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Lab News
2025
April 2025 – Congratulations to Katherine Hebert and Loren Cardani for completing their 2nd year defenses!
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April 2025 – We’re excited to share that our lab received an NSF CAREER Award from the Division of Chemistry to study sequence recognition in cell signaling enzymes.
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March 2025 – Check out our latest preprint entitled “Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.” This work was led by graduate student Anne van Vlimmeren, with contributions from lab members Jason Jiang and Rashmi Voleti, and collaborators in the Jovanovic and Gaublomme labs at Columbia Biological Sciences. In this study, we used TurboID proximity labeling to examine how structurally and functionally distinct disease-associated mutations in SHP2, as well as allosteric inhibitor binding, alter this phosphatase’s protein-protein interactions and localization. We show that different pathogenic mutations reshape the interactome in distinct ways, and allosteric inhibition broadly reduces protein-protein interactions. Furthermore, our experiments show that SHP2 has extensive interactions with mitochondrial proteins and some mutants have enhanced mitochondrial localization that could contribute to their pathogenicity. We propose a molecular mechanism underlying the changes in mitochondrial localization by different SHP2 mutants.
February 2025 – We’re pleased to share this new preprint from Xin Zhang’s lab at CUIMC, with contributions from Jason Jiang in our group, entitled “Allosteric inhibition rescues hydrocephalus caused by catalytically inactive Shp2.” This study describes a unique developmental phenotype, hydrocephalus, in mice expressing a catalytically dead SHP2 variant, caused by an enhancement in its non-catalytic binding and scaffolding functions.
January 2025 - We're happy to share a recent publication that we contributed to, driven by our collaborators in Marko Jovanovic's lab at Columbia Biological Sciences, entitled "SEC-MX: an approach to systematically study the interplay between protein assembly states and phosphorylation." The study, published in Nature Communications, describes a novel multiplexed mass spectrometry proteomics method that combines size-exclusion-based fractionation and phosphoproteomics to identify protein complexes and infer their phosphorylation states.
January 2025 - We’re excited to welcome Annalise Scorzari to our group as the newest graduate student from the Columbia Chemistry PhD program!
2024
December 2024 - We're excited to see Cassie's paper on the allosteric regulation of the phosphatase PTP1B by the adaptor protein Grb2 published in its final form in Protein Science!
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December 2024 - Check out our latest preprint, in close collaboration with Harmen Bussemaker's group in Columbia Biological Sciences, entitled "Accurate sequence-to-affinity models for SH2 domains from multi-round peptide binding assays coupled with free-energy regression." This paper was driven by joint Shah/Bussemaker postdoc Dejan Gagoski and former Bussemaker group postdoc Tomas Rube. We show that the machine learning method Probound, previously developed by the Bussemaker group, can interpret data from multi-round selection and deep sequencing assays on naive peptide libraries, determine binding register, account for nonspecific binding, and predict relative affinities and binding free energies in a way that is not dependent on library composition. We examine a handful of SH2 domains as a case study. Our analyses reveal subtle differences between highly homologous SH2 paralogs, and we predict new proteome-wide SH2 binding sites and the effects of phosphosite-proximal allelic variants.
October 2024 - Congrats to Loren on becoming a member of the Columbia GSAS Office of Academic Diversity and Inclusion Student Delegation.
July 2024 - Congrats to Dr. Cassandra Chartier, the newest PhD from our lab! Cassie’s thesis was entitled, “Regulation of tyrosine phosphatases thorugh protein-protein interactions.” Cassie is heading to D.C. this fall to be a AAAS Science & Technology Policy Fellow.
​July 2024 - Our newest preprint, entitled “Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction”, just dropped! This work, which was pioneered by Cassie Chartier, describes how the ubiquitous adaptor protein, Grb2, binds to PTP1B and enhances its catalytic activity. We look at this interaction through a suite of biochemical, biophysical, and cellular assays, and we also use proteomics to identify other interactors of PTP1B that might regulate its activity via a similar mechanism.
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July 2024 - Check out our newest collaboration with the Rovis lab, entitled “Crafting Unnatural Peptide Macrocycles via Rh(III)-Catalyzed Carboamidation”. This work was spearheaded by Chris Lamartina in the Rovis lab, with awesome collaborations from Cassie Chartier in our group and Jillian Hirano in the Rovis lab. Here, we expand the scope of our previously reported Rh(III)-catalyzed peptide ligation strategy to the modular construction of structurally diverse macrocyclic peptides.
