I am a postdoctoral fellow in the labs of Peter Sorger in the Department of Systems Biology and the Laboratory of Systems Pharmacology at Harvard Medical School and Douglas Lauffenburger in the Department of Biological Engineering at Massachusetts Institute of Technology. I am interested in studying the signaling pathways that confer resistance to targeted therapies on melanoma. More specifically the goal of my project is to elucidate the mechanism by which cells which evade apoptosis by entering senescence in the very early stage of drug administration evolve to become proliferative even in the presence of strong inhibition of key intracellular signaling pathways, such as the MAPK cascade.
I received my PhD from Boston University in 2016, where I worked under the supervision of Adrian Whitty. My graduate work has been focused on elucidating the molecular mechanism of signal transduction through the RET receptor tyrosine kinase. In one project, I used two agonist monoclonal antibodies to establish that RET can be stimulated in distinct ways that lead to the distinct cellular outcomes of neuronal differentiation or cell proliferation. Differences in signaling were characterized by measuring both dose-responses and time-courses for RET, ERK and Akt phosphorylation. This work also showed that the canonical ligand-induced RET dimer is required but not sufficient for maximal receptor activation, with higher-order receptor clustering also necessary for a full response. In a second project, I used model-driven data fitting and also computer simulations to elucidate features of the RET activation mechanism. I established that RET participates in the activated receptor complex in a highly cooperative fashion, and that this cooperativity is crucial for the efficient function of receptor systems of this type. I also used computer simulations to explore the functional consequences of whether a homodimeric receptor requires co-receptors for ligand binding, as is the case for RET, compared to simpler systems in which ligand binds to and dimerizes the receptor directly.