John C. Williams
Molecular Medicine, City of Hope
Using an atoms-up approach, our research efforts have focused on understanding the regulation and activation of biological processes through multivalent interactions. In one line of our investigations, we have developed a series of inducible molecular traps that rapidly antagonize (<mins) molecular interactions involved in endocytosis and cellular trafficking. We have extended the utility of this trapping technology using a photocleavable reagent, allowing us to follow cellular events as they return from acute inhibition. Coupled to microscopy and live cell imaging, these traps provide new insight not currently available with other methods (e.g., siRNA) and will allow us to study molecular events in a single cell in a whole organism. In a second line of investigation, we have developed tumor activated, masked monoclonal antibodies to enhance their efficacy and mitigate their adverse side effects (e.g., cardiac failure). As part of these studies, we have also identified by diffraction methods a novel binding site within a mAb, demonstrated that this interaction does not affect antigen binding, and that this interaction is unique to this specific antibody framework (e.g., does not bind to human mAbs). Collectively, these observations suggest that this interaction can be used as a novel method for drug delivery, imaging, and/or enhance mAb therapeutic efficacy through synergistic coupling. Data will be presented vis-à-vis the design and development of a multivalent imaging agent to realize these goals.
host: Ann McDermott
Thursday, September 8, 2011, 3 pm
NYSBC, 89 Convent Ave (at 133rd Street)
Conference Room A11
