The ASPIRE Path in Molecular Medicine

The Coffey lab studies a GPI-linked glycoprotein named dipeptidase (DPEP1), with two isoforms (DPEP1 A and DPEP1 B). Currently, there are two known functions – dipeptidase activity and neutrophil binding. There are compounds used clinically that block both functions. During my rotation, I discovered that one of four glycosylation sites in Isoform A of DPEP1 appears to alter its localization from the apical to basolateral surface. I plan on starting my work in the lab by confirming this observation and exploring the consequence of this mislocalization and the underlying mechanism. In the future, I anticipate studying the neoplastic consequences of neutrophils binding to colonic cell surface and EV-bound DPEP1 in the context of early events in colorectal neoplasia using organoids and stem cell-driven mouse models of colon cancer created in the lab. This was one of the major areas of investigation proposed in the TBEL grant, but these studies have not yet started.