Award: Arthritis and Related Autoimmune Disease Research Grant
Biography: Dr. Holly Wobma is a pediatric rheumatologist and physician-scientist dedicated to developing next-generation cellular therapies for autoimmune and inflammatory diseases. Her research focuses on engineering immune cells to restore tolerance and selectively modulate pathogenic immune responses, with the goal of transforming treatment paradigms for conditions such as juvenile idiopathic arthritis and lupus.
Dr. Wobma’s work centers on the design and optimization of chimeric antigen receptor (CAR) T cell platforms, including regulatory T cells (CAR-Tregs), to target key drivers of immune dysregulation. By integrating insights from immunology, translational medicine, and cellular engineering, she aims to create therapies that are antigen specific and durable, minimizing systemic immunosuppression while preserving protective immunity.
In addition to her research program, Dr. Wobma is actively engaged in clinical care and co-directs a refractory arthritis clinic. Her clinical experience directly informs her scientific approach, ensuring that her work remains grounded in unmet patient needs and real-world therapeutic challenges. Her long-term goal is to bring innovative, precision-based cellular therapies into clinical practice to improve outcomes and quality of life for patients with autoimmune disease.
Research Summary: Rheumatoid arthritis (RA) is a common autoimmune disease that affects close to 1.5 million adults in the United States. In RA, the immune system mistakenly attacks the joints, causing pain, swelling, and long-term damage. Current treatments can reduce inflammation but must be taken indefinitely and often weaken the immune system, increasing the risk of infection. There is a critical need for novel therapies that restore lasting immune balance rather than suppress immunity.
Regulatory T cells, or Tregs, are specialized immune cells that normally keep inflammation under control and prevent autoimmunity. In RA, Tregs are present but are not strong enough to fully restrain harmful immune responses. One promising strategy is a Treg-based cellular therapy, in which patients receive additional Tregs to reinforce immune regulation. In this project, we will also genetically engineer Tregs to make them more effective for RA by adding a targeting molecule called a chimeric antigen receptor (CAR).
These CAR-Tregs are designed to recognize CD40L, a protein expressed on overactive immune cells in RA, particularly inflammatory T cells. This targeting allows CAR-Tregs to directly suppress disease-driving T cells and interrupt inflammatory signals that damage joints. We will test human CD40L-targeted CAR-Tregs using stored immune cells from RA patients to measure their ability to suppress T-cell activation and inflammatory signaling. We will then compare mouse CAR-Tregs to non-targeted Tregs in two mouse models of arthritis, testing treatment at both early and established stages of disease. If successful, this work will advance cell-based therapies aimed at curing RA.
Links:
https://www.childrenshospital.org/providers/holly-wobma