Neel H. Shah

Neel H. Shah

Research Interest

Biological
Organic

Summary

The overarching focus of our lab is to understand, at the molecular level, how information is relayed through human cells through the actions of specific proteins, and to discern how aberrations to the structures of those proteins can disrupt normal cellular processes and lead to diseases. We primarily focus on cell signaling enzymes that phosphorylate and dephosphorylate tyrosine residues on proteins as a means of relaying information within cells. These enzymes, known as tyrosine kinases and 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, immune disorders, and developmental disorders. As a result, these enzymes are important drug targets.

To investigate cell signaling, we integrate chemical approaches with high-throughput biochemical assays, biophysical methods, and cell biology/proteomics. We uses these approaches to understand (1) how signaling proteins engage in selective molecular recognition, (2) how they are regulated through conformational changes, and (3) how mutations impact their structure, activity, and interactions to cause human diseases. Finally, our lab aims to use this information to guide the development of novel molecules that modulate signaling protein function.

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

  1. Anne E. van Vlimmeren, Lauren C. Tang, Ziyuan Jiang, Abhishek Iyer, Rashmi Voleti, Konstantin Krismer, Jellert T. Gaublomme, Marko Jovanovic, and Neel H. Shah*. “Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.” [preprint] bioRxiv 2025, DOI: 10.1101/2025.02.26.640373
  2. Anne E. van Vlimmeren†, Ziyuan Jiang†, Deepti Karandur, Anya T. Applebaum Licht, and Neel H. Shah*. “The pathogenic E139D mutation stabilizes a non-canonical active state of the multi-domain phosphatase SHP2.” Protein Science 2025, 34(12):e70373.
  3. Dejan Gagoski†, H. Tomas Rube†, Chaitanya Rastogi, Lucas Melo, Xiaoting Li, Rashmi Voleti, Neel H. Shah*, and Harmen J. Bussemaker*. “Accurate affinity models for SH2 domains from peptide binding assays and free-energy regression.” Protein Science 2025, 34(11):e70317.
  4. Ziyuan Jiang, Anne E. van Vlimmeren, Deepti Karandur, Alyssa Semmelman, and Neel H. Shah*. “Deep mutational scanning of a multi-domain signaling protein reveals mechanisms of regulation and pathogenicity.” Nature Communications 2025, 16, 5464.
  5. Cassandra A. Chartier, Virgil A. Woods, Yunyao Xu, Anne E. van Vlimmeren, Andrew C. Johns, Marko Jovanovic, Ann E. McDermott, Daniel A. Keedy, and Neel H. Shah*. “Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction.” Protein Science 2025, 34(1), e70016.
  6. Christopher W. Lamartina, Cassandra A. Chartier, Jillian M. Hirano, Neel H. Shah*, and Tomislav Rovis*. “Crafting Unnatural Peptide Macrocycles via Rh(III)-Catalyzed Carboamidation.” Journal of the American Chemical Society 2024, 146(30), 20868-20877.
  7. David C. Cabanero†, Stavros K. Kariofillis†, Andrew C. Johns, Jinwoo Kim, Jizhi Ni, Sangho Park, Dann L. Parker, Jr., Carlo Ramil, Xavier Roy, Neel H. Shah*, and Tomislav Rovis*. “Photocatalytic Activation of Aryl(trifluoromethyl) Diazos to Carbenes for High-Resolution Protein Labeling with Red Light.” Journal of the American Chemical Society 2024, 146(2), 1337-1345.
  8. Anne E. van Vlimmeren†, Rashmi Voleti†, Cassandra A. Chartier, Ziyuan Jiang, Deepti Karandur, Preston A. Humphries, Wan-Lin Lo, and Neel H. Shah*. “The pathogenic T42A mutation in SHP2 rewires the interaction specificity of its N-terminal regulatory domain.” Proceedings of the National Academy of Sciences 2024, 121(30) e2407159121.
  9. 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.