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Benjamin Greenbaum

  • ASSISTANT PROFESSOR Medicine, Hematology and Medical Oncology
  • ASSISTANT PROFESSOR Pathology
  • ASSISTANT PROFESSOR (PENDING) Oncological Sciences
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Education

  • Ph.D., Columbia University

Biography

    I am a quantitative biologist working at the intersection of cancer research, evolution, immunology, and virology. Our lab uses tools from theoretical physics, mathematics and computer science to better understand host-virus interactions and the role they play in cancers. Previously, we showed how single-stranded RNA viruses evolve to mimic the genomic environment of their hosts. We found that the original 1918 influenza lineage altered its genome to mimic dinucleotide composition features of the human genome, and found that such host gene mimicry is a generic feature of such viruses. Importantly, we hypothesized that the innate immune system enforces this by recognizing such motifs in viral genomes and worked closely with Professor Nina Bhardwaj, currently a colleague at the Icahn School of Medicine at Mount Sinai, to validate our hypothesis.

    Such features can be used to infer the nature of host innate immune forces on viruses – with an emphasis on distinguishing highly pathogenic viruses, such as avian influenza, from other circulating strains. Using tools from statistical physics and information theory, we further quantified how viruses evolve to avoid using certain RNA motifs independently of protein evolution, patterns in viral reassortment in segmented viruses, and genome organization and diversity in influenza, HIV and HSV. Our goal is to translate these results into experimentally testable hypotheses and clinically meaningful outcomes.

    The significance of the mechanisms driving viral evolution and host-virus interactions in cancer has recently become fully appreciated. As a result we are applying our approaches to problems in cancer immunology. We are working to quantify the role of the immune system in several cancers, the interaction of host genomic material with immune receptors, and the role of viruses in cancers. Recently we demonstrated how a set of non-coding RNA emanating from genomic "dark matter" repetitive regions has properties of pathogenic RNA, and therefore may be immunogenic in the tumor microenvironemnt. We worked with the Bhardwaj laboratory to validate this hypothesis. In addition to using our approaches to shed light on these scientific issues, we are working to translate them into clinically impactful results in areas such as immunotherapy. At the same time we continue to develop novel quantitative approaches to a variety of problems in host and viral genome evolution.

Publications

Poon LL, Song T, Rosenfeld R, Lin X, Rogers MB, Zhou B, Sebra R, Halpin RA, Guan Y, Twaddle A, DePasse JV, Stockwell TB, Wentworth DE, Holmes EC, Greenbaum B, Peiris JS, Cowling BJ, Ghedin E. Quantifying influenza virus diversity and transmission in humans. Nature genetics 2016 Feb; 48(2).

Tanne A, Muniz LR, Puzio-Kuter A, Leonova KI, Gudkov AV, Ting DT, Monasson R, Cocco S, Levine AJ, Bhardwaj N, Greenbaum BD. Distinguishing the immunostimulatory properties of noncoding RNAs expressed in cancer cells. Proceedings of the National Academy of Sciences of the United States of America 2015 Nov;.

Fernandez MV, Miller E, Krammer F, Gopal R, Greenbaum BD, Bhardwaj N. Ion efflux and influenza infection trigger NLRP3 inflammasome signaling in human dendritic cells. Journal of leukocyte biology 2015 Nov;.

Greenbaum BD, Ghedin E. Viral evolution: beyond drift and shift. Current opinion in microbiology 2015 Jul 26.

Bonfante G, El-Aqqad M, Greenbaum B, Hoyrup M. Immune Systems in Computer Virology. In: Evolving Computability. Springer International Publishing; pp127-136.

Rogers MB, Song T, Sebra R, Greenbaum BD, Hamelin ME, Fitch A, Twaddle A, Cui L, Holmes EC, Boivin G, Ghedin E. Intrahost dynamics of antiviral resistance in influenza a virus reflect complex patterns of segment linkage, reassortment, and natural selection. mBio 2015; 6(2).

Greenbaum BD, Kumar P, Libchaber A. Using first passage statistics to extract environmentally dependent amino acid correlations. PloS one 2014; 9(7).

Wagh K, Bhatia A, Greenbaum BD, Bhanot G. Bird to human transmission biases and vaccine escape mutants in H5N1 infections. PloS one 2014; 9(7).

Greenbaum BD, Cocco S, Levine AJ, Monasson R. Quantitative theory of entropic forces acting on constrained nucleotide sequences applied to viruses. Proceedings of the National Academy of Sciences of the United States of America 2014 Apr; 111(13).

Szpara ML, Gatherer D, Ochoa A, Greenbaum B, Dolan A, Bowden RJ, Enquist LW, Legendre M, Davison AJ. Evolution and diversity in human herpes simplex virus genomes. Journal of virology 2014 Jan; 88(2).

Chin AW, Greenbaum BD, Li OT, Webby RJ, Poon LL. A statistical strategy to identify recombinant viral ribonucleoprotein of avian, human, and swine influenza A viruses with elevated polymerase activity. Influenza and other respiratory viruses 2013 Nov; 7(6).

Levine AJ, Greenbaum B. The maintenance of epigenetic states by p53: the guardian of the epigenome. Oncotarget 2012 Dec; 3(12).

Greenbaum BD, Li OT, Poon LL, Levine AJ, Rabadan R. Viral reassortment as an information exchange between viral segments. Proceedings of the National Academy of Sciences of the United States of America 2012 Feb; 109(9).

Jimenez-Baranda S, Greenbaum B, Manches O, Handler J, Rabadán R, Levine A, Bhardwaj N. Oligonucleotide motifs that disappear during the evolution of influenza virus in humans increase alpha interferon secretion by plasmacytoid dendritic cells. Journal of virology 2011 Apr; 85(8).

Solovyov A, Greenbaum B, Palacios G, Lipkin WI, Rabadan R. Host Dependent Evolutionary Patterns and the Origin of 2009 H1N1 Pandemic Influenza. PLoS currents 2010; 2.

Greenbaum BD, Rabadan R, Levine AJ. Patterns of oligonucleotide sequences in viral and host cell RNA identify mediators of the host innate immune system. PloS one 2009; 4(6).

Trifonov V, Khiabanian H, Greenbaum B, Rabadan R. The origin of the recent swine influenza A (H1N1) virus infecting humans. Eurosurveillance 2009 Apr; 14(17).

Greenbaum BD, Levine AJ, Bhanot G, Rabadan R. Patterns of evolution and host gene mimicry in influenza and other RNA viruses. PLoS pathogens 2008 Jun; 4(6).

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Greenbaum did not report having any of the following types of financial relationships with industry during 2015 and/or 2016: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.

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