Sfeir Lab
Principal Investigator: Agnel Sfeir
Institution: Memorial Sloan Kettering Cancer Center (New York, NY)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
Project Summary Deregulation in DNA damage repair pathways can lead to genome instability, loss of genomic integrity, and ensuing chromosomal abnormalities, all of which are critical events driving the development of many cancers. A better understanding of DNA damage repair pathways and how these go awry in malignant transformation could form the basis for more efficacious therapeutic approaches for various cancers. Mammalian cells have evolved three major pathways to repair the highly toxic double-strand breaks (DSBs). Homologous Recombination (HR) is the preferred pathway, which fixes breaks without altering the original sequence. DSBs can also be repaired by Non-Homologous End-Joining (NHEJ) and Microhomology-Mediated End-Joining (MMEJ). MMEJ is the most mutagenic mode of DSB repair, mainly because of deletions and insertions that scar break sites following repair. In 2015, my lab attributed the source of the insertions to the activity of DNA polymerase theta (Pol coded by POLQ), a low-fidelity enzyme critical for MMEJ activity.Data from our group and others showed that tumor cells with defective HR highly depend on MMEJ to repair DSBs. These studies identified Pol as an attra…
Active NIH Awards
- 5R01CA294696-02: Investigating the role of Microhomology-Mediated End-Joining (MMEJ) in Mitosis and its impact on drug resistance (2026)
- 5R01AG085782-04: Investigating the impact and dynamic of mitochondrial common deletion in somatic cells (2026)
- 5R01GM150229-04: Investigating telomerase dynamics in live cells at a single-molecule level (2026)
- 5R01AG085782-03: Investigating the impact and dynamic of mitochondrial common deletion in somatic cells (2025)
- 1R01CA304441-01: Investigating Extrachromosomal DNA (ecDNA) Segregation and Repair in Cancer (2025)
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