Nassour Lab
Principal Investigator: Joe Nassour
Institution: University of Colorado Anschutz (Aurora, CO)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: ✅ Hiring Postdocs
Research Focus
PROJECT SUMMARY/ABSTRACT Telomeres are specialized nucleoprotein complexes that protect chromosome ends from being misidentified as DNA double-strand breaks, thereby preventing catastrophic genomic instability. This protective function relies on Shelterin, a six-member multiprotein complex (TRF1, TRF2, POT1, RAP1, TIN2, TPP1) that coats telomeric DNA. Although Shelterin can assemble into subcomplexes with varying compositions, how these distinct configurations prevent inappropriate DNA repair at chromosome ends remains poorly understood. In this R35 proposal, we advance a novel model of telomere end protection. We hypothesize that critically short, dysfunctional telomeres adopt an altered molecular architecture—marked by changes in Shelterin abundance, stoichiometry, and spatial distribution—that enables the microhomology-mediated end joining (MMEJ) repair pathway. We propose that this aberrant state gives rise to a unique signature of sister chromatid fusion and complex genomic rearrangements that remain incompletely understood. To investigate this, we have developed in vitro systems of spontaneous telomere dysfunction in isogenic normal human fibroblasts and epithelial cells unde…
Active NIH Awards
- 1R35GM162843-01: Chromatin Landscape and DNA Repair Dynamics at Dysfunctional Telomeres (2026)
- 1R21AG100775-01: Lysosome-Golgi Contact Sites as Regulators of Senescence-Associated Inflammation (2026)
- 5R00CA252447-05: The role of autophagy in the escape from replicative crisis and tumorigenesis (2025)
- 5R00CA252447-04: The role of autophagy in the escape from replicative crisis and tumorigenesis (2024)
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