Investigating Costimulatory Pathways as an Immune Connection Between Psoriatic Skin and Joint Disease
Principal Investigator: Bahram Razani, M.D., Ph.D.
Institution: The Regents of the University of California, San Francisco
Grant Mechanism: R01 Bridge Grant
Funding Amount: $100,000
Project Start Date: August 1, 2025
Project End Date: July 31, 2026
Status: Active
Keywords: Psoriasis, Psoriatic Arthritis, Basic Science, Animal Models, Cell Signaling, Disease Models, Immunology, Prevention
Project Summary:
Why a third of patients with psoriasis develop arthritis is unclear. As skin inflammation often precedes arthritis by years, immune processes in the skin may trigger joint disease. To study how skin and joint inflammation are linked, we developed a new animal model based on a known human genetic risk factor. In this model, inflammation triggered in the skin leads to joint inflammation resembling Psoriatic Arthritis (PsA). Using this model, we identified a pathway critical for developing skin-triggered arthritis. This pathway is critical for immune cell communication, but its role in PsA is not known. We aim to discover how this pathway connects psoriatic skin and joint inflammation, potentially revealing new treatment strategies.
How will your project help improve the lives of the 125 million affected by psoriatic disease?
Our project is focused on understanding the ways by which psoriatic inflammation in the skin is linked to inflammation in other organs, especially joints. We aim to test how a specific immune pathway contributes to joint inflammation in a model of psoriatic disease. By doing so, we hope this leads to new methods of identifying individuals with psoriasis at higher risk for arthritis and finding new therapeutic strategies to prevent joint damage in people with psoriatic disease.
Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?
As a practicing dermatologist, I help take care of many patients with psoriasis. My patients’ personal experience with psoriasis along with their questions on its causes and treatments provide a strong inspiration for me in my research career. My underlying hope is to contribute to discoveries that make management of this condition more precise and effective. This award will provide key funding to advance our promising and exciting early findings as well as supporting my growth as a physician-scientist working to bridge patient care and basic research.
Researcher Profile:
Bahram Razani received a BA in Biochemistry at Rice University in Houston, TX and completed his MD/PhD in immunology at University of California – Los Angeles (UCLA). During his PhD training, he studied the mechanisms of negative feedback in MAP Kinases that mediate Noncanonical NF-kB signaling in the laboratory of Genhong Cheng. He went on to train in Dermatology at the University of California – San Francisco (UCSF). He has been on faculty in the Department of Dermatology at UCSF since 2017. During his early faculty appointment in the Department of Dermatology, he concurrently completed postdoctoral training under the mentorship of Averil Ma, where he studied ubiquitin-mediated mechanisms of negative regulation in innate immune signaling and their impact on tissue immune homeostasis. His laboratory uses mouse models to understand how dysregulation of innate immune signaling in keratinocytes regulates both cutaneous and systemic immunity. He has a specific interest in using mouse models to understand the immune pathogenesis of psoriasis and its systemic co-morbidities.