Transcriptional Regulation of Synovial Tissue Resident Memory CD8 T Cells

Principal Investigator: Paul Hsu, M.D., Ph.D.
Institution: The Regents of the University of California, San Diego

Grant Mechanism: Early Career Research Grant
Funding Amount: $50,000
Project Start Date: August 1, 2024
Project End Date: July 31, 2025
Status: Active
Keywords: Psoriatic Arthritis, Animal Models, Cell Biology, Disease Models, Immunology

Project Summary:

Psoriatic arthritis (PsA) is an autoimmune disease characterized by chronic joint pain, swelling, and damage and recurring flares of synovial inflammation. While new treatments are highly effective in treating PsA, most patients do not reach remission or are refractory to multiple lines of treatment. Recurrent flares are thought to be due to tissue-resident memory CD8+ T cells (TRM) that remain within the affected joints and skin. The cellular programming that instructs TRM to accumulate and stay in joints. FOXO1 is a transcription factor that is important for memory T cells, and controls the balance of resting and active cells. Understanding how FOXO1 controls synovial TRM and inflammatory arthritis may provide new strategies to treat PsA.

How will your project help improve the lives of the 125 million affected by psoriatic disease?

PsA is a common comorbid condition affecting approximately 20% of patients with psoriasis that causes inflammatory joint pain and disability. Tissue-resident memory T cells found in the skin and joints of patients contribute to disease flares and long-term persistence of lesions. Despite revolutionary biologic and oral small molecule therapy, less than 30% of patients experience complete remission after first-line therapy and require sequential therapy. However, targeting the mechanisms that underlie tissue residency is in its infancy, and may result in more durable therapies. Understanding how tissue residency is regulated in afflicted tissues is critical to developing novel effective and durable therapies and is of great clinical importance.

Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?

My research goals are influenced by my own diagnosis of PsA, my clinical experience caring for patients with lasting disability from inflammatory arthritis, and my desire to discover therapeutic alternatives to chronic immunosuppression. This pilot award is critical in supporting me during my transition following completion of my Rheumatology fellowship towards establishing my research program. This award provides support for studies that will distinguish me from my mentors, and will support my ongoing applications for career development awards.

Researcher Profile:

Paul Hsu, M.D., Ph.D. is a postdoctoral fellow at the University of California, San Diego (UCSD). He trained in both Internal Medicine and Rheumatology at UCSD. Dr. Hsu has been a staff physician at the Jennifer Moreno Department of Veterans Affairs Medical Center, where he cares for Veterans who are afflicted with PsA and other enteropathic arthritides. Dr. Hsu is mentored by John Chang, M.D., Professor of Medicine and Co-Director of the UCSD Program in Immunology, and Monica Guma, M.D., Ph.D., Professor of Medicine and Chair of the Division of Rheumatology, Autoimmunity, and Inflammation at UCSD. Dr. Hsu’s postdoctoral training is in the cellular programming of tissue-resident memory cells, and his research interests are the mechanisms of how chronic inflammatory arthritis is established and maintained.