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Researcher | Research Overview

Michael Farzan’s laboratory focuses on the generation and delivery of antibodies and antibody-like entry inhibitors for the prevention and treatment of infectious diseases, especially those caused by coronaviruses, arenaviruses, and retroviruses. We are especially committed to approaches that could prevent new viral infections and establish a functional cure for HIV-1. To do so, we develop and apply three main technologies. First, we use now well-established mRNA vaccines to deliver antigens informed by a detailed analysis of critical epitopes of the viral entry protein and properties of human immune repertoire.

Second, we use adeno-associated virus (AAV) vectors to express antibodies and antibody-like proteins that can control an established infection. Finally, we have committed to a long-term effort to combining ex vivo and in vivo editing technologies of B cells with novel vaccines and vaccination strategies. Here we modify the B-cell receptor loci of primary B cells, engraft these edited B cells back to their host, and expand these cells with antigenic stimulation. This technology allows us to use murine germinal centers to select potent and highly bioavailable human antibodies. It also provides us useful animal models to evaluate and improve vaccines, as well as a new way to address unanswered questions in B-cell biology. Finally, the chimeric antigen receptor (CAR) B cells so generated can themselves be conceived of as a therapy for many disease states including HIV infection.

Researcher | Research Background

Dr. Farzan received his undergraduate degree from Harvard College in Government and his Ph.D. in Immunology from Harvard Medical School (HMS), mentored by Dr. Joseph Sodroski. He received his first faculty appointment in the HMS Department of Medicine in 2002 and was promoted to professor in the Department of Microbiology and Immunobiology in 2012. He then spent a decade as co-Chair and then Chair of the Department of Immunology and Microbiology at the Scripps Research Institute on its Florida campus, returning to HMS in 2023 as Professor of Pediatrics and as the Director of Virology Research in the Division of Infectious Diseases at Boston Children’s Hospital.

He has studied for years the HIV-1 entry process and its inhibition, for example identifying the critical role of coreceptor tyrosine-sulfation in the entry process, and discovery of the same modification on HIV-1 neutralizing antibodies. This work led to the development of the broad and potent entry inhibitor eCD4-Ig and to his current effort to the epitopes of sulfated antibodies to drive protective antibody responses to HIV and other viruses. The recent interest in coronaviruses has also highlighted his work on SARS coronavirus (SARS-CoV) including identification of the receptor ACE2, delineation of the S protein receptor-binding site, and characterization of the molecular events necessary for this virus to move from palm civets to humans.
 

Researcher | Publications