We are a group of biochemists, biologists and physicians in the Molecular Pharmacology Program at the Sloan Kettering Institute in New York City, USA. We carry out research in cancer biology, and our current work is focused on the phenomenon of cellular plasticity, as it relates both to the fundamental mechanisms of cancer pathogenesis and emerging rational therapies.

In particular, we are studying the biology of refractory leukemias and solid tumors, and we are interested in understanding the principles of disorganization of their genomes and proteomes, and determining the molecular mechanisms of response and adaptation of tumor cells to targeted therapies.

To answer these questions, we are developing new approaches, based on quantitative mass spectrometry and functional proteomics, to decipher the mechanisms of cancer cell signaling and develop new therapeutics.

Forward Proteomic Screens for Cancer Therapeutics and Macromolecular Delivery .

Using recently developed methods for quantitative proteomics and peptide barcoding (Egloff et al, Nature Methods 2019, PMID: 31113958), weve developed a new platform for high-throughput design and screening of macromolecular cell penetration and delivery reagents. This is a transformative technology that enables the generation of new classes of drugs to modulate specific protein-protein interactions, which weve recently applied for targeted leukemia therapy (Ramaswamy et al, Nature Communications 2018, PMID 29317678). Current efforts are focused on applying this technology for protein engineering and development of new peptide conjugates for cancer and gene therapy.

Single-cell Quantitative Mass Spectrometry and Proteogenomics for Cancer Mechanisms and Therapy .

Using improved methods for ultra-sensitive quantitative proteomics (Cifani & Kentsis, MCP 2017, PMID 28821601), weve developed an atlas of targeted mass spectrometry assays to profile biochemical signaling at the pathway scale in normal and cancer cells ( http://qcpa.mskcc.org ). Similarly, weve developed improved and scalable methods for comprehensive proteogenomics (Cifani et al, JPR 2018, PMID 30295032, https://github.com/kentsisresearchgroup/ProteomeGenerator2 ). Current efforts are focused on developing high-throughput and genome-scale methods to define oncogenic mechanisms in leukemia and other cancers, and identify targets for definitive therapy, including immunotherapies in particular. This work aims to define systems-level mechanisms of aberrant signaling in cancer cells, as well as fundamental cell biological processes of signaling adaptation, feedback and integration, and disorders of gene control leading to the expression of neomorphic antigens.

If you are a recent PhD graduate with interest in the above areas and experience with high-resolution mass spectrometry or protein engineering and chemistry, please contact Alex Kentsis at http://alexkentsis.net/ or kentsisresearchgroup+application@gmail.com

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