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July 2024 - Anne’s and Rashmi’s paper on how the T42A mutation in SHP2 rewires interaction specificity and enhances signaling was published in its final form at PNAS!
June 2024 - Congrats to Zijing, Yethmie, and Anya on all being accepted into the Barnard Summer Research Institute!
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June 2024 - We’re happy to recruit three new members to the Shah Lab this month: Dr. Devon Semoy, our newest postdoc, joins us after completing his PhD in Biochemistry at CUNY. Yethmie Goonatilleke and Ayna Applebaum Licht, the newest undergraduates to join the lab, come to us from Barnard College!
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May 2024 - We’re excited to share our latest preprint, entitled “Revealing the principles of inter- and intra-domain regulation in a signaling enzyme via scanning mutagenesis”. In this study, pioneered by Ziyuan (Jason) Jiang, with contributions from Anne van Vlimmeren, Alyssa Semmelman, and computational collaborator Deepti Karandur, we reveal new details of the allosteric regulation of the tyrosine phosphatase SHP2. These insights come from a series of deep mutational scanning experiments as well as molecular dynamics simulations. This work lays the foundation for tons of new studies into SHP2 structure and dynamics, and phosphatase allostery and enzymatic activity in general.
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May 2024 - Congrats to Madeleine Hum on her graduation from Columbia College with a Bachelor’s degree in Applied Mathematics!
May 2024 - We’re so proud of Minhee and Cassie on receiving two amazing departmental awards! Minhee received the Chemistry Department's Arun Guthikonda Fellowship, awarded to a student in organic or biological chemistry in recognition of their distinguished achievements and potential. Cassie received the departmental service award, for her many contributions to uplifting and supporting our committee.
March 2024 - Congratulations to Cassie on being selected for the prestigious AAAS Congressional Policy Fellowship!
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January 2024 - We're excited to highlight our collaboration with co-first authors David Cabanero and Stavros Kariofillis from the Rovis lab, Andrew Johns from our group, and researchers at Merck, recently published in JACS. In this paper, entitled, "Photocatalytic Activation of Aryl(trifluoromethyl) Diazos to Carbenes for High-Resolution Protein Labeling with Red Light", we show that carbenes can be generated from diazo molecules using a red-light-activated osmium catalyst. The resulting reactive species is short-lived and can label proteins more selectively than long-lived nitrenes that have previously been generated via red-light photocatalysis. We envision that this will be a powerful new tool for high-resolution photo-proximity labeling in complex biological environments.
2023
December 2023 - We're excited to welcome Katherine Hebert and Loren Cardani to our group as the newest graduate students from the Columbia Chemistry PhD program!
November 2023 - Congrats to Andrew and Minhee on passing their 4th year Original Research Proposals!
September 2023 - We're excited to welcome Dr. Komal Mandal as the newest postdoctoral researcher in our group!
August 2023 - We're excited to announce that our lab just received funding from the NCI Innovative Molecular Analysis Technologies program to develop new strategies to identify the substrates of cancer-relevant protein tyrosine phosphatases!
July 2023 - Congrats to Andrew Johns for winning a Best Poster award at The Protein Society Annual Symposium for his really exciting work on mapping phosphatase interactions using photocrosslinking!
July 2023 - Congratulations to first-authors Anne and Rashmi, and the whole SHP2 subgroup, on their new preprint in bioRxiv entitled, "The pathogenic T42A mutation in SHP2 rewires ligand binding specificity and enhances signaling." In this paper, we explore how five mutations in the SH2 domains of the tyrosine phosphatase SHP2 impact ligand binding specificity, enzyme activation, and downstream signaling. This paper includes a lot of rigorous biophysical and biochemical measurements of SHP2 mutants, high-throughput peptide display screens to profile SH2 domain specificity, detailed structural analysis using molecular dynamics simulations (in collaboration with Deepti Karandur at Vanderbilt), and cell signaling assays.
May 2023 - Neel was accepted as a full member of the Precision Oncology and Systems Biology Program at the Herbert Irving Comprehensive Cancer Center at Columbia University.
May 2023 - Congrats to Dr. Allyson Li on successfully defending her PhD thesis! Allyson's thesis is entitled "High-throughput profiling of sequence recognition by phosphotyrosine signaling proteins."
