Interrogating T-Cell Mediated Mechanisms Underlying the Development of Atherosclerosis in Patients With Psoriasis
Principal Investigator: Patricia Nguyen, M.D.
Institution: The Board of Trustees of the Leland Stanford Junior University
Grant Mechanism: Discovery Grant
Funding Amount: $75,000
Project Start Date: August 1, 2024
Project End Date: July 31, 2025
Status: Active
Keywords: Comorbidity, CVD, Inflammation
Project Summary:
Coronary artery disease (CAD) happens 150% more often in psoriatic patients. Why CAD occurs more often in psoriatic patients remains unclear. We think that the special immune cells called T cells cause both psoriasis and CAD. We think the same trigger activates T cells in both the skin and vessel. We will analyze the T cells in both the skin and aorta of the mice that have psoriasis and CAD. We will then grow “vessels” from stem cells collected from psoriasis patients. We will add the T cells that are specific to the trigger and see if the T cells activate and damage the “vessel”. If we find this trigger causes disease, then we can make treatment to block the trigger.
How will your project help improve the lives of the 125 million affected by psoriatic disease?
My project will help determine a mechanistic link between psoriasis and coronary artery disease (CAD). CAD is an important cause of morbidity and mortality in psoriatic patients. Our studies suggest that CAD may be caused by autoimmunity in some patients. This hypothesis is supported by studies showing that biologics reduce both the severity of skin disease and major adverse cardiac events. We hope to find the disease-causing antigen for psoriasis-induced atherosclerosis so that we may develop therapy to block this antigen.
Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?
Autoimmune diseases like psoriasis have personally affected my life. I suffer from atopic dermatitis, which is also associated with cardiovascular disease. Like atopic dermatitis, psoriasis is a disease of T cell dysregulation. In my earlier work, I have found that T cells were clonally expanded in patients with atherosclerosis, which suggests a shared antigen can contribute to the development and progression of atherosclerosis. Using a systems immunology approach, I will determine whether mechanisms of disease progression in psoriasis are also shared with atherosclerosis. This award will enable me to network with leaders in the psoriasis community and provide me preliminary data for an R01 proposal.
Researcher Profile:
Dr. Patricia Nguyen was born in Saigon, Vietnam and immigrated with her family to the United States. She graduated from Johns Hopkins Medical School and completed her residency at Columbia University and her cardiovascular training at Stanford University. Following her clinical fellowship, she worked in the laboratory of Dr. Joseph Wu to evaluate the efficacy and safety of stem cell therapies. Her research currently focuses on deciphering the immune-mediated mechanisms underlying cardiovascular diseases including atherosclerosis associated with psoriasis, using a systems immunology approach and applying novel techniques in molecular imaging, iPSC technology, single-cell sequencing, and computational biology.