I think drugs are super awesome. Among hundred of other uses, they can alleviate pain, stop diarrhea, alter your state-of-mind, and treat cancer. I have been interested in how drugs affect the body since I was young, and have been conducting drug-related research activities for the past decade.

My research mentality

“Structure determines function.” A simple phrase that describes a central biological concept. In deference to this mantra, the overarching goal of my research career is to dissect how structural movements of proteins modulate function, and to apply this understanding to improving therapeutics for treatment of human disease. My unique background, which combines industrial training in protein purification and molecular biology with graduate training in innovative biophysical techniques, has given me the tools necessary to understand proteins as living, “breathing” molecules, with dynamic structural movements that drive their function.

Research institutions

University of Minnesota, Twin Cities

Structural biophysics with protein kinases in the Levinson Laboratory

I completed my graduate studies in the Levinson Laboratory, where I used biophysics to study allosteric mechanisms that regulate protein kinases, key signaling enzymes. Broadly, we wanted to understand how modulation of kinase dynamics (how the protein "moves") can lead to improved therapeutics. We sought to develop strategies to quantify the relationships between conformational dynamics and drug selectivity in protein kinases.

Off-target effects are a general problem with kinase inhibitors

Generally, kinase inhibitors target the active-site, which is completely conserved in all of the over 500 known protein kinase in the Human Kinome, and therefore, produce many side-effects when used in the clinic. Gleevec,which treats Chronic Myelogenous Leukemia (CML), is at present, the most clinically successful kinase inhibitor, and its success is due to its remarkable selectivity. As shown in the kinome graphic below (red dots indicate a targeted kinase), Gleevec targets only a small number of kinases as compared to another inhibitor, VX-680, which targets many.

A core hypothesis of the Levinson Lab is that selectivity of kinase inhibitors is due to differences in the conformational dynamics ("movement") of each protein kinase, and that discovering the relationship between dynamics and inhibitor binding will help to guide future drug development efforts that exploit conformational dynamics to gain selectivity.

University of Wisconsin, Madison

Molecular Imaging and Targeted Therapeutics in the LeBeau Laboratory

As acting lab manager, I moved and started the lab at the University of Wisconsin, Madison for Dr. LeBeau. UW Madison is a leader in nuclear imaging technology, a core driver of the lab, and had extensive support facilities for the research we conducted.

In addition to my lab manager duties, I used bio-panning, a directed-evolution methodology, to create novel nano- and anti-bodies to target proteins involved in prostate cancer and other diseases. These antibodies could eventually be used as both diagnostic and therapeutic options for the treatment of advanced stages of prostate cancer. I also helped to pioneer the use of Nurse sharks for the creation of biased nanobody libraries. These sharks were housed in a facility on campus, and I led care, feeding, and procedures for these animals.

I also purified one of LeBeau's key target proteins, Fibroblast Activating Protein (FAP), to discover the binding locations of our in-development nanobodies derived from our nurse sharks. I learned to use cryo-EM for this investigation in collaboration with a graduate student in Dr. Tim Grant's lab.