May 2023 - We welcome Zijing Wang from Barnard College as the next undergraduate researcher in the lab! Zijing was awarded funding from the Barnard Summer Research Institute. We also welcome Miles Gantcher, a chemistry undergraduate from Rice University, as a visiting researcher in the lab this summer!
May 2023 - Congratulations to Allyson Li for receiving Chemistry Department's Pegram Award, for meritorious achievements in the final year of her PhD, and for receiving the Departmental Service Award, for her numerous contributions to departmental affairs, student governance, and overall improvement of Columbia Chem!
May 2023 - Congrats to undergraduate Sarah Xi on her graduation from Columbia College, for receiving Chemistry departmental honors, and for being awarded the Thomas J. Katz prize for her outstanding achievements as a scholar and researcher!
May 2023 - We're looking hire a postdoctoral researcher to investigate mutational effects on phosphotyrosine signaling proteins using a range of biochemical, biophysical, and cell biological approaches. Check out the full job ad here.
May 2023 - Our group is delighted to receive several travel grants to attend The Protein Society Annual Symposium this year! Anne, Cassie, and Sarah received Diversity, Equity, and Inclusion Travel Awards, and Jason and Andrew received Finn Wold and Protein Science Young Investigator Travel Awards. We'll be out in full force at the meeting this July and look forward to showcasing lots of projects!
April 2023 - Congratulations to Madeleine Hum for receiving the Société de Chimie Industrielle summer fellowship from the Columbia Chemistry Department!
March 2023 - Congrats to Sarah Xi on receiving an NSF Graduate Research Fellowship! Sarah will activate this fellowship when she starts her PhD program after graduating from Columbia College.
March 2023 - We're excited to announce that the lab has received a Research Scholar Grant from the American Cancer Society to investigate how mutations in phosphotyrosine signaling proteins tune and rewire cancer signaling!
March 2023 - Our paper on a high-throughput method to profile tyrosine kinase and SH2 domain sequence recognition was just accepted to eLife as a Tools and Resources article. Congrats to Allyson Li and the whole peptide display subgroup!
March 2023 - Our paper on covalent ligands for tyrosine phosphatases was accepted at ChemBioChem and highlighted in the ChemBioTalents 2022/23 special collection! Congratulations to Suk ho Hong, Sarah Xi, and all of the other authors!
Feb. 2023 - Congrats to Sarah Xi on receiving the Euretta J. Kellett Fellowship, which will fund her study abroad at Cambridge University for one year after graduating from Columbia!
Jan. 2023 - Congrats to our postdoc Dr. Rashmi Voleti on her new job with Boston Consulting Group. We're sad to say farewell but excited for you to start the next stage of your career!
2022
Dec. 2022 - We are excited to share our recent paper in JACS, in collaboration with the Rovis lab here at Columbia Chemistry, entitled "Modular Synthesis of Unnatural Peptides via Rh(III)-Catalyzed Diastereoselective Three-Component Carboamidation Reaction." This paper describes a strategy where peptides bearing C-terminal dioxazalones and N-terminal acrylamides can be readily bridged with an aryl boronic acid to simultaneously ligate peptides and incorporate diverse unnatural amino acids at the juncture. Congrats to first author Chris Lamartina from the Rovis lab and Cassie Chartier from our group on this great collaborative project!
Nov. 2022 - Congrats to co-first authors Suk ho Hong and Sarah Xi on their preprint posted to ChemRxiv, entitled “Mapping the chemical space of active-site targeted covalent ligands for protein tyrosine phosphatases." In this paper, we explore the chemical parameters required for inhibition of tyrosine phosphatases by targeting the catalytic cysteine residue. Using an array of assays and a curated library of electrophilic fragment molecules, we identify previously unappreciated scaffolds compatible with phosphatase inhibition. Our experiments, coupled with sequence and structure analysis, also reveal structural features of tyrosine phosphatases that govern their very divergent levels of intrinsic activity and susceptibility to covalent inhibition.
Oct. 2022 - Congrats to Sarah on receiving the Outstanding Presentation in Chemical Biology Award for her presentation at the Gulf Coast Undergraduate Research Symposium!
Oct. 2022 - We are excited to welcome Oskar Salas, a biochemistry major at Columbia College, as our lab's newest undergraduate researcher!
