Award: Postdoctoral Research Fellowship
Biography: Dr. Kristen Mengwasser is a physician-scientist and rheumatologist at UCSF whose research focuses on understanding the immune mechanisms that drive autoimmune rheumatic diseases. She completed MD-PhD training in the Harvard/MIT MSTP program, where she trained in genetics with Dr. Stephen J. Elledge, followed by internal medicine residency at Brigham and Women’s Hospital and rheumatology fellowship at UCSF. She is currently a postdoctoral scientist in the laboratory of Dr. Alexander Marson at the Gladstone-UCSF Institute of Genomic Immunology, co-mentored by Dr. Mark Davis at Stanford. She is an Assistant Adjunct Professor in Rheumatology at Zuckerberg San Francisco General Hospital (ZSFG)/UCSF.
Dr. Mengwasser’s research uses high-throughput genetic screening, immune engineering, single-cell genomics, and human tissue model systems to study pathogenic immune responses in rheumatologic disease. Her ANRF-funded work focuses on developing human lymphoid organoids as a platform to study systemic lupus erythematosus and rheumatoid arthritis. This work will allow her to investigate how different B-cell-directed therapies reshape pathogenic immune cell states, and which B cell subpopulations most directly contribute to disease.
Research Summary: Systemic lupus erythematosus, or lupus, is a chronic autoimmune disease that causes the immune system to attack the body’s own tissues. Lupus most often affects young women and can damage the kidneys, joints, and other organs. While several treatments exist, the most effective medications cause serious side effects, and we still do not fully understand how these medicines work, or why some patients respond better than others.
A major challenge in lupus research is that many studies rely on mouse models, which often do not accurately reflect the human immune system. To address this gap, this project involves development of a human lymphoid organoid system to study lupus. These organoids are created from living human tissue and recreate key features of the human immunology in a dish. This allows us to study lupus directly in human immune cells, rather than in animals.
The goal of this proposal is to understand why some therapies produce deeper and longer-lasting improvement in lupus than others. The project focuses on identifying harmful immune cells that drive disease and determining which of these must be eliminated to achieve lasting remission. In particular, we will compare cellular immune therapies, such as CAR-T cells, with antibody-based treatments to understand why some approaches more effectively remove disease-causing immune cells.
By revealing how different treatments reshape the immune system at a detailed level, this research aims to guide development of safer, more precise therapies that eliminate problematic immune cells while preserving protective immunity. Ultimately, this work seeks to improve long-term outcomes for people living with lupus and related autoimmune diseases.
Links:
https://profiles.ucsf.edu/kristen.mengwasser
https://rheumatology.ucsf.edu/people/kristen-mengwasser