Michael Kong, FCLC 2026

Major: Natural Sciences (Cell & Molecular Biology)

Bio: Michael is a junior at Fordham College Lincoln Center majoring in Natural Sciences with focus on Cell and Molecular Biology. He is passionate about improving healthcare through science. He plans to pursue a career in medicine and research, leveraging the latest scientific findings to optimize cancer therapies. In his spare time, Michael enjoys hiking with his two German short-haired pointers, Toby and Luna.

Title of Research: Investigating how human cells cope with loss of BRCA2

Mentor: Jason Morris, Ph.D., Natural Sciences

Abstract: The ability of cells to detect and properly repair DNA lesions is essential for maintaining genome stability and preventing tumorigenesis. BRCA2 has a pivotal role in homologous recombination (HR), an error-free DNA repair mechanism. Indeed, acute loss of BRCA2 leads to replication stress that impacts all subsequent cell cycle phases: G2 with ssDNA and DSB accumulation; DNA synthesis during mitosis, chromosome missegregation and micronuclei, and G1 53BP1 nuclear body formation. Consequently, cells undergo senescence and apoptosis.

However, a percentage of breast, ovarian, pancreatic and prostate cancers show BRCA2 loss, indicating that tumor cells can cope with the absence of BRCA2.

To address this conundrum, I have isolated BRCA2-deficient survivor clones in non-transformed human epithelial cells (RPE1 cell lines). Survivors are slow growing and maintain HR defects and PARP inhibitor sensitivity. Accumulation of DNA damage (P-H2AX) is typically detected, especially after DNA replication, with associated genome instability (micronuclei).

Interestingly, compared to cells with acutely depleted BRCA2, some survivors display less post-replicative DNA damage. Survivors have reduced global DNA synthesis measured by EdU incorporation, suggesting that slowing down replication may help reduce DNA damage and genome instability. Moreover, all survivors are defective in activating the DNA damage checkpoint kinase CHK2 and some show reduced RPA foci. Altogether, my data suggest that survivors have developed a few strategies to overcome BRCA2 loss. Future work will focus on understanding how DNA replication and CHK2 signalling are regulated in these cells.