Aug. 2022 - Congratulations to Dr. Suk ho Hong, the first graduate student from our lab to defend their PhD thesis!! Suk ho's thesis is entitled "Designing Active Site-Directed Covalent Probes for Tyrosine Phosphatases".
Aug. 2022 - Our peptide display subgroup, with first author Allyson Li, just posted their first preprint on bioRxiv, entitled "High-throughput profiling of sequence recognition by tyrosine kinases and SH2 domains using bacterial peptide display." This paper lays out a platform to rapidly screen the substrate and ligand specificities of tyrosine kinases and SH2 domains, by combining bacterial surface display of peptide libraries with deep sequencing. We show that different libraries yield different insights into kinase/SH2 function. We also show that the chemical diversity of these libraries can be expanded using Amber codon suppression, to test the effects of non-canonical and post-translationally modified amino acids on sequence recognition.
July 2022 - Congrats to Cassie for receiving an award from the ACS Graduate Student and Postdoctoral Scholars Recognition Program, for her Leadership in the Promotion of Diversity, Equity, Inclusion, and Respect!
May 2022 - Our first collaboration with Harmen Bussemaker's lab was published in Nature Biotechnology. The work was led by Tomas Rube and Chaitanya Rastogi from the Bussemaker group, with contributions by Allyson Li from our group. The paper describes a new biophysically-interpretable machine learning algorithm to model/predict protein-DNA affinities and tyrosine kinase substrate selectivity from deep sequencing data.
May 2022 - Congrats to Allyson Li on receiving the Chemistry Department's Arun Guthikonda Fellowship! This fellowship is awarded to a student in organic chemistry or biologically related science in recognition of that student's distinguished achievements and potential.
May 2022 - Congrats to Andrew Johns on receiving the Chemistry Department's Miller Teaching Award!
May 2022 - Check out lots of exciting talks from our lab in the coming months: Cassie will be giving at talk at the NYAS ChemBio Discussion Group Year-End Meeting, Suk ho is giving a talk at ACS MARM, and Allyson is giving a talk at The Protein Society Annual Meeting! Allyson and Suk ho both received travel awards from ACS and TPS to support their attendance!
May 2022 - Congrats to our lab's first undergrad, Alyssa Semmelman, on her graduation from Barnard College with a Bachelor's degree in biology!
May 2022 - Congrats to Andrew for completing his 2nd year defense!
April 2022 - Check out this preprint from Neel's postdoctoral work, in collaboration with his former labmate Helen Hobbs, on ancestral sequence reconstruction and deep mutational scanning of Syk-family tyrosine kinases. Lack of soluble expression of these kinases in bacteria has slowed down biochemical and biophysical studies. Ancestral sequence reconstruction led to the discovery of a bacterially-expressing Syk-family kinase with preserved specificity and allosteric regulation of human family members. This engineered protein enabled the development of a bacterial two-hybrid assay to rapidly analyze thousands of kinase domain mutants!
April 2022 - Congrats to Minhee for completing his 2nd year defense!
March 2022 - Madeleine and Sarah both received the undergraduate Guthikonda Summer Fellowship from Columbia Chemistry!
March 2022 - Congrats to Sarah Xi for being named a 2022 Goldwater Scholar!
Jan. 2022 - Check out this preprint from Neel's postdoctoral work (now in eLife), led by his former labmates Frank Hidalgo and Laura Nocka, on the interplay between stability and mutational sensitivity in the oncogenic signaling protein H-Ras. The paper combines deep mutational scanning in a bacterial two-hybrid system, mutational scans in mammalian cells, and measurements of Ras stability and dynamics to explain why certain gain-of-function mutations in Ras observed in vitro do not appear in cancers.
2021
Nov. 2021 - Congrats to Allyson for passing her 4th year original research proposal!
Oct. 2021 - Neel was named an RCSA Scialog Fellow and participated in the Chemical Machinery of the Cell meeting!
July 2021 - Check out this preprint from Neel's postdoctoral work (now in Protein Science), led by his former labmate Helen Hobbs, on divergent dynamics in the tandem SH2 domains of the closely-related B and T cell kinases Syk and ZAP-70. The paper combines X-ray crystallography, H/D exchange mass spectrometry, molecular dynamics simulations, and evolutionary analysis to pinpoint mechanisms of structural/functional divergence in these two proteins.
July 2021 - Congrats to Sarah for winning a poster award at the Protein Society's 35th annual symposium!
