My laboratory studies receptor tyrosine kinases as targets for development of anti-cancer therapeutics, with emphasis on the HER/erbB family (EGFR/HER1/erbB1, HER2/erbB2, HER3/erbB3 and HER4/erbB4).  Our early research efforts focused on 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), leading to the approval of Trastuzumab/HERCEPTIN® for use in patients with HER2-positive breast and gastric cancer.  In our original panel of HER2 monoclonal antibodies we discovered a 2nd HER2 antibody which utilizes a different mechanism (inhibition of HER receptor dimerization) than Trastuzumab to elicit anti-tumor activity.  Pertuzumab (PERJETA®) was approved by the US FDA in 2012 for use in HER2-positive breast cancer and in 2013 for neoadjuvant use, the first FDA drug approval for the neoadjuvant setting.  More recently, we developed an antibody-drug conjugate (ADC) comprised of Trastuzumab covalently linked to a potent cytotoxic agent, DM1, for selective delivery of the cytotoxic drug to HER2-overexpressing tumors.  This approach allows targeted delivery of potent cytotoxic agents to tumors while sparing normal tissue.  Trastuzumab emtansine (KADCYLA®, T-DM1) has undergone extensive clinical testing in multiple lines for HER2-positive breast cancer and was FDA-approved in February 2013.  We continue to explore novel methods for targeting different types of HER2-positive cancers.

My role as laboratory director of a translational research lab requires consistent manuscript publication in peer-reviewed journals as well as participation in many external international conferences, including as an invited speaker.  Moreover, my role directing  translational research projects that advanced through clinical trials and marketing approval, allowed me to gain additional experience in clinical development planning; regulatory affairs, including authoring sections of filing applications’ and post-marketing studies, not only in the U.S. but in many countries throughout the world.