Rheumatology, Inflammation, and Immunity Basic/Translational Research

Overview

Welcome to Basic and Translational Research in the Division of Rheumatology, Inflammation and Immunity at Massachusetts General & Brigham and Women’s Hospitals. The basic and translational research program aims to revolutionize the treatment of rheumatic diseases by uncovering the precise cellular and molecular origins of chronic inflammation and tissue damage. By combining cutting-edge genomic technologies with deep clinical insights, our investigators seek to identify novel therapeutic targets that can halt disease progression and restore immune balance. Working closely with colleagues in clinical research and clinical practice, this synergistic effort bridges the gap between laboratory discovery and patient care to develop personalized strategies for preventing and reversing autoimmune conditions.

The Basic and Translational Research program at Mass General Brigham is dedicated to deconstructing the cellular pathology of autoimmune and inflammatory diseases. By integrating single-cell transcriptomics, spatial genomics, and high-dimensional computational tools, our investigators identify the specific cellular "switches"—from pathologic T cell subsets and dysregulated myeloid cells to inflammatory fibroblasts—that drive tissue destruction.

Our research spans the spectrum of rheumatic health, including:

• Mechanistic and Translational studies in the rheumatic diseases.
• Cellular Mechanisms: Investigating RNA metabolism, intracellular transport, and ferroptosis in immune signaling.
• Tissue Dynamics: Defining the role of stromal cells and the "trained immunity" of macrophages in chronic inflammation.
• Bone & Joint Health: Elucidating the pathways governing bone damage and osteoclast regulation.
• Trigger Discovery: Examining how infections, commensal microbes, and lipid antigens initiate autoimmune responses.

Through these synergistic efforts at BWH and MGH, we aim to transform fundamental insights into precision therapeutics that restore immune balance and promote tissue healing.

Basic and Translational Research Principal Investigators

Brigham and Women’s Hospital (BWH)

Ellen M. Gravallese, MD (Division Chief)
Dr. Gravallese has identified key regulators of bone damage in rheumatic disease. Her current work investigates how innate DNA-sensing pathways regulate inflammation, and studies trained immunity and the role of macrophages in inflammatory arthritis.

Michael B. Brenner, MD
Dr. Brenner studies autoimmune diseases and is working to define the roles of pathologic T cells in inflamed tissues and their role in driving B cell differentiation and complement activation. He is defining Treg dysfunction and determining how to preserve functionality. He has identified inflammatory and destructive fibroblast populations and studies how to therapeutically modulate their behavior.

Paul Hoover, MD, PhD
Dr. Hoover uses single-cell approaches, CRISPR screens, and functional studies to decode immune dysregulation in autoimmune tissues. He targets myeloid cell mechanisms, seeking molecular switches that can interrupt damage and restore tissue function.

Victor Hsu, MD
Dr. Hsu’s lab studies two fundamental cellular processes, intracellular transport and ferroptosis (an iron-dependent form of cell death). Insights from these studies are contributing to understanding different pathologic conditions that include inflammation.

Tiffany Hsu, MD, PhD
Dr. Hsu investigates how autoantibodies targeting intracellular RNA-binding proteins like MDA5 activate inflammatory pathways, leveraging structural biology, biochemistry, and cellular immunology to uncover disease mechanisms in autoimmunity.

Pavel Ivanov, PhD
Dr. Ivanov studies RNA metabolism under cellular stress. He investigates how RNA-mediated stress responses contribute to human health and disease. His goal is to develop new RNA-based therapeutics based on manipulation of stress response pathways.

Christian Jacome-Galarza, PhD
Dr. Jacome-Galarza's lab studies the biology of monocytes, macrophages, and osteoclasts. His research focuses on the developmental cell origin, functions, and transcriptional regulation of these cells in arthritis, inflammation, and bone diseases, with the goal to identify signals that prevent inflammation, joint destruction, and promote tissue healing.

D. Branch Moody, MD
Dr. Moody played early roles in the discovery of human CD1-restricted T cells and their recognition of lipid antigens. Current research focuses on modulating human T cell responses in major autoimmune and infectious diseases and lipidomic analysis of cells.

Deepak A. Rao, MD, PhD
Dr. Rao uses high dimensional analyses to identify adaptive immune cell dysregulation in patients with rheumatic diseases, with a focus on regulation of disease-associated T cell populations including T peripheral helper (Tph) cells.

Soumya Raychaudhuri, MD, PhD
Dr. Raychaudhuri integrates computational and experimental genomics, using single-cell and spatial technologies, to define immune pathways in autoimmunity. He builds novel analytical tools to extract clinical insights from high-dimensional datasets.

Kevin Wei, MD, PhD
Dr. Wei’s lab focuses on deciphering the role of stromal cells in inflammatory and fibrotic diseases. His lab integrates single-cell transcriptomics, spatial transcriptomics, and patient-derived organoids to define key stromal cell pathways relevant to chronic inflammatory diseases.

Massachusetts General Hospital (MGH)

Cory Perugino, DO
Dr. Perugino identified key roles for CD4+ cytotoxic T lymphocytes (CD4+ CTLs) as drivers of tissue damage in rheumatic diseases, including IgG4-related disease and systemic sclerosis. A major current objective of his lab is to elucidate the cellular origins and molecular determinants of CD4+ CTL differentiation to identify targets for novel therapeutic development.

Gary Reynolds, MD, PhD
Dr. Reynolds uses computational approaches to understand why inflammation fails to resolve in rheumatic diseases. His clinical interest is vasculitis, and he applies the same methods to understand how we can prevent organ damage in these conditions.

Allen Steere, MD
Dr. Steere originally described Lyme disease. He now uses Lyme arthritis to study infection-triggered autoimmunity, and similarly, he is studying whether certain commensal microbes may trigger such responses in rheumatoid arthritis.