The goal of my research lab is to combine computation and experiment to design and develop improved molecular therapeutics. A major theme is to rationally manipulate molecules to yield desired cellular responses that can translate into beneficial effects at the level of the whole body. To this end, we take a systems approach to analyzing cellular processes. With this quantitative analysis, design criteria for enhancing the efficacy of therapeutics are identified and then achieved using methods, such as molecular modeling and site-directed mutagenesis. One of our projects involves increasing the lifetimes of therapeutics in the body to decrease the frequency of injections while simultaneously lowering drug dosage. Researchers are addressing this challenge by conjugating therapeutics to the Fc fragment of immunoglobulin G (IgG), since the Fc fragment is responsible for IgG’s long half-life in the body. To further engineer the Fc fragment, we have combined mass action kinetics with statistical mechanics to develop a mathematical model to describe the trafficking behavior of the Fc fragment. The goal of another one of my projects is to improve the design of transferrin (Tf), since it has been used to selectively deliver cytotoxins to cancer cells. This approach has the potential for reducing the unwanted killing of normal cells, and through mathematical modeling of cellular processes, a new design criterion has been identified. Tf mutants that satisfy this design criterion have been made using site-directed mutagenesis, radiolabeled with iodine-125, and their cell-level behavior measured in HeLa cells.
Copyright. All Rights Reserved.