Investigating the Mechanistic Role of TNFR2 in the Pathophysiology of Psoriatic Arthritis
Principle Investigator: Raminderjit Kaur, Ph.D.
Institution: Cleveland Clinic
Grant Mechanism: Early Career Research Grant
Funding Amount: $50,000
Project Start Date: August 1, 2022
Project End Date: July 31, 2023
Keywords: Psoriatic Arthritis, Animal Models, Disease Models, Immunology
According to the 2019 American College of Rheumatology/NPF treatment guidelines, anti-TNF inhibitors (TNFi) have been recommended as the first-line therapy for active psoriatic arthritis (PsA). Mechanistically, tumor necrosis factor-a (TNF-a) functions by activating two receptors: TNFR1 and TNFR2 when used in the treatment of psoriatic diseases. The TNFi blocks both TNF receptors, thus stopping both TNFR1 and TNFR2 activity. However, long-term use of TNFi can lead to higher incidences of adverse effects, including serious infections and malignancies, which are implicated in the inhibition of TNFR1 (as opposed to TNFR2). Thus, there is greater interest to see if a more selective TNF blockade could potentially yield a safer yet effective treatment. Our recent studies suggest that TNFR2 activity, but not TNFR1 activity drives psoriasis. In this proposal, we are testing the role of TNFR2 in psoriatic arthritis using mouse models and trying to identify novel molecular pathways of TNFR2 that may be responsible for the disease pathogenesis. Overall, this study may have far-reaching implications in developing more specific anti-TNFi by targeting TNFR2 activity rather than both receptors.
Dr. Raminderjit Kaur completed her Ph.D. in Molecular Biology & Biochemistry at Guru Nanak Dev University, India, and then moved to the U.S. and joined Cleveland Clinic as a Post-doctoral fellow to pursue her research interest of understanding the role of TNFR2 pathways in psoriatic diseases. Dr. Kaur studies under the mentorship of Dr. Elaine Husni, Vice Chair, Dept. of Rheumatic and Immunologic Diseases, Cleveland Clinic.