the          lab

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.