Neel H. Shah

Neel H. Shah

Research Interest

Summary

We are interested in understanding molecular mechanisms in cell signaling, with particular focus on enzymes that phosphorylate and dephosphorylate tyrosine residues on proteins as a means of relaying information within cells. These enzymes, known as protein tyrosine kinases and protein tyrosine phosphatases, constitute two large families of roughly 100 proteins that play crucial roles in normal physiology and are often dysregulated in diseases such as cancers and immunological disorders. As a result, these enzymes are important drug targets.

We integrate chemical approaches with high-throughput biochemical assays, biophysical methods, and cell biology to pinpoint (1) how individual members of these enzyme families have specialized to mediate signal transduction with fidelity, (2) how the dysregulation of phosphotyrosine signaling leads to disease states, and (3) how we might exploit this information to guide the development of novel therapies.

Click here for a complete list of Professor Shah’s publications in PubMed.

  1. Anne E. van Vlimmeren, Rashmi Voleti, Cassandra A. Chartier, Ziyuan Jiang, Deepti Karandur, and Neel H. Shah*. “The pathogenic T42A mutation in SHP2 rewires interaction specificity and enhances signaling.” [preprint] bioRxiv 2023, DOI: 10.1101/2023.07.10.548257
     
  2. Allyson Li, Rashmi Voleti, Minhee Lee, Dejan Gagoski, and Neel H. Shah*. “High-throughput profiling of sequence recognition by tyrosine kinases and SH2 domains using bacterial peptide display.” eLife 2023, 12:e82345
     
  3. Suk ho Hong, Sarah Y. Xi, Andrew C. Johns, Lauren C. Tang, Allyson Li, Marko Jovanovic, and Neel H. Shah*. “Mapping the chemical space of active-site targeted covalent ligands for protein tyrosine phosphatases.” ChemBioChem 2023, 24(10), e202200706.
     
  4. Christopher W. Lamartina, Cassandra A. Chartier, Sumin Lee, Neel H. Shah*, and Tomislav Rovis*. “Modular Synthesis of Unnatural Peptides via Rh(III)-Catalyzed Diastereoselective Three-Component Carboamidation Reaction.” Journal of the American Chemical Society 2023, 145(2) 1129-1135.
     
  5. H. Tomas Rube, Chaitanya Rastogi, Siqian Feng, Judith F. Kribelbauer, Allyson Li, Basheer Becerra, Lucas A. N. Melo, Bach Viet Do, Xiaoting Li, Hammaad H. Adam, Neel H. Shah, Richard S. Mann, and Harmen J. Bussemaker*. “Prediction of protein-ligand binding affinity from sequencing data with interpretable machine learning.” Nature Biotechnology 2022, 40, 1520-1527.
     
  6. Neel H. Shah* and John Kuriyan*. “Understanding molecular mechanisms in cell signaling through natural and artificial sequence variation.” Nature Structural and Molecular Biology 2019, 26, 25-34.