Neel H. Shah
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.
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. ChemRxiv 2022, https://doi.org/10.26434/chemrxiv-2022-1rnqh
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.” bioRxiv 2022, https://doi.org/10.1101/2022.08.01.502334
Helen T. Hobbs, Neel H. Shah, Sophie R. Shoemaker, Jeanine F. Amacher, Susan Marqusee, and John Kuriyan*. “Saturation mutagenesis of a predicted ancestral Syk-family kinase.” Protein Science 2022, 31, e4411.
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.
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.
Wan-Lin Lo, Neel H. Shah, Sara A. Rubin, Weiguo Zhang, Veronika Horkova, Ian R. Fallahee, Ondrej Stepanek, Leonard Zon, John Kuriyan, and Arthur Weiss*. “Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination.” Nature Immunology 2019, 20, 1481-1493.
Neel H. Shah, Mark Löbel, Arthur Weiss, and John Kuriyan*. “Fine-tuning of substrate preferences of the Src-family kinase Lck revealed through a high-throughput specificity screen.” eLife 2018, 7, e35190.
Pradeep Bandaru, Neel H. Shah, Moitrayee Bhattacharyya, John P. Barton, Yasushi Kondo, Joshua C. Cofsky, Christine L. Gee, Arup K. Chakraborty, Tanja Kortemme, Rama Ranganathan*, and John Kuriyan*. “Deconstruction of the Ras switching cycle through saturation mutagenesis.” eLife 2017, 6, e27810.
Neel H. Shah, Qi Wang, Qingrong Yan, Deepti Karandur, Theresa A. Kadlecek, Ian R. Fallahee, William P. Russ, Rama Ranganathan, Arthur Weiss, and John Kuriyan*. “An Electrostatic Selection Mechanism Controls Sequential Kinase Signaling Downstream of the T Cell Receptor.” eLife 2016, 5, e20105.