Elizabeth Fay Brigham Professor of Medicine, Harvard Medical School
Director of the Human Immunology Center at Brigham and Women's Hospital
Michael Brenner is the E.F. Brigham Professor of Medicine at Harvard Medical School and Director of the Human Immunology Center at BWH. He is a member of the National Academy of Sciences, USA, Fellow of the American Academy of Microbiology and the Fellow of the American Association for the Advancement of Science. In 2023 he was designated "Highly Cited Researchers" by Clarivate (top 1% of scientists by citation). He received the Lee C. Howley Prize for Research in Arthritis (Arthritis Foundation), the Distinguished Basic Investigator Award (ACR) and the Carol-Nachman Prize in Rheumatology. He served as chair and co-chair of the Accelerating Medicines Partnership RA/SLE consortium for 6 years and now serves as co-principal investigator of the new AMP-AIM consortium technology core. These studies are carrying out single cell and spatial transcriptomic deconstruction of RA, SLE, psoriasis and PsA and Sjogren’s syndrome.
Brenner's translational research accomplishments in RA include defining: 1) mechanisms of fibroblasts mediated joint inflammation and damage, 2) mechanisms of fibroblast activation, 3) role of cadherins and NOTCH signaling in fibroblast mediated pathology. He discovered new lymphocyte populations including 4) T peripheral helper T (Tph) cells that that drive B cell differentiation and antibody production and 5) Granzyme K CD8 T cells that are the dominant CD8 T cell phenotype in many chronically inflamed autoimmune tissue and drive complement activation.
Brenner's basic biology accomplishments include discovery of 1) γδ T cells, 2) the system of lipid antigen presentation mediated by CD1 molecules that bind and present lipid antigens for recognition by T cell receptors, 3) roles of CD1-restricted T cells in host defense and adipose tissue inflammation, metabolism and thermogenesis, 4) role of the αEβ7 integrin in mucosal leukocyte trafficking, 5) role of the molecular chaperone role of IP90 (calnexin) in TCR and MHC protein complex assembly, and 6) role of small GTPase Arl proteins in endocytic trafficking and antigen presentation.
We have implemented a disease deconstruction pipeline using single cell and spatial technologies applied to inflamed tissues in humans to discover new cell types, cell states and pathways that mediate autoimmune disease. We then use in vitro organoids, other reductionist approaches, and mouse models to define mechanisms and therapeutic insights for the new pathways and cell states. By shifting between humans and mice, our studies unravel the most relevant autoimmune and inflammatory abnormalities in vivo and then interrogate them in experimental systems. Over the past few years, we have identified new pathogenic T cell populations, macrophage states, and stromal cell subsets that drive pathology in autoimmune disease. Recently, we identified a new pathway of complement activation. These examples are described in the Research Focus section.
