Award: Arthritis and Related Autoimmune Disease Research Grant
Biography: Dr. Hoover is a dedicated rheumatologist and translational physician-scientist specializing in the treatment and laboratory-based investigations of autoimmune diseases. As the Director of Translational Research in Lupus Nephritis at Brigham and Women’s Hospital, he leads studies on the immune responses and the role of macrophages that contribute to tissue damage and repair in the kidneys and other organs affected by lupus and related autoimmune conditions. His lab employs advanced methodologies, including single-cell analyses, spatial technologies, and genomic perturbation strategies, utilizing both human samples and mouse models of disease. Dr. Hoover earned his medical degree and doctorate in molecular and cellular physiology from Stanford University School of Medicine. He completed his residency and fellowship in Rheumatology at Brigham and Women’s Hospital and conducted postdoctoral research at the Broad Institute. Through his research program, Dr. Hoover is working to translate cutting-edge discoveries into new therapeutic approaches for patients with autoimmune diseases.
Research Summary: Lupus nephritis is a serious kidney complication of lupus and a major cause of kidney failure and death. Immune cells called myeloid cells in the kidneys are likely important for both active inflammation and long-term scarring, but their exact roles are not well understood. This has made it difficult to develop treatments that precisely target these cells. We recently discovered new types of myeloid cells inside the kidneys of patients with lupus nephritis. One group of myeloid cells inside the filters of the kidney (glomeruli) is linked to active inflammation, while another group in the tissue between the filters (tubulointerstitium) is linked to scarring. Both groups sit next to scar-forming cells (myofibroblasts) and share a unique “injury response” program marked by a molecule called TREM2. We believe that these TREM2-positive cells gather in specific “neighborhoods” in injured areas, where they sense damage and coordinate how other immune and structural cells respond. In Aim 1, we will use advanced imaging on kidney biopsies from patients with active lupus nephritis to map exactly where these cells are located and which other cells they interact with. In Aim 2, we will study how these injury-associated myeloid cells and key kidney cells called mesangial cells influence each other using cells from patients. We will test whether these TREM2-positive myeloid cells push mesangial cells toward harmful scarring and abnormal immune activity. Our studies will reveal how specific immune cells inside the kidney drive damage in lupus nephritis and may point to new treatment strategies.