NPF-Funded Research

Project Summary:

Psoriasis is a prevalent chronic inflammatory disorder of the skin, and is associated with multiple comorbidities such as arthritis, colitis and cardiovascular disease. While new biologic therapies revolutionized psoriasis treatment, mechanisms of psoriasis pathogenesis and the link between skin and extracutaneous inflammation are not well understood. We recently discovered that aberrant epithelial lipid peroxidation and ferroptotic cell death initiate and maintain psoriasis, psoriatic arthritis and associated heart disease. Supported by our published and new results, we will determine how keratinocyte ferroptosis leads to skin and extracutaneous psoriasis-associated inflammation, and test new therapies which target this mechanism.

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

Successful completion of this work will advance our understanding of psoriasis and psoriatic arthritis pathogenesis by elucidating how dysregulated keratinocyte lipid peroxidation initiates and sustains chronic cutaneous and extracutaneous inflammation. If our hypothesis is validated, identifying this pathway as a fundamental driver of disease would have substantial conceptual and therapeutic significance. These findings would provide a strong rationale for developing an entirely new class of psoriasis therapies targeting dysregulated enzymatic lipid peroxidation, with the potential not only to suppress chronic cutaneous inflammation but also to prevent or reduce psoriasis-associated comorbidities. Ultimately, this work may establish keratinocyte lipid peroxidation as a unifying therapeutic target linking skin disease to systemic inflammation.

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

As a dermatologist, I care for patients living with psoriatic disease and its associated comorbidities, and I see firsthand the substantial impact these conditions can have on quality of life. Advancing our understanding of the mechanisms that drive psoriatic disease is therefore an important goal for me, both personally and professionally, with the ultimate aim of developing more effective therapies and improving outcomes for these patients. Moreover, the mechanistic insights gained from our studies of psoriatic disease may have broader implications for understanding other chronic systemic inflammatory disorders in which epithelial dysfunction, lipid peroxidation, and inflammation intersect. Support from the National Psoriasis Foundation will be instrumental in advancing these investigations and enabling us to uncover new mechanisms of psoriatic disease pathogenesis that may ultimately lead to novel therapeutic strategies.

Researcher Profile:

Dr. Bunimovich is an Associate Professor of Dermatology and Immunology at the University of Pittsburgh Medical Center. He is a physician-scientist, trained at the UCLA/Caltech Medical Scientist Training Program (MSTP), where he obtained PhD in Chemistry and Chemical Engineering from the California Institute of Technology, completing his medical degree at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo. He completed his postdoctoral fellowship in Molecular and Medical Pharmacology at the California NanoSystems Institute and the Crump Institute for Molecular Imaging at UCLA.