Congratulations to Drs. Nick Pabon and Qiuhong Zhang for their first author paper in Nature Communications titled: A network-centric approach to drugging TNF-induced NF-kB signaling
with Profs. Carlos J. Camacho and Robin E.C. Lee.
Target-centric drug development strategies prioritize single-target potency in vitro and do not account for connectivity and multi-target effects within a signal transduction network. Here, we present a systems biology approach that combines transcriptomic and structural analyses with live-cell imaging to predict small molecule inhibitors of TNF-induced NF-κB signaling and elucidate the network response. We identify two first-in-class small molecules that inhibit the NF-κB signaling pathway by preventing the maturation of a rate-limiting multiprotein complex necessary for IKK activation. Our findings suggest that a network-centric drug discovery approach is a promising strategy to evaluate the impact of pharmacologic intervention in signaling.
Pabon NA, Zhang Q, Cruz JA, Schipper DL, Camacho CJ, Lee REC, (2019). A network-centric approach to drugging TNF-induced NF-κB signaling. Nature Communications. Vol 10, Article number: 860
Dr. Nathan Clark has been selected for the 2019 Chancellor’s Distinguished Research Award which annually recognizes outstanding scholarly accomplishments of members of the University of Pittsburgh’s faculty.