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.
Neel H. Shah and Adam J. Stevens. “Identification, Characterization, and Optimization of Split Inteins.” Methods in Molecular Biology, (2020), 2133, 31-54.
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.
Neel H. Shah, Ertan Eryilmaz, David Cowburn, and Tom W. Muir. “Naturally Split Inteins Assemble through a ‘Capture and Collapse’ Mechanism.” Journal of the American Chemical Society (2013), 135, 18673-18681.
Neel H. Shah, Geoffrey P. Dann, Miquel Vila-Perelló, Zhihua Liu, and Tom W. Muir. “Ultrafast Protein Splicing is Common among Cyanobacterial Split Inteins.” Journal of the American Chemical Society (2012), 134, 11338-11341.