Immune Cell Contributions to Inflammatory Arthritis
Principal Investigator: Nicole L. Ward, Ph.D.
Institution: Vanderbilt University Medical Center (VUMC)
Grant Mechanism: R01 Bridge Grant
Funding Amount: $100,000
Project Start Date: August 1, 2024
Project End Date: July 31, 2025
Status: Active
Keywords: Psoriatic Arthritis, Comorbidity, Inflammation, Immunology, Disease Models, Cell Biology
Project Summary:
Psoriatic arthritis is a debilitating yet poorly understood joint disease that affects ~1 million Americans. Using a newly engineered mouse model of psoriatic arthritis, joint tissues from psoriasis patients, and cutting-edge transcriptomics technologies, we will determine whether B cells, a class of immune cells long overlooked in the psoriasis field, are essential drivers of psoriatic arthritis. The results of this research will bring clarity to the longstanding questions of how psoriatic arthritis arises, why it does not respond to many of our current therapies for psoriasis of the skin, and what existing FDA-approved agents may be repurposed to treat this devastating disease.
How will your project help improve the lives of the 125 million affected by psoriatic disease?
Collectively, our studies will identify B cells as new pathogenic contributors to PsA etiology and will identify the cellular mechanisms mediating B cell-T cell interactions that promote inflammatory arthritis. Our ability to translate and confirm our preclinical findings to PsA patients may lead to a paradigm shift in understanding PsA pathogenesis and repurposing existing FDA-approved drugs for treating PsA. The results of this research will bring clarity to the longstanding questions of how psoriatic arthritis arises, why it does not respond to many of our current therapies for psoriasis of the skin, and what existing FDA-approved agents may be repurposed to treat this devastating disease.
Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?
I grew up picking scale off my father's scalp while we watched NCAA basketball games on the television. My siblings and I knew growing up that our dad had red, scaly rashes on his knees, calves, elbows, and scalp, that it wasn't contagious, and it was from something called "psoriasis". Fast-forward a couple of decades and I have created a mouse model that develops red, flaky skin as a result of genetically over-expressing a transgene and all of a sudden I am immersed in studying the etiology and pathogenesis of psoriasis. Kismet. I have continued to study cutaneous psoriasis since then, and have recently become deeply interested in learning more about how psoriatic arthritis develops, and whether the mechanisms mediating arthritis are similar or different from the skin. Skin and joint disease significantly impact patients and their quality of life, and I am committed to better understanding the cause of these diseases with the long-term goal of adding new insight into disease pathogenesis and potentially identifying new targets for drug development. This Bridge Award will allow my team to generate critical new preliminary data that will address NIH Reviewer comments and allow us to revise and resubmit a large ~$4.2mill grant application that will identify B cells as new pathogenic contributors to PsA etiology and will identify the cellular mechanisms mediating B cell-T cell interactions that promote inflammatory arthritis. Our ability to translate and confirm our preclinical findings to PsA patients may lead to a paradigm shift in understanding PsA pathogenesis and repurposing existing FDA-approved drugs for treating PsA.
Researcher Profile:
Dr. Ward is a Professor and the Vice-Chair of Basic Research in the Department of Dermatology. She joined the department in January 2022 after working at Case Western Reserve University in Cleveland for more than 18 years. Dr. Ward completed her undergraduate, graduate and fellowship training in Canada before moving to Cleveland in 2003. Her active research program is focused on understanding the cellular and molecular pathogenesis of chronic inflammatory skin diseases, like psoriasis and psoriasis-related comorbidities. Her lab specializes in generating and studying unique mouse models of inflammatory skin disease. Her group has published several seminal findings including being the first to show that chronic skin-initiated inflammation can drive the development of cardiovascular disease and that suppressing it reverses disease; and that cutaneous sensory nerve interactions with dendritic cells are critical for eliciting and sustaining psoriasis pathogenesis, thus explaining the cellular mechanisms underlying psoriasis disease remission following skin denervation. Her paradigm-shifting work in psoriasis resulted in her being awarded the Eugene M. Farber Lecture at the 2016 Society for Investigative Dermatology meeting. She was the first non-MD, first woman and youngest person to be awarded this honor. In 2019, the American Skin Association acknowledged her scientific contributions with the Research Achievement Award in Psoriasis, in 2022 the National Psoriasis Foundation honored her at their Women Who Lead Commit to Cure Gala and in 2023 named her an NPF Distinguished Senior Investigator for Basic Science. Dr. Ward trains, teaches, and mentors undergraduate, graduate and medical students, residents, post-doctoral fellows, and junior faculty. At any given time, Dr. Ward’s lab is usually found to be surprisingly small. However, it is also often referred to as “small but mighty”.