Walensky Lab
Principal Investigator: Loren David Walensky
Institution: Dana-Farber Cancer Institute (Boston, MA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: ✅ Accepting PhD Students ✅ Hiring Postdocs
Research Focus
PROJECT SUMMARY/ABSTRACT BCL-2 proteins participate in a dynamic interaction network that determines whether a cell will live or die. Deregulation of this essential signaling pathway underlies the pathogenesis of human cancer and resistance to treatment. The goal of this R35 research program is to elucidate the fundamental protein interaction mechanisms that drive the apoptotic program and harness these insights to develop next-generation cancer treatments. Over the last five years of R35 support, we applied novel chemical tools and a host of analytical technologies to achieve mechanistic discoveries that revealed new druggable binding sites and compounds to target them. We found that covalent modification of distinct cysteines in pro-apoptotic BAX and anti-apoptotic MCL-1 and BFL-1 differentially regulate their apoptotic functions. Our pursuit of covalent ligands that mimic these post-translational modifications are yielding prototype BAX activators and MCL-1 and BFL-1 inhibitors for cancer therapy. Deciphering how BAX and BAK are directly activated, and the conformational mechanisms that underlie their conversion from latent monomers into toxic mitochondrial oligomers, has also b…
Active NIH Awards
- 5R35CA197583-13: Dissecting and Targeting Deregulated Mitochondrial Apoptosis in Human Cancer (2026)
- 5R35CA197583-12: Dissecting and Targeting Deregulated Mitochondrial Apoptosis in Human Cancer (2025)
- 5R35CA197583-11: Dissecting and Targeting Deregulated Mitochondrial Apoptosis in Human Cancer (2024)
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