Award: Arthritis and Related Autoimmune Disease Research Grant
Biography: Dr. Alisa Mueller is an Assistant Professor in the Division of Immunology and Rheumatology at Stanford University with a dual appointment at the Palo Alto VA Medical Center. She earned her MD and PhD degrees at Stanford University as part of the Medical Scientist Training Program, where she investigated mechanisms regulating a mesenchymal progenitor population in skeletal muscles that mediates both healthy tissue regeneration and pathologic fibrosis. Subsequently, Dr. Mueller pursued an internal medicine residency and rheumatology fellowship at Brigham and Women’s Hospital and Harvard Medical School, where she explored mechanisms driving synovial fibroblast pathogenicity in rheumatoid arthritis. Her work led to the identification of non-canonical WNT signaling as a critical mediator of RA synovial fibroblast inflammatory activation. She also developed functional genomic screens to elucidate a broad set of novel therapeutic targets in inflammatory fibroblasts. Additionally, in partnership with the Undiagnosed Diseases Network, Dr. Mueller has led high-dimensional immunoprofiling studies to elucidate biological mechanisms catalyzing disease in patients with long standing immune related disorders of unknown etiology. As a physician-scientist, Dr. Mueller now leads an independent research laboratory investigating mechanisms that drive stromal pathology and rheumatoid arthritis and other chronic inflammatory conditions. Using innovative techniques in immunology, genomics, and regenerative medicine, She and her team aim to develop novel therapeutic approaches to combat immune diseases.
Research Summary: Rheumatoid arthritis (RA) is a painful disease that causes joint swelling and damage. In RA, certain cells that form the structure of the joints, called fibroblasts, become overactive and cause inflammation. Current treatments for RA don’t target these cells directly. Our team found a protein called SIX1 that might control how fibroblasts become overactive in RA. We aim to study SIX1 to see if it could be a new target for RA treatment. Our research has three main goals. First, we will find out which genes are controlled by SIX1 using fibroblasts from RA patients. Next, we will see how increasing or decreasing SIX1 affects the harmful activities of these cells. Finally, we will test if blocking SIX1 can reduce arthritis in a mouse model. In our studies, we’ll use advanced lab techniques to study SIX1 in human cells and mice with arthritis. These methods will help us understand how SIX1 works and if stopping it can reduce inflammation. If our research is successful, we hope it will lead to new treatments for RA that work differently from current medicines. These new treatments might be especially valuable for patients whose RA doesn’t improve with existing treatments.