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.
Awarded in the Junior Scholar category, Dr. Clark was chosen by the selection committee for his demonstration of great potential by virtue of the quality of his early contributions. His accomplishments, information provided in support of his nomination, and letters of recommendation from well-known authorities in his field demonstrated that he has achieved national and international prominence as an outstanding scholar.
The award recognition ceremony will take place at the 2019 Honors Convocation.
Dr. Takis Benos participated in a collaborative study published in Molecular Cell. The study reports the findings of a “hidden” insulin sensor in the disordered region of SIRT1 protein and the mechanism by which Insulin inhibits SIRT1-mediated catabolic gene expression.
Please click here to read the full article.
Dr. Xing (PI) and Dr. Simon Watkins (co-I) received a R01 award from NIDDK titled Role of the Snail1-Twist-p21 axis on cell cycle arrest and renal fibrosis development.
Kidney fibrosis is slowly-developing, largely irreversible process that accompanies all chronic kidney diseases. The team will use mathematical modeling and quantitative imaging approaches to study how the epithelial-to-mesenchymal transition and cell cycle program are coupled in kidney epithelial cells that lead to cell cycle arrest under acute kidney injury and subsequent fibrosis development.
|Dr. Jianhua Xing
||Dr. Simon Watkins
Dr. Nick Pabon publishes first author paper in PlosCompBio titled: “Predicting protein targets for drug-like compounds using transcriptomics” with Profs. Carlos J. Camacho and Ziv Bar-Joseph.
The paper describes the first method capable of predicting novel drug-target interactions using gene expression profiles. Nick contribution was specially notable in highlighting correlations between profiles indirectly related to the target as the main determinant of physical interactions in the machine learning model.
Read the full paper here