Benhur Lee, MD
- PROFESSOR | Microbiology
Research Topics:Antibody Development, Antivirals, Biodefense, Blood-Brain Barrier, Cell Biology, Dendritic Cells, Drug Design and Discovery, Endothelial Cells, Epithelial Cells, Gene Therapy, Gene editing, Glycobiology, HIV/AIDS, Hematopoiesis, Infectious Disease, Interferon, Lung, Lymphocytes, Macrophage, Membranes, Microbiology, Nipah Virus, Nucleus, Paramyxovirus, Protein Trafficking & Sorting, Protein Translation, RNA, RNA Transport & Localization, Retrovirus, Stem Cells, Structural Biology, Systems Biology, Trafficking, Vaccine Development, Viruses and Virology, mRNA Decay
Dr. Benhur Lee is a Professor of Microbiology at the Icahn School of Medicine at Mount Sinai (ISMMS). He obtained his MD from Yale University School of Medicine (1995). He did his clinical pathology residency training at the Hospital of the University of Pennsylvania, where he also served as Chief Resident (2015-2019). His post-doctoral work Robert W. Doms, MD/PhD, at the University of Pennsylvania School of Medicine (1997-2001) established new concepts and standards for the HIV entry field that continue to inform current research on HIV vaccines and therapeutics. Prior to his recruitment to Mount Sinai in 2014 as the Ward-Coleman Chair in Microbiology, Dr. Lee was a full Professor in the Department of Microbiology, Immunology & Molecular Genetics at the David Geffen School of Medicine at UCLA (2001-2013).
Dr. Lee is a scientific advisor to the Standards Working Group (SWG) of the California Institute of Regenerative Medicine (CIRM, 2014-present), and is an appointed member of the NIH Recombinant DNA Advisory Committee (RAC) recently reconstituted as Novel and Exceptional Technology and Research Advisory Committee (NExTRAC) (2016-2020). He also an active member of the Paramyxovirus Study Group that is part of the International Committee on Taxonomy of Viruses (talk.ICTVonline.org).
Dr. Lee’s lab still maintains a special interest in HIV but has pivoted to the study of highly pathogenic emerging RNA viruses. His lab has a strong focus on the molecular viral-host interactions that govern virus entry and budding (#ViralLeeLab). His guiding principle is to translate insights gained from basic studies on host-pathogen interactions into anti-viral therapeutics. His lab’s latest foray into translation science involves developing a highly efficient and robust reverse genetics system for paramyxoviruses, so as to facilitate development of paramyxovirus-based vectors for gene therapy and high efficiency gene editing. #ViralLeeLab collaborates with many investigators across the country and the globe.
Please visit the Benhur Lee Lab homepage (#ViralLeeLab) at:
Multi-Disciplinary Training AreasDevelopment, Regeneration, and Stem Cells [DRS], Immunology [IMM], Microbiology [MIC], Pharmacology and Therapeutics Discovery [PTD]
Culpepper Biomedical Scholar Award (2002-2005)
Dolph Adams Award 2006
Overall Research Themes
How viruses survive, proliferate and transmit within and between hosts is a testament to the past and present evolutionary battles between host and pathogen. The guiding objective of our research is to obtain and translate basic knowledge about viral entry and replication processes to therapeutic or interventional anti-viral strategies. We are particularly interested in developing novel methods, reagents, and therapeutics to address long-standing and intractable problems in our fields of interest. The general theme that unites the studies in our laboratory is Molecular Viral-Host Interactions. We have a special interest in enveloped virus entry and budding mechanisms, with an increasing focus on viruses that cause Emerging Infectious Diseases. We study highly pathogenic viruses, and use Henipaviruses and Human Immunodeficiency Virus-1 (HIV-1) as primary model systems to represent the pathogenesis of acute and chronic viruses, respectively. Henipavirus is a new genus of paramyxovirus discovered around the turn of the millennium. Hendra (HeV) and Nipah (NiV) virus are zoonotic viruses—transmitted to humans from their natural bat reservoir—that cause fatal encephalitis in 40-95% of infected patients. Since 2015, henipaviruses has been on the WHO R&D research blueprint list of the top 8-10 pathogens most likely to cause a pandemic. We discovered the receptors for henipavirus entry (Negrete et al, Nature, 2005; PLoS Pathog, 2006), characterized the structure and function of the receptor binding proteins from divergent henipaviruses recently identified in Africa (Lee et al, PNAS, 2015) and China (Rissanen et al, Nat Commun, 2017), as well as provided evidence that henipavirus spillover events may have already occurred in high-risk populations in Cameroon (Pernet et al, Nat Commun, 2014). We developed robust and efficient reverse genetics systems for all major genera of paramyxoviruses (Beaty et al, mSphere, 2017), so that we can interrogate the biology of paramyxoviruses, including the more common measles (Fulton et al, Cell Reports, 2015), mumps and parainfluenza viruses, on a genome-wide scale (Satoshi et al, in submission, 2019). Currently, we are leveraging our long-standing collaboration with Thomas Bowden’s structural biology group (Oxford University) and Mount Sinai’s unique arrangement with REGENERON (VelocImmune® mice) to develop fully humanized broadly neutralizing antibodies against the ever-increasing spectrum of divergent henipaviruses and other paramyxoviruses that still pose a threat to global public health. Paramyxoviruses are negative sense RNA viruses that replicate entirely in the cytoplasm. Their matrix proteins coordinate the assembly and budding of virions at the plasma membranes. In a discovery that exemplifies the motto of our lab that— “viruses are the best cell biologists”—we discovered that henipavirus matrix proteins contain functional nuclear localization and nuclear export signals. And that an ubiquitin-regulated nuclear sojourn is required for the proper targeting of matrix proteins to the secretory pathway and plasma membrane domains that serve as sites of virus assembly and budding (Wang et al, PLoS Pathog, 2010). The nuclear import and export signals, as well as the ubiquitin-regulated nuclear transit, are conserved across several genera of paramyxovirus (Pentecost et al, PLoS Pathog, 2015). The matrix interactomes of at least seven paramyxoviruses representing the major genera of paramyxoviruses have revealed a treasure of biologically interesting partners that hints at many non-structural functions of paramyxoviral matrix proteins, including the unexpected involvement of matrix in antagonizing Type I IFN responses (Bharaj et al, PLoS Pathog, 2016). HIV-1, the causative agent of AIDS, is also a zoonotic virus—transmitted from its natural chimpanzee reservoir—that exploded on the world scene in the early 1980s. HIV/AIDS remains a global pandemic. However, our increasing understanding of HIV/AIDS pathogenesis, and the availability of potent combinations of anti-HIV drugs, perhaps marks “the end of the beginning” in our fight to bring this pandemic under control. In addition to our past contributions, our current research in this area involves developing SeV vectors for highly efficient gene editing in primary human hematopoietic stem cells as part of the international “HIV cure” efforts (Park et al, Mol Ther- Meth Clin Dev, 2016 and WO2017/223330A1-WIPO (PCT)). Our SeV vector Is modular and deliver their transgenes transiently. Thus, we can incorporate all the latest advances in CRISPR-Cas technology in order to achieve highly efficient genome or epigenome modifications in relevant primary human cells such as neurons, astrocytes, hematopoietic stem cells, monocytes, dendritic cells, lung epithelial cells, iPSC, etc.