Chan Lab
Principal Investigator: Edmond Chan
Institution: Columbia University (New York, NY)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
Abstract Synthetic lethality (SL) offers a promising approach to selectively target cancers by exploiting their genome alterations not found in normal cells. Indeed, various inhibitors of SL drug targets are approved by the Food and Drug Administration or in clinical trials, highlighting the potential of such a therapeutic approach. Building on our success identifying (Chan et al. Nature 2019)1 and undercovering the molecular mechanisms (van Wietmarschen et al. Nature 2020)45 of WRN helicase as a SL target, we sought to identify additional SL cancer targets. As detailed in our recent publication (Borck et al. Nature 2025)8, we discovered Pelota (PELO) – HBS1-like translational GTPase (HBS1L) ribosome rescue complex (PELO-HBS1L) as a novel synthetic lethal target for two distinct and large molecular subtypes of cancers: biallelic chromosome 9p21.3 deletion (9p21.3-/-) and microsatellite instability (MSI-H). These independent molecular subtypes represent large classes of lethal cancers with an urgent need for novel therapies. We showed that that 9p21.3-/- mutations and MSI-H-related mutations independently destabilized the Super Killer complex (SKIc), which typically promotes the deg…
Active NIH Awards
- 1R01CA300313-01A1: Advancing a novel synthetic lethal target by exploiting ribosomal stress in Ch9p21.3-deleted or MSI-H cancers (2026)
- 5K08CA256173-05: Advancing WRN as a synthetic lethal target for microsatellite unstable cancers (2025)
- 5K08CA256173-04: Advancing WRN as a synthetic lethal target for microsatellite unstable cancers (2024)
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