Clinicn Investigator, Assc Prf Ragon PIs 2, Mass General Research Institute

Associate Physician Infectious Disease, Massachusetts General Hospital

Associate Professor of Medicine Harvard Medical School

MD New York University School of Medicine 2004

16s; antifungal agents; beta-defensins; cd4-positive t-lymphocytes; cd8-positive t-lymphocytes; contraceptive agents female; coronavirus; covid-19; diagnostics; female genital tract; hiv; hiv and tuberculosis; hiv infections; hiv-1; interleukin-10; intestinal immunity; lactobacillus; lectins; lectins c-type; microbiome; mycoses; rna ribosomal; triazoles; up-regulation; vagina

Mucosal surfaces represent both the primary site of HIV transmission and the largest reservoir of viral replication. Despite this, the immune response to HIV has largely been studied in the peripheral blood, which contains just 2-3% of all lymphocytes- a small minority relative to the 60-90% of the body’s T and B cells that reside at mucosal sites.

One of the greatest barriers to a more detailed understanding of these responses is the inherently small amount of material that can be obtained from mucosal sampling. We are therefore employing new technologies, such as high throughput sequencing and nanowell technologies developed by our collaborators at the Massachusetts Institute of Technology, to simultaneously capture multiple measures of viral, metagenomic, metatranscriptomic, culturomic and adaptive immune factors important for HIV immunity and pathogenesis.

Using these methodologies we have begun to map microbial communities and mucosal immune responses in the lung, female reproductive tract, and gut associated lymphoid tissue (GALT), at a level of resolution that has not been possible employing standard assays. This work is being performed using the large, well characterized patient cohorts available at the Ragon Institute to better understand susceptibility to HIV acquisition and HIV disease progression.

We also perform a significant amount of work in Africa in collaboration with the University of KwaZulu Natal HIV Pathogenesis Program, KRITH, CAPRISA, FRESH, and the University of Cape Town, to better understand the HIV epidemic in the developing world.