NPF-Funded Research

Project Summary:

Psoriasis is a lifelong inflammatory skin condition that causes painful, itchy, red plaques and affects millions of people and decreases their daily quality of life. Although some effective psoriasis treatments have been recently defveloped, ongoing research is still needed to develop options that work safely and reliably for everyone. This project explores a new treatment approach that strengthens the skin’s own cannabinoid system, which helps control inflammation and inhibit skin cell growth. Using a well-established mouse psoriasis model, we will test whether this new drug, LEI-515, decreases disease severity and reduces itch. Our hope is that this research will support the development of more targeted, skin-focused therapies to improve the lives of people living with psoriasis.

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

Completing this project will help clarify whether targeting the body’s endocannabinoid system could lead to better treatments for people living with psoriatic disease. The project determines whether an experimental therapy LEI-515 (which boosts the body's endocananbinoid system) can reduce psoriasis-like skin inflammation and associated symptoms in a mouse model of psoriasis, while examining changes in inflammatory pathways and naturally occurring lipid signals in the skin and blood. Experiments using mice lacking CB2 globally or specifically in skin cells will establish whether the beneficial effects of LEI-515 depend on this receptor, helping us understand how and why the treatment works and if topical therapy may be advantageous. By establishing this biological foundation, these studies may identify new treatment targets and biomarkers to guide future studies aimed at developing more precise therapies that reduce disease burden and improve quality of life for 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?

Psoriatic disease affects millions of people and can have a profound impact on health and quality of life, yet there remains a need for additional treatment options. Our laboratory has a strong research interest in the endocannabinoid system, a natural signaling network that plays an important role in maintaining skin health by regulating inflammation, skin cell growth, and itch. This NPF award gives us the opportunity not only to translate our expertise in cannabinoid biology into testing a promising new therapeutic approach for psoriasis, but also to support Dr. Eva Wisniewski, a postdoctoral fellow in our laboratory, in further developing her research focus in dermatology.

Researcher Profile:

Dr. Ken Mackie, the Principal Investigator of this NPF-funded project, is a Distinguished Professor of Psychological and Brain Sciences and Linda and Jack Gill Chair of Neuroscience at Indiana University Bloomington. He received his MD from Yale University, completed his residency in anesthesiology at the University of Washington, and pursued postdoctoral training at Rockefeller University and the University of Washington. For more than three decades, his research has focused on understanding the endocannabinoid system and the effects of cannabinoids, including their potential therapeutic applications. His laboratory combines molecular, biochemical, imaging, electrophysiological, and behavioral approaches to understand cannabinoid signaling in health and disease. In 2023, Dr. Mackie and colleagues established Indiana University’s Center for Cannabis, Cannabinoids and Addiction to advance cannabinoid research and provide cutting-edge resources for preclinical and clinical studies.

Dr. Mackie will lead this project in collaboration with Dr. Eva Wisniewski, a postdoctoral fellow in his laboratory. Dr. Wisniewski received her medical and doctoral degrees from Semmelweis University in Budapest, Hungary, and joined Dr. Mackie’s laboratory in 2022. Since then, she has focused her research on understanding how the endocannabinoid system influences inflammatory skin diseases, including psoriasis. With a background in immunology and a long-standing interest in dermatology, she is particularly interested in translating discoveries in cannabinoid biology into new approaches for treating skin disease. She plans to pursue a career combining clinical dermatology with translational research, and this project represents an important step toward that goal.