisms and ultimately the validation of these strategies in HGS-OvCa cell lines and animal models. This work extends from my laboratory’s strong interests in women’s cancers and leverages our existing collaborations with well-established ovarian cancer clinicians and researchers at Duke University. If successful, the work described in this proposal will serve as a springboard for the clinical translation of new, improved therapeutic strategies to improve the outcomes of patients with HGS-OvCa.

Bio

Kris C. Wood, Ph.D., is an Assistant Professor in the Department of Pharmacology and Cancer Biology at Duke University.  He received his B.S. degree in Chemical Engineering from the University of Kentucky, where he was recognized with the outstanding sophomore, junior, and senior awards in Chemical Engineering, the Tau Beta Pi outstanding senior award in the College of Engineering, and a Barry M. Goldwater scholarship in science and mathematics.  He received his Ph.D. in Chemical Engineering from the Massachusetts Institute of Technology, where he developed self-assembling polymeric systems for controlled gene and drug delivery under the supervision of Professors Paula Hammond, Ph.D. and Robert Langer, Sc.D.  As an NIH and Misrock Fund postdoctoral fellow in the laboratory of David Sabatini, M.D., Ph.D. at the Whitehead Institute for Biomedical Research and the Broad Institute of Harvard and MIT, his work focused on the development of functional genomic tools to study the determinants of anticancer drug sensitivity. Dr. Wood’s lab at Duke uses new functional and computational genomic approaches to identify novel tumor vulnerabilities and strategies for circumventing therapeutic resistance. He has received the Liz Tilberis Early Career Award from the Ovarian Cancer Research Alliance, Scholar Awards from the V Foundation, Stewart Trust, Forbeck Foundation, Whitehead Foundation, and the NIH BIRCWH Program, and research awards from the Lloyd Trust, Golfers Against Cancer, NIH, and American Association for Cancer Research.   Read a short Q&A with Dr. Wood