Some of the most impactful work on rheumatoid arthritis (RA) pathogenesis has come out of the Brigham. The current division chief, Ellen M. Gravallese, MD, and former division chiefs, K. Frank Austen, MD and Soumya Raychaudhuri, MD, PhD, are among our faculty who have made significant contributions in understanding the origin and development rheumatic and allergic diseases.
The following is a brief look at our faculty's work in basic and translational research.
Studies of T cell function examine cytokine production, granzyme activities, B cell helper function and a range of interactions with other leukocytes. B cell biology includes antigen specificity and regulation of antibody and cytokine production. We are defining macrophage activation pathways and abnormal states in disease. Studies of stromal biology are revealing how fibroblasts enable and regulate chronic inflammation. Integrative analysis examines cell-cell interactions in normal and pathologic inflammation.
Investigators are studying a range of basic topics in cell biology, including translation, post-translational modifications, intracellular transport, signal transduction, cell stress events and cell death mechanisms. The results are advancing a fundamental understanding of cell biology. Insights from these studies are also being applied to understanding physiologic processes that underlie immune function along with pathologic conditions that contribute to immune diseases.
Advances in genomics and other high-dimensional assays has made it possible to generate large, complex datasets in pursuit of understanding human disease. These data require sophisticated computational algorithms to decipher as well as methods to integrate and cross-reference results with other external data. Our group has developed methods in genetics, transcriptomics, single cell transcriptomics, bibliomics and a wide range of other data modalities.
We are leading the way in using high-dimensional genomics, including single-cell transcriptomics and single-cell epigenomics, to define the key cellular components underlying complex disease. In addition, we are using these techniques to deeply phenotype human diseases. These powerful approaches have given us a view of the key immune and stromal cell states underlying rheumatic disease.
We are aiming to discover fundamental mechanisms of inflammation in rheumatic diseases and to dissect the impact of these inflammatory pathways on bone. This work has led to an understanding of the key pathways by which inflammation impacts bone in rheumatic diseases and has contributed to the change in focus in the treatment of these diseases, with a major focus on early intervention and disease modification. We are also studying the role of innate immune DNA-sensing pathways in autoimmunity and bone.
We are using single cell RNA-seq, single cell ATAC-seq, Nuc-seq, CyTOF, spatial transcriptomics, flow cytometry and other high dimensional analysis to deconstruct the cell types, cell states and interactome in inflamed human tissues in RA, lupus and other diseases. This discovery-based approach is identifying a host of abnormal cells and pathways that drive end organ damage.
We are using a variety of mouse models of inflammatory arthritis, lupus, spondyloarthritis, osteoarthritis and vasculitis to interrogate mechanisms and test therapeutic opportunities in rheumatic diseases
Since the publication of the Human Genome Project, it has become possible to use large human cohorts, rapid genome genotyping and sequencing and advanced statistical genetics to map risk alleles for a wide range of human diseases. Our group has been paving the way in mapping alleles for RA, other rheumatic diseases and infectious diseases. Besides mapping 100+ risk alleles, we are defining genetic mechanisms and developing strategies to use these genetic results to enhance clinical care.
For over a century, a leader in patient care, medical education and research, with expertise in virtually every specialty of medicine and surgery.
About BWH
