Dennis E. Hourcade, PhD, MA

Professor of Medicine

Washington University in St. Louis (WU)

1. The complement system is a first line of defense of the intravascular space: Complement rapidly recognizes foreign entities and marks them for clearance and/or lysis. Many pathogens have evolved systems to avoid complement-activity. We are focusing on novel strategies to direct complement-dependent clearance of complement-resistant and antibiotic-resistant Gram-negative bacteria.
2. We are very interested understanding the mechanism of Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations (RVCL-S), a rare monogenic condition that results in late onset cognitive and visual dysfunction and death. RVCL-S is caused by dominant frameshift mutations in Trex1, a gene that encodes a 3′ DNA exonuclease normally tethered to the ER with the nuclease domain facing the cytosol. The RVCL-S associated mutations produce a functional exonuclease that is misplaced in the cell nucleus and likely impairs the DNA damage response and genome stability.