Epidemiology & Biostatistics

The Benjamin Greenbaum Lab

Research

Benjamin Greenbaum
Benjamin Greenbaum, PhD


Associate Professor

A main goal in the Greenbaum lab is to quantify how the immune system is activated and how it impacts tumor evolution. A particular focus in the lab is the role of repetitive elements in the genome, which mimic viral features and, just like viruses, evolve to escape immune surveillance. Dr. Greenbaum developed the first models to quantify this ‘viral mimicry’, molecular patterns reminiscent of pathogens that can activate the innate immune system (Greenbaum et al. PNAS 2014; Solovyov et al. Cell Reports 2018). These data recently contributed to a phase II clinical trial of 3TC, a reverse transcriptase inhibitor that prevented the activation of retrotransposons in patients with metastatic colorectal cancer and showed clinical benefits in 9 of 32 patients (Rajurkar et al. Cancer Discovery 2022). Viral mimics play an underappreciated role in tumor evolution and Dr. Greenbaum’s work reveals new vulnerabilities to be exploited.  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 (Luksza et al. Nature, 2022). Models that contributed to motivating a recent phase I clinical trial (Rojas et al. Nature 2023). 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 (Hoyos et al. Nature 2022). The goal of Immuno-Oncology is to act as a bridge between Computational Oncology and other investigators and clinicians in immuno-oncology at MSK, with the ultimate aim to use the power of the immune system to fight cancer. 

Research Projects

The Benjamin Greenbaum lab group

Publications Highlights

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. doi: 10.1038/s41586-022-04735-9. Epub 2022 May 19. PMID: 35589842; PMCID: PMC9177421.

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 mutation fitness. Nature. 2022 Jun;606(7912):172-179. doi: 10.1038/s41586-022-04696-z. Epub 2022 May 11. Erratum in: Nature. 2022 May 31;: PMID: 35545680; PMCID: PMC9159948.

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. doi: 10.1158/2159-8290.CD-21-1117. PMID: 35320348; PMCID: PMC9167735.

Roudko V*, Bozkus CC*, Orfanelli T, McClain CB, Carr C, O’Donnell T, Chakraborty L, Samstein R, Huang KL, Blank SV, Greenbaum B*, Bhardwaj N*. Shared Immunogenic Poly-Epitope Frameshift Mutations in Microsatellite Unstable Tumors. Cell 183:1634-1649 (2020).

Nogalski MT, Solovyov A, Kulkarni AS, Desai N, Oberstein A, Levine AJ, Ting DT, Shenk T, Greenbaum BD. A tumor-specific endogenous repetitive element is induced by herpesviruses. Nat Commun. 10:90 (2019).

Solovyov A*, Vabret N*, Arora KS, Snyder A, Funt SA, Bajorin DF, Rosenberg JE, Bhardwaj N, Ting DT*, Greenbaum BD*. Global cancer transcriptome quantifies repeat element polarization between immunotherapy responsive and T cell suppressive classes. Cell Reports 23:512-521 (2018).

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People

Benjamin Greenbaum

Benjamin Greenbaum, PhD



Associate Professor

  • The Greenbaum lab utilizes techniques from statistical physics, information theory, and evolutionary biology to better understand the role of self/non-self discrimination in tumor evolution, model response to immunotherapies, and quantify drivers of virus and cancer evolution.
  • PhD in theoretical physics, Columbia University
[email protected]
Email Address

Members

Samuel Ahuno
Samuel Ahuno

Graduate Research Assistant

Yuval Elhanati
Yuval Elhanati

Senior Research Scientist

David Hoyos
David Hoyos

Graduate Student

Hao Li
Hao Li

Bioinformatics Software Engineer II

Jayon Lihm
Jayon Lihm

Senior Computational Biologist II

Olga Lyudovyk
Olga Lyudovyk

Bioinformatics Technician

Stephen Martis
Stephen Martis

Postdoctoral Research Scholar

Martina Milighetti

Research Fellow

Jahan Rahman
Jahan Rahman

Computational Biologist II

Zachary Sethna, PhD
Zachary Sethna

Research Associate

Alexander Solovyov
Alexander Solovyov

Senior Research Scientist

Siyu Sun
Siyu Sun

Postdoctoral Research Scholar

Estelle (Ning) Yao

Graduate Research Assistant

Beatrice Zhang

Graduate Research Assistant

Lab Alumni
Alex Chu
Alex Chu

Computational Biologist I

Rami Vanguri
Rami Vanguri

Senior Computational Biologist II

Lab Affiliations

Achievements

  • Invited Professor, Statistical Physics, École Normale Supérieure (2022)
  • The Mark Foundation for Cancer Research ASPIRE Award (2021)
  • Pancreatic Cancer Collective Phillip A. Sharp Challenge Award (2021)
  • Pershing Square Foundation COVID-19 Award (2020)
  • NextGen Innovator, HemOnc Today (2019)
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  • Pershing Square Sohn Prize for Young Investigators in Cancer Research (2018)
  • Mark Foundation Investigator Award (2018)
  • Phillip A. Sharp Award for Innovation in Collaboration, Stand Up to Cancer (2016)

Open Positions

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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 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, 2022 through disclosure submission in spring 2023). 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 [email protected].


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