Benjamin Greenbaum, PhD

Associate Attending, Computational Oncologist
Epidemiology & Biostatistics
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Benjamin Greenbaum, PhD

Associate Attending, Computational Oncologist
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Benjamin Greenbaum

Office Phone

646-608-7667

Email

GreenbaB@mskcc.org

URL

View Benjamin Greenbaum's Lab

Education

Columbia University

Dr. Greenbaum’s main research interests have long centered around the fundamental question of self vs non-self discrimination: How does the immune system recognize and target particular molecular patterns and sequences as ‘foreign’, and how does this affect the evolution of tumors and viruses? As the director of Computational Immuno-Oncology within the Computational Oncology Service, Dr. Greenbaum combines statistical physics and information theory with evolutionary biology. After a PhD in theoretical physics from Columbia University he focused on the effect of the innate immune system on viral evolution: his models predicted how the 1918 influenza virus evolved after the pandemic and continued to be cited during Covid-19. His next step took him from virally transcribed RNA to viral mimics: RNA produced from genomic repeat elements in cancer cells. He applied methods from statistical physics to quantify how the immune system recognizes these aberrantly transcribed self-RNAs. Dr. Greenbaum developed the first models to quantify this ‘viral mimicry’, molecular patterns reminiscent of pathogens that can activate the innate immune system. Within the last few years Dr. Greenbaum’s group and his collaborators also created models to predict the role of neoantigens in tumor evolution, and they established the concept of ‘neoantigen quality’ to assess the likelihood that a neoantigen will induce an immune response. His team discovered an immune tradeoff in cancer evolution: oncogenic mutations with lower fitness present poorly to the immune system, while mutations with high fitness generate potent neoantigens. Dr. Greenbaum’s work is supported by various federal and philanthropic grants and awards and has contributed to several clinical trials, including a phase II trial to test an inhibitor of repeat elements in colorectal cancer and a phase I trial for an mRNA vaccine against neoantigens in pancreatic cancer.

