Shared Resource Spotlight: Proteomics and Macromolecular Crystallography

May 25, 2020

The Proteomics and Macromolecular Crystallography Shared Resource (PMCSR) provides researchers cutting-edge proteomic and structural biology technologies and analysis. Co-directed by Farhad Forouhar, PhD, and Rajesh Soni, PhD, the PMCSR combines mass spectrometry-based proteomic technologies, which are essential tools for identification of molecular mechanisms, druggable targets, and novel biomarkers in cancer, and crystallography, the primary technique for investigating crystal structures of macromolecules (proteins, DNA, and RNA) that are implicated in cancer and other diseases.

The PMCSR at the Herbert Irving Comprehensive Cancer Center (HICCC) supports both discovery-based and targeted proteomic analysis. The facility, located in the Lasker Biomedical Research Building, provides cancer researchers access to state-of-the-art mass spectrometers and software for qualitative (e.g. protein identification), quantitative (e.g. relative quantification), and post-translational modification (PTM) analyses. The services include i) mass determination of purified proteins/peptides, ii) identification of purified protein complexes, iii) site-targeted PTM mapping on purified proteins, targeted MRM quantification, iv) global proteome analysis, sub-proteome isolation, and identification, and v) large-scale PTM characterization.

This shared resource gives researchers access to crystallographic services for critical insight into function of a macromolecule and how it could be inhibited by structure-based drug design methodology. The core has helped advance cancer research on multiple fronts, including work with HICCC member Adolfo Ferrando, MD, PhD, that looked at the structure and mechanisms of NT5C2 mutations as a crucial driver of resistance in relapsed lymphoblastic leukemia. This work appeared as the cover paper in Cancer Cell in 2018. The PMCSR has also been collaborating with three groups at Columbia University on drug design for SARS-CoV-2 3CL main protease and nucleocapsid N protein.

For more details about the PMCSR, visit the HICCC Shared Resources page.