Benjamin K Chen, MD, PhD
img_Benjamin K Chen
PROFESSOR | Medicine, Infectious Diseases
PROFESSOR | Microbiology
PROFESSOR | Pharmacological Sciences
Research Topics
Antivirals, Cell Adhesion, Cell Motility, Cytoskeleton, HIV/AIDS, Image Analysis, Imaging, Immune Deficiency, Immunology, Infectious Disease, Integrins, Lymphocytes, Lysosomes/endosome, Macrophage, Migration, Molecular Biology, Protein Trafficking & Sorting, RNA Transport & Localization, Retrovirus, Synapses, T Cells, Trafficking, Two-Photon Imaging, Vaccine Development, Viruses and Virology
Multi-Disciplinary Training Area
Cancer Biology [CAB], Disease Mechanisms and Therapeutics (DMT), Microbiology [MIC]
Current Students: MD/PhD: Chati Zony, Graduate: Natasha Durham, Kenneth Law, Hongru Li

Postdoctoral Fellows: Ray Alvarez, Anthony Esposito, Lili Wang

Research Faculty: Ping Chen, Talia Swartz                    

Summary of Research Studies:

Mechanisms of HIV cell-cell transmission

The efficiency of HIV spread in culture is greatly facilitated by cell contact between infected and uninfected CD4+ T cells. Infected T cells form adhesive contacts with uninfected CD4+ T cells. These contacts are called virological synapses (VS) because of similarity to other adhesive structures in the immune system call immunological synapses. VS require viral Env proteins to be expressed on the cell surface where they interact with CD4 on target cells.  Using infectious, fluorescent virus clones we are able to quantify and visualize the amount of viral transfer that occurs through VS.  Live, video rate confocal microscopy allowed us to visualize the changes in cellular distribution of the viral protein Gag that occurs during VS formation. We found that the VS causes the efficient transfer of viral particles into target T cells through an endocytic route that is still being characterized.  We are working to understand the viral signals that allow virus assembly to be recruited to the VS and the cellular signaling pathways the work in both the VS donor and target cells.

Neutralization Resistance of VS

The VS-mediated viral infection can be resistant to patient antibodies that are capable of neutralizing homologous cell free virus. We are working to understand how the VS provides a mechanism for HIV to evade humoral immune responses.  We found that the cytoplasmic tail of the Env glycoprotein, which is plays an important role in regulating fusion activity of Env, plays a role in the resistance of cell-cell infection to neutralization.  We are testing a model whereby the conformational regulation of Env during VS formation is what makes cell-cell transmission more resistant to neutralization.  We are studying patient neutralizing responses, and cloning B cells from patients to characterize potent cell-cell neutralizing activities.

Role of cell-cell transmission in vivo

We have been studying humanized mouse models to better understand how this mode of efficient viral dissemination contributes to viral spread in vivo. To overcome the inability of HIV to replicate in mouse cells, researchers have exploited mouse xenograft models that engraft human immune systems into immunocompromised mice. These mouse systems transplant human hematopoietic stem cells into immunodeficient mice and allow diverse lineages of human immune cells to develop.  Importantly, the human immune systems are highly susceptible to HIV and can support sustained HIV viral loads in animals that are challenged. In humanized mouse systems, we are using whole animal imaging and intravital microscopy to understand how T cell migration and synapse formation contribute to HIV spread within a living organism.

For more information, please visit the Benjamin K. Chen Laboratory.

BAS, Stanford University

MD, Weill Medical College of Cornell University

PhD, The Rockefeller University

Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology

2009

Avant Garde Award in HIV/AIDS research

National Institute of Drug Abuse, NIH

2007

Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases

2007

Irma T. Hirschl Monique Weill-Caulier Career Scientist Award

2000

National Research Service Award, National Institute for Allergy and Infectious Disease

National Institutes of Health

1990

Graduation with Honors in Biological Sciences

Stanford University

1990

Graduation with Distinction in Philosophy

Stanford University

Benjamin Chen, MD, PhD

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device, biotechnology companies, and other outside entities 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 outside financial relationships.

Dr. Chen has not yet completed reporting of Industry relationships.

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.