Publications

  1. Rojas LA, Sethna Z, Soares KC, Olcese C, Pang N, Patterson E, Lihm J, Ceglia N, Guasp P, Chu A, Yu R, Chandra AK, Waters T, Ruan J, Amisaki M, Zebboudj A, Odgerel Z, Payne G, Derhovanessian E, Müller F, Rhee I, Yadav M, Dobrin A, Sadelain M, Łuksza M, Cohen N, Tang L, Basturk O, Gönen M, Katz S, Do RK, Epstein AS, Momtaz P, Park W, Sugarman R, Varghese AM, Won E, Desai A, Wei AC, D’Angelica MI, Kingham TP, Mellman I, Merghoub T, Wolchok JD, Sahin U, Türeci Ö, Greenbaum BD*, Jarnagin WR, Drebin J, O’Reilly EM, Balachandran VP*. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 2023 Jun;618(7963):144-150. PMCID: PMC10171177.
  2. Hoyos D, Zappasodi R, Schulze I, Sethna Z, de Andrade KC, Bajorin DF, Bandlamudi C, Callahan MK, Funt SA, Hadrup SR, Holm JS, Rosenberg JE, Shah SP, Vázquez-García I, Weigelt B, Wu M, Zamarin D, Campitelli LF, Osborne EJ, Klinger M, Robins HS, Khincha PP, Savage SA, Balachandran VP, Wolchok JD, Hellmann MD, Merghoub T, Levine AJ, Łuksza M, Greenbaum BD*. Fundamental immune-oncogenicity trade-offs define driver fitness. Nature. 2022 Jun;606(7912):172–179. PMCID: PMC9159948
  3. Łuksza M, Sethna ZM, Rojas LA, Lihm J, Bravi B, Elhanati Y, Soares K, Amisaki M, Dobrin A, Hoyos D, Guasp P, Zebboudj A, Yu R, Chandra AK, Waters T, Odgerel Z, Leung J, Kappagantula R, Makohon-Moore A, Johns A, Gill A, Gigoux M, Wolchok J, Merghoub T, Sadelain M, Patterson E, Monasson R, Mora T, Walczak AM, Cocco S, Iacobuzio-Donahue C, Greenbaum BD*, Balachandran VP*. Neoantigen quality predicts immunoediting in survivors of pancreatic cancer. Nature. 2022 Jun;606(7913):389–395. PMID: 35589842
  4. Lyudovyk O, Kim JY, Qualls D, Hwee MA, Lin YH, Boutemine SR, Elhanati Y, Solovyov A, Douglas M, Chen E, Babady NE, Ramanathan L, Vedantam P, Bandlamudi C, Gouma S, Wong P, Hensley SE, Greenbaum B*, Huang AC, Vardhana SA*. Impaired humoral immunity is associated with prolonged COVID-19 despite robust CD8 T cell responses. Cancer Cell. 2022 Jul 11;40(7):738-753.e5. doi: 10.1016/j.ccell.2022.05.013. Epub 2022 May 30. PMID: 35679859; PMCID: PMC9149241. 
  5. Lee CY, Shah MK, Hoyos D, Solovyov A, Douglas M, Taur Y, Maslak P, Babady NE, Greenbaum BD, Kamboj M, Vardhana SA. Prolonged SARS-CoV-2 infection in patients with lymphoid malignancies. Cancer Discov. American Association for Cancer Research (AACR); 2022 Jan 1;12(1):62–73. PMCID: PMC8758535
  6. Porter RL, Sun S, Flores MN, Berzolla E, You E, Phillips IE, Kc N, Desai N, Tai EC, Szabolcs A, Lang ER, Pankaj A, Raabe MJ, Thapar V, Xu KH, Nieman LT, Rabe DC, Kolin DL, Stover EH, Pepin D, Stott SL, Deshpande V, Liu JF, Solovyov A, Matulonis UA, Greenbaum BD*, Ting DT*. Satellite repeat RNA expression in epithelial ovarian cancer associates with a tumor-immunosuppressive phenotype. J Clin Invest. 2022 Aug 15;132(16). doi.org/10.1172/JCI155931 PMCID: PMC9374379
  7. Rajurkar M, Parikh AR, Solovyov A, You E, Kulkarni AS, Chu C, Xu KH, Jaicks C, Taylor MS, Wu C, Alexander KA, Good CR, Szabolcs A, Gerstberger S, Tran AV, Xu N, Ebright RY, Van Seventer EE, Vo KD, Tai EC, Lu C, Joseph-Chazan J, Raabe MJ, Nieman LT, Desai N, Arora KS, Ligorio M, Thapar V, Cohen L, Garden PM, Senussi Y, Zheng H, Allen JN, Blaszkowsky LS, Clark JW, Goyal L, Wo JY, Ryan DP, Corcoran RB, Deshpande V, Rivera MN, Aryee MJ, Hong TS, Berger SL, Walt DR, Burns KH, Park PJ, Greenbaum BD*, Ting DT*. Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer. Cancer Discov. 2022 Jun 2;12(6):1462–1481. PMCID: PMC9167735
  8. Hoyos D, Greenbaum BD*. Perfecting antigen prediction. J Exp Med. 2022 Sep 5;219(9). doi.org/10.1084/jem.20220846 PMCID: PMC9386507
  9. Hoyos D, Greenbaum BD, Levine AJ. The genotypes and phenotypes of missense mutations in the proline domain of the p53 protein. Cell Death Differ. 2022 May;29(5):938–945. PMCID: PMC9090814
  10. Bravi B, Balachandran VP, Greenbaum BD, Walczak AM, Mora T, Monasson R, Cocco S. Probing T-cell response by sequence-based probabilistic modeling. PLoS Comput Biol. 2021 Sep;17(9):e1009297. PMCID: PMC8476001
  11. Roudko V, Cimen Bozkus C, Greenbaum BD, Lucas A, Samstein R, Bhardwaj N. Lynch Syndrome and MSI-H Cancers: From Mechanisms to “Off-The-Shelf” Cancer Vaccines. Front Immunol. 2021 Sep 24;12:757804. doi: 10.3389/fimmu.2021.757804. PMID: 34630437; PMCID: PMC8498209.
  12. Hoyos D and Greenbaum BD Research Briefing: Tumor driver mutations compromise between cancer growth and immune response doi.org/10.1038/d41586-022-01138-8 (2022)
  13. Di Gioacchino A, Šulc P, Komarova AV, Greenbaum BD, Monasson R, Cocco S. The Heterogeneous Landscape and Early Evolution of Pathogen-Associated CpG Dinucleotides in SARS-CoV-2. Mol Biol Evol. 2021;38(6):2428-45.
  14. Solovyov A, Vabret N, …, Greenbaum BD*. Global cancer transcriptome quantifies repeat element polarization between immunotherapy responsive and T cell suppressive classes. Cell Reports 23:512-521 (2018).
  15. Łuksza M, Riaz N, …, Greenbaum BD. A neoantigen fitness model predicts tumor response to checkpoint blockade immunotherapy. Nature 551:517-520 (2017).
  16. Balachandran VP, Łuksza M, …, Greenbaum BD, et al. Neoantigen quality and an immunogenic hotspot define long term pancreatic cancer survivors. Nature 551:512-516 (2017).
  17. Tanne A, Muniz LR, …, Greenbaum BD*. Distinguishing the immunostimulatory properties of noncoding RNAs expressed in cancer cells. Proceedings of the National Academy of Sciences 112:15154-15159 (2015).
  18. Greenbaum BD, Levine AJ, Bhanot G, Rabadan R. Patterns of evolution and host gene mimicry in influenza and other RNA viruses. PLoS Pathogens 4:e1000079 (2008).

[* denotes Corresponding author]

Disclosures

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.

Benjamin Greenbaum discloses the following relationships and financial interests:

  • DarwinHealth Inc.
    Professional Services and Activities
  • Icahn School of Medicine at Mount Sinai
    Intellectual Property Rights
  • Merck Sharp & Dohme
    Professional Services and Activities
  • Rome Therapeutics
    Equity; Intellectual Property Rights; Professional Services and Activities
  • Shennon Biotechnologies Inc.
    Equity
  • Sibyl Analytics LLC
    Equity; Fiduciary Role / Position; Professional Services and Activities (Uncompensated)
  • Zonklers, LLC
    Professional Services and Activities (Uncompensated)

The information published here is a complement to other publicly reported data and is for a specific annual disclosure period. There may be differences between information on this and other public sites as a result of different reporting periods and/or the various ways relationships and financial interests are categorized by organizations that publish such data.

This page and data include information for a specific MSK annual disclosure period (January 1, 2023 through disclosure submission in spring 2024). This data reflects interests that may or may not still exist. This data is updated annually.

Learn more about MSK’s COI policies here. For questions regarding MSK’s COI-related policies and procedures, email MSK’s Compliance Office at ecoi@mskcc.org.


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