Examining the Link between Chromosomal Instability and Epigenetic Reprogramming in Cancer

2023 Emerging Leader Award

Samuel Bakhoum, MD, PhD, Memorial Sloan Kettering Cancer Center

Samuel Bakhoum, MD, PhD

Chromosomal instability, or the ability of cancer cells to continuously shuffle their chromosomes, has been associated the ability of cancer cells to spread and resist therapies. Dr. Bakhoum’s team has uncovered that this is in part due to the ability of chromosomal instability to alter the epigenome, thereby allowing cancer cells to sample a variety of genes that promote cancer survival and resistance. Here, they will use nascent transcription assays, single cell genomics, super-resolution microscopy, and human tumor samples to build on these findings. This work will broaden our understanding of how chromosomal instability drives tumor heterogeneity and provide avenues for therapeutic interventions in these tumors.

Dr. Bakhoum is a physician-scientist and group leader in the Human Oncology and Pathogenesis Program and an attending physician in the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center. His laboratory focuses on understanding the causes and consequences of chromosomal instability in cancer, and uncovering the link between chromosomal instability and epigenetic dysregulation, two hallmarks of advanced and metastatic cancers.

published research

Agustinus AS, Al-Rawi D, Dameracharla B, Raviram R, Jones BSCL, Stransky S, Scipioni L, Luebeck J, Di Bona M, Norkunaite D, Myers RM, Duran M, Choi S, Weigelt B, Yomtoubian S, McPherson A, Toufektchan E, Keuper K, Mischel PS, Mittal V, Shah SP, Maciejowski J, Storchova Z, Gratton E, Ly P, Landau D, Bakhoum MF, Koche RP, Sidoli S, Bafna V, David Y, Bakhoum SF. Epigenetic dysregulation from chromosomal transit in micronuclei. Nature. 2023.

Toufektchan E, Dananberg A, Striepen J, Hickling JH, Shim A, Chen Y, Nichols A, Duran Paez MA, Mohr L, Bakhoum SF, Maciejowski J. Intratumoral TREX1 induction promotes immune evasion by limiting type I interferon. Cancer Immunol Res. 2024.