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Zach completed his PhD in Biochemistry at the University of Oklahoma in the lab of Dr. Anthony W.G. Burgett. His dissertation research employed cutting-edge techniques at the interface of cellular biology, protein biochemistry, and chemical genetics to understand new cellular processes in lipid biology, innate immunity, and cell signaling.
This work focused on characterizing the cellular activity of bioactive natural products targeting oxysterol sterol binding proteins (OSBP), a class of proteins emerging as attractive therapeutic targets due to their previously unrecognized roles in various diseases including cancer and viral replication. Utilizing these molecules as biological probes, he discovered critical insights into cancer and antiviral biology, including an unrecognized role in mTORC1 regulation. These insights were leveraged to develop the first OSBP-directed prophylactic broad-spectrum antiviral therapeutic approach. The evolutionarily conserved viral dependence on OSBP as a host factor indicates that this approach may be effective against viruses that have not yet emerged, and could be an important tool for rapidly combating future pandemics. For this work, Zach was awarded the Bullard Dissertation Completion Fellowship which is awarded to the top doctoral dissertations at the University of Oklahoma each year. Zach is also passionate about teaching and scientific communication, resulting in numerous teaching awards during his time at OU, including a 3x awardee of the Provost’s Certificate of Distinction in Teaching.
After completing his PhD, he joined Dr. Amit Choudhary’s lab at the Broad Institute of MIT and Harvard as a Postdoctoral Associate and MIT affiliate researcher. His postdoctoral research focused on the development of new classes of bifunctional molecules using DNA-encoded library (DEL) screening. These bifunctional molecules induce synthetic proximity between an effector and target of interest to enable direct protein editing (e.g., phosphorylation), or direct recruitment of immune components to pathogens. During this time, Zach led a team of researchers in a high-impact DARPA project exploring novel proximity-induction mechanisms for targeting multidrug resistance pathogens. Working closely with the Schreiber lab, he implemented a DEL screening platform that led to the discovery of chemical matter against immune and pathogen surface proteins that were previously unamendable to bifunctional recruitment. Secondly, his postdoctoral research focused on the use of CRISPR-Cas based directed evolution to evolve proteins with enhanced functions and study drug resistance to better understand drug resistance development against bifunctional molecules compared to traditional inhibitors.
Zach is now a scientist at General Proximity where he works with the Platform and Biology Teams to help develop next generation proximity-inducing therapeutics. In his free time, Zach enjoys spending time with his family, reading, camping, sports, and horror movies.
