Human Oncology & Pathogenesis Program
The Samuel Bakhoum Lab
The Bakhoum lab focuses on understanding the role of chromosomal instability (CIN) in tumor evolution and progression. CIN is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. CIN results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. In addition to generating genomic heterogeneity that acts as a substrate for natural selection, Our team has identified numerous mechanisms by which CIN drives cancer progression. First, we found that CIN promotes inflammatory signaling by introducing genomic double-stranded DNA into the cytosol, engaging cytosolic DNA-sensing antiviral innate immune pathways. Instead of eliciting anti-tumor immunity, CIN-induced chronic inflammation promotes immune suppression and metastasis. In addition, we also CIN as an potent driver of epigenetic heterogeneity and reprogramming through chromosome encapsulation in micronuclei. These multipronged effects distinguish CIN as a central driver of tumor evolution and as a genomic source for the crosstalk between the tumor and its microenvironment. Our lab is interested in dissecting the mechanisms linking CIN and cancer progression and translating these discoveries into novel therapeutic strategies.
Li J, Hubisz MJ, Earlie EM, Duran MA, Hong C, Varela AA, Lettera E, Deyell M, Tavora B, Havel JJ, Phyu SM, Amin AD, Budre K, Kamiya E, Cavallo JA, Garris C, Powell SN, Reis-Filho J, Wen H, Bettigole S, Khan AJ, Izar B, Parkes EE, Laughney AM*, Bakhoum SF* (2023) Cancer cell non-autonomous tumor progression from chromosomal instability. Nature, 620, 1080-1088. PMID: 37612508
Agustinus AS, Al-Rawi D, Dameracharla B, Raviram R, Jones BS, 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 DA, Bakhoum MF, Koche RP, Sidoli S, Bafna V, David Y*, Bakhoum SF* (2023) Epigenetic dysregulation from chromosomal transit in micronuclei. Nature, 619, 176-183. PMID: 37286593
Li J, Duran MA, Dhanota N, Chatila WK, Bettigole SE, Kwon J, Sriram RK, Humphries MP, Salto-Tellez M, James JA, Hanna MG, Melms JC, Vallabhaneni S, Litchfield K, Usaite I, Biswas D, Bareja R, Li HW, Martin ML, Dorsaint P, Cavallo JA, Li P, Pauli C, Gottesdiener L, DiPardo BJ, Hollmann TJ, Merghoub T, Wen HY, Reis-Filho JS, Riaz N, Su SM, Kalbasi A, Vasan N, Powell SN, Wolchok JD, Elemento O, Swanton C, Shoushtari AN, Parkes EE, Izar B, Bakhoum SF (2021) Metastasis and immune evasion from extracellular cGAMP hydrolysis. Cancer Discovery, 11, 1212-1227. PMID: 33372007
Samuel Bakhoum, MD, PhD
Assistant Member, Human Oncology and Pathogenesis Program; Assistant Attending, Department of Radiation Oncology
- Physician-scientist Samuel Bakhoum studies the role of chromosomal instability in tumor evolution and metastasis.
- MD, Dartmouth Medical School
- PhD, Dartmouth College
- Mark Foundation Emerging Leader Award (2023-2026)
- BioInnovation Institute & Science Magazine Prize (Finalist) (2023)
- 20 Under 40 Next Generation of Biotech Leaders by Endpoint News (2022)
- Josie Robertson Investigator (2018-2023)
- AAAS Martin and Rose Wachtel Cancer Research Award (Honorable mention)
- NIH Director’s Independence Award (2018-2023)
- Blavatnik Regional Award for Young Scientists (Finalist) (2018)
- Tri-Institutional Breakout Prize (2018)
- Burroughs Wellcome Fund Career Award for Medical Scientists (2018)
- NextGen Stars, American Association for Cancer Research (AACR) (2018)
- Breast Cancer Breakthrough Award, Department of Defense (2016)
- ASCI/AAP Outstanding Young Investigator Award (2011)
- Norton B. Gilula Award, the American Society for Cell Biology (2008)
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Doctors and faculty members often work with pharmaceutical, device, biotechnology, and life sciences companies, and other organizations outside of MSK, to find safe and effective cancer treatments, to improve patient care, and to educate the health care community.
MSK requires doctors and faculty members to report (“disclose”) the relationships and financial interests they have with external entities. As a commitment to transparency with our community, we make that information available to the public.
Samuel Bakhoum discloses the following relationships and financial interests:
Equity; Professional Services and Activities
Volastra Therapeutics Inc.
Equity; Fiduciary Role / Position; Intellectual Property Rights; Professional Services and Activities
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