GLUT1 Inhibition by Lipid Nanoparticle (LNP) siRNA and Phloretin as Novel Treatments for Psoriasis
Principal Investigator: Richard Wang, M.D., Ph.D.
Institution: The University of Texas Southwestern Medical Center (UT Southwestern)
Grant Mechanism: Discovery Grant
Funding Amount: $75,000
Project Start Date: August 1, 2024
Project End Date: July 31, 2025
Status: Active
Keywords: Psoriasis, Animal Models, Disease Etiology, Drug Therapy, Disease Models, Immunology
Project Summary:
The GLUT1 glucose transporter is overexpressed in psoriasis. We previously found that its deletion prevented psoriasis in mouse models. We will advance GLUT1 inhibition as a therapeutic target in patients in two ways. First, we will develop novel lipid nanoparticles (LNPs) to deliver small-interfering RNA (siRNAs) to target GLUT1 and then test them in mouse models of psoriasis. Second, we will test whether phloretin, currently sold as a topical antioxidant, may also function as a GLUT1 transport inhibitor and novel treatment for psoriasis. This proposal has the potential to identify new therapies for psoriasis patients, broaden our understanding of psoriasis, and provide preliminary data for funding from other agencies.
How will your project help improve the lives of the 125 million affected by psoriatic disease?
Our project will advance two novel therapies for patients with psoriasis. The treatment strategy has already shown promise in vitro and in animal models. Importantly, both treatments target the abnormal glucose transport and metabolism present in psoriasis, which is not currently being addressed by any available therapies. This project will also advance the development of lipid nanoparticles which could theoretically be used to target a number of disease-relevant pathways.
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 have seen the remarkable advances which research has offered for patients. Many patients with debilitating psoriasis and psoriatic arthritis have a completely different outlook on life when their disease is treated. However, I continue to see patients for whom current therapies have failed. It is my goal to continue to develop novel treatments for these patients with recalcitrant disease.
This award will also provide us much-needed support to move our discoveries in basic research towards clinical relevance. As a physician-scientist, it has always been my ultimate goal to make discoveries that impact the lives of patients.
Researcher Profile:
Richard Wang completed B.S. with Honors from Stanford University in 1998. He then enrolled in the Tri-Institutional M.D./Ph.D. Program and completed his graduate thesis with Titia de Lange at The Rockefeller University and received his M.D. from Cornell in 2006. He returned to Texas to complete a residency in dermatology at UT Southwestern Medical Center in Dallas. After completing a postdoctoral fellowship with Beth Levine, he stayed on as faculty in the Department of Dermatology at UT Southwestern.
Dr. Wang runs a translational research laboratory. His research focuses on pathways central to both the development of normal skin and non-melanoma skin cancer tumorigenesis. One area of focus includes the study of how glucose transport and metabolism become dysregulated in inflammatory skin diseases, including psoriasis. Research in the laboratory has been supported by the Dermatology Foundation, the Burroughs Wellcome Fund, the American Cancer Society, NIAMS, and the NCI. Dr. Wang maintains an active clinical practice where he sees general dermatology patients and has an interest in immunosuppressed patients with inflammatory and infectious skin diseases.