July 2021 - Check out our preprint, led by our collaborators in the Bussemaker Lab, on a new machine learning method to probe and design biomolecular interactions using data from selection and deep sequencing assays. As a proof of concept, Allyson combined this technique with our kinase specificity platform to profile Src kinase substrate recognition and design a Src super-substrate.
July 2021 - We are excited to welcome Madeleine Hum as our newest undergraduate researcher from Columbia College.
June 2021 - Cassie and Jason completed their second year defenses!
June 2021 - Congrats to Anne for being named a Lead Teaching Fellow through Columbia's Center for Teaching and Learning! ​
April 2021 - Congratulations to Sarah for receiving the Société de Chimie Industrielle summer fellowship from the Columbia Chemistry Department!​
March 2021 - Congratulations to Sarah on being accepted into the NSF Center for Sustainable Polymers summer undergraduate research program at the University of Chicago!​
March 2021 - Congratulations to Cassie for receiving the NSF Graduate Research Fellowship!
Feb. 2021 - Check out our new lab tour video, produced by Cassie and Suk ho!
Jan. 2021 - Dr. Rashmi Voleti joins from the University of Texas Southwestern Medical Center as our newest postdoctoral fellow.
2020
Dec. 2020 - Congrats to Suk ho for passing his 4th year original research proposal!
Dec. 2020 - Neel joins the ACS Chemical Biology Early Career Advisory Board.
Dec. 2020 - We had a blast at our first lab outreach event, a "virtual" visit to a 3rd grade class at Swasey Central School in NH for a lab tour, some fun demonstrations, and a deep conversation about what it means to be a scientist.
Oct. 2020 - We're excited to welcome two new graduate students, Minhee Lee and Andrew Johns, to the lab!
Oct. 2020 - Dr. Dejan Gagoski joins us from the University of Queensland, Australia, as a joint postdoc with Harmen Bussemaker's lab in the Biological Sciences department.
Sept. 2020 - We just moved into our newly-renovated home on the 4th floor of Havemeyer Hall!
July 2020 - We received our first NIH grant from NIGMS! This grant will fund our efforts to develop new biochemical and cell-based strategies to dissect tyrosine phosphatase interactions and regulation!
June 2020 - Congrats to Allyson and Anne for passing their 2nd year candidacy exams!
March 2020 - Check out Neel's book chapter with Adam Stevens on methods to identify and characterize split inteins, published in the Methods in Molecular Biology volume on Expressed Protein Ligation.
Jan. 2020 - We're excited to have our second undergrad, Sarah Xi, join the lab from Columbia College!
2019
Oct. 2019 - The lab grows! Cassie Chartier and Jason Jiang join us as the newest graduate students from the Chemistry program!
Oct. 2019 - Neel was featured in the RockEDU Scientists of New York blog, which showcases the personal side of local scientists.
Oct. 2019 - Check out Neel's recent paper from his postdoc work in collaboration with Wan-Lin Lo in the Weiss lab at USCF, just published in Nature Immunology. This paper shows how the T cell activation threshold can be tuned by altering phosphosite sequences using our knowledge of tyrosine kinase specificity.
Aug. 2019 - Anne van Vlimmeren joins us as the first graduate student in the Shah Lab from Columbia's Biological Sciences graduate program!
Aug. 2019 - Check out Suk ho and Neel's insight article in eLife commenting on a great paper by Liam Holt and co-workers on the evolution of MAP kinase activation and regulation.
June 2019 - We're sad to see John Varriano leave the lab after an an awesome 8-month run. John was instrumental in helping us get the lab off the ground, and we wish him the best of luck at Rutgers Medical School!
May 2019 - We're excited to welcome Alyssa Semmelman from Barnard College is the first undergrad in the Shah Lab!
April 2019 - Congrats to Suk ho on passing his second year candidacy exam!
2018
Dec. 2018 - Check out Neel's new review in Nature Structural & Molecular Biology on sequence-variation-based methods to study cell signaling proteins.
Dec. 2018 - Neel received a Lenfest Junior Faculty Development Award to support our work on specificity profiling!
Nov. 2018 - Allyson Li joins the lab as our second graduate student!
Oct. 2018 - John Varriano joins us from Hunter College as a research technician.
Sept. 2018 - The Shah Lab sets up shop! Excited to bring on Suk ho Hong as the first graduate student in the lab.
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