Investigators

Summary

The main interest of the Neumann laboratory is to expand our knowledge of cell signaling that is in part mediated by oxidation and reducing (redox) reactions as reactive oxygen species (ROS) deregulate the redox homeostasis and promote tumor formation by initiating an aberrant induction of signaling networks that cause tumorigenesis, including breast cancer. To investigate the specific mechanisms underlying redox-induced tumorigenesis, the Neumann laboratory focuses on the redox-induced posttranslational modifications (PTM) of protein cysteines, which are essential in cell signaling. Peroxiredoxin 1 (PRDX1) is a peroxidase that has emerged as a critical protein in cell signaling as it scavenges the second messenger H2O2, binds to and regulates signaling proteins, and when knocked out in mice, causes a variety of cancers, including breast cancer. 

Using this system, we have identified protein cysteines modified by ROS, contributing to breast cancer initiation and progression. For example, we have discovered that a previously unknown functionally essential cysteine in the recombinase RAD51 is vital for its function in homologous recombination-mediated DNA repair. Based on these findings, we have developed a reversible, non-toxic covalent inhibitor that targets this functionally essential RAD51 cysteine, thus inhibiting RAD51 function and, significantly, sensitizing triple-negative breast cancer cells to DNA-damaging therapies. Current work in the laboratory is geared towards successfully  IND-labeling the inhibitor and further discovering other functional protein cysteine targets that can be exploited as anti-cancer therapies.