Event

Special Biological Chemistry Seminar at the University of Pennsylvania
 
Dr. Nicholas Till
Stanford University
 
Wednesday, January 15, 2025
10:30 AM
Carolyn Hoff Lynch Lecture Hall
Chemistry Complex
231 South 34th Street
 
 
Mechanism and Technology Development Across Chemistry and Biology 
 
Part I: Visible light photoredox catalysis is a powerful method to modulate small molecule and transition metal reactivity, but we lack insight into the mechanistic basis of this technology. I will present a comprehensive study of an industrially important Nickel/photoredox catalyzed C–N cross-coupling reaction. Using a combination of reaction kinetic analysis, ultrafast spectroscopy, and stoichiometric organometallic studies, we elucidate the key steps in the mechanism of this reaction. We then leverage these insights to design a new photocatalyst yielding improved reaction rate (>30-fold) and quantum yield (>10-fold).
Part II: Targeted degradation of cell surface proteins can address therapeutic challenges rooted in pathologic over-expression or over-activation of a disease-driving protein. Directly introducing cell surface proteins to address therapeutic challenges rooted in pathologic protein deficiency or dysfunction remains an unsolved challenge. I will present the development of bispecific molecules (TrogoTACs) capable of inducing contactdependent protein transfer between cells by redirecting trogocytosis in a targeted fashion. To accomplish this goal, we designed chimeric antibody-small molecule conjugates with specificity to cell surface proteins displaying mutually exclusive expression on donor and acceptor cell types. The protein transfer process is rapid, requires cell-cell contact, and depends on expression of the receptors targeted by the TrogoTAC. Transferred proteins can then redirect T cell engager cytotoxicity to rewire therapeutic targeting towards otherwise unresponsive cancer cells.

 
Bio: Nick Till is an NIH Postdoctoral Fellow in Carolyn Bertozzi's group at Stanford University. He received his PhD in Chemistry from Princeton University in 2021 following studies in photoredox catalysis with David MacMillan. Before graduate school, Nick spent his summers working in the medicinal chemistry departments of Gilead Sciences and Genentech. Nick received his B.A. in chemistry from Reed College in 2016. His research currently focuses on developing new induced proximity modalities to directly manipulate the cell surface proteome.