Daniel Bachovchin

Daniel Bachovchin is Professor of Molecular Pharmacology at Memorial Sloan Kettering Cancer Center (MSKCC), where he leads a research laboratory focused on inflammasome biology and chemical immunology. His work bridges chemical biology and innate immunity, with primary affiliations through the Tri-Institutional Training Program in Chemical Biology and collaborations across MSKCC's molecular pharmacology research division.

Research interests center on the molecular mechanisms of NLRP1 and CARD8 inflammasome activation, particularly how proteases like DPP8/9 regulate these pathways. His laboratory employs chemical biology approaches to develop selective inhibitors and probes, revealing how cytosolic peptide accumulation, redox stress, and proteolytic events trigger pyroptosis. Recent work demonstrates CARD8's role as a sensor for proteasome dysfunction and NLRP1's response to reductive stress.

Analysis of recent publications (2021-2024) shows a clear trajectory from structural characterization of inflammasome components toward therapeutic applications. Key themes include:

• Elucidation of NLRP1/CARD8 activation by redox changes and proteolytic events
• Development of M24B aminopeptidase inhibitors as selective inflammasome activators
• Discovery of DPP9's dual roles in inflammasome repression through both enzymatic and scaffolding functions

The Bachovchin Lab actively trains graduate students from the Tri-Institutional Training Program in Chemical Biology, Gerstner Sloan Kettering Graduate Program, and Weill Cornell Medical College Pharmacology program. Postdoctoral fellows receive competitive compensation through MSKCC's subsidized housing program while investigating innate immunity mechanisms. Current research leverages chemical tools to explore inflammasome biology in cancer contexts, particularly examining how immune activation pathways could be harnessed for leukemia treatment as suggested by earlier work on DPP8/9 inhibitors.

Experimental approaches combine high-throughput screening, structural biology, and chemical proteomics to dissect inflammasome regulation. The laboratory maintains strong collaborative ties with structural biologists (e.g., Hao Wu's lab) and microbiome researchers, reflecting the interdisciplinary nature of modern immunology research.