"As a translational research scientist, I have the exciting and rewarding position of directing a lab that bridges basic science discoveries with early drug development in Oncology."
I came to Genentech straight out of graduate school to join a lab working on anti-tumor cytokines (TNF-α and IFN-γ). We discovered that activated receptor tyrosine kinases, including HER2, were resistance mechanisms for TNF-α killing of tumor cells. These observations were coincident with the observation that overexpressed HER2 was oncogenic in preclinical models and was a poor prognostic marker in human breast cancer. We then focused our subsequent efforts on elucidating the biology of the HER2 pathway in breast cancer cells and on developing antibody-based therapeutics for HER2-positive cancers.
I direct a tumor cell biology lab that investigates receptor tyrosine kinases as targets for development of anti-cancer therapeutics, with emphasis on the HER/erbB family (primarily HER2/erbB2, with additional efforts on EGFR/HER1/erbB1, HER3/erbB3 and HER4/erbB4). Our early research studies focused on understanding the role of HER2 in HER2-amplified breast cancer, and the biological effects of antibodies directed against HER2. Studies by my lab as well as other laboratories demonstrated antibody-induced inhibition of breast cancer cell growth as a direct function of HER2 expression level. Our lead monoclonal antibody was subsequently humanized for clinical development (one of the first such humanized antibodies put into clinical trials). In our original panel of HER2 monoclonal antibodies we discovered a 2nd HER2 antibody that utilizes a different and novel mechanism, inhibition of ligand-induced HER receptor dimerization, to elicit anti-tumor activity. More recently, we, along with our chemistry colleagues, expanded our efforts in developing therapeutics by designing and investigating different HER2-targeted antibody-drug conjugates, with the goal of delivering highly potent cytotoxic agents selectively to HER2-positive tumor cells. In particular, we perform studies that delve into mechanisms of action of the different therapeutics, as well as mechanisms of innate and acquired resistance. My lab also collaborates with our antibody engineering departments to investigate biology and anti-tumor activity of novel antibody formats, such as bispecific, biepitopic, and dual-specific antibodies.
I have been fortunate to work on translational research projects that resulted in marketing approval of several breast cancer therapies. As such, I have had the opportunity for cross-functional collaborations which allowed me to learn aspects of drug development (pharmacokinetics, analytical assays, safety assessment, clinical trial design, regulatory filings) outside my area of research expertise. After several decades at Genentech, I am still excited to come to work every day. Genentech is a highly collaborative, team-oriented, fast-paced and fun-filled environment. It is a privilege to work with such smart, passionate people who strive every day to make a difference in the lives of patients.