The National Institute of Allergy and Infectious Diseases has awarded an Ohio State researcher, previously published in Nature Medicine, a $2.5-million grant. The study, “Nedd4 in T helper cell development and autoimmunity,” will investigate ways to mediate and treat autoimmune diseases. Jian Zhang, MD, associate professor of Microbial Infection and Immunity, is principal investigator on the study.
In 2014, Dr. Zhang and his team discovered the foundation for the study: Nedd4 is required for the development of T helper (Th) 17. This molecule, if it is aberrantly activated or expressed, mediates certain autoimmune diseases such as multiple sclerosis. T cell-mediated autoimmunity is important because it embodies autoimmune T cell responses. The discovery of Nedd4 in Th17 cell development suggests that Th17 responses can be regulated. As a therapeutic target, the molecules Nedd4 could eventually treat autoimmune diseases that involve Th17.
Dr. Zhang says, “We eventually want to find a way to inhibit the Nedd4 function to achieve the therapeutic effect in patients.”
Autoimmune diseases under investigation by the medical research team involve the molecule Nedd4 regulating Th17. Th cells that produce IL-17 have different developmental and functional features than Th1 and Th2 cells.
Several methods are under way. The first method is an in-vitro approach to examine the molecular mechanism that causes Nedd4 to regulate Th17 in mouse and human T cells. The second method is an in-vivo approach that employs a mouse model. The third method investigates the mechanism behind Nedd4 regulation.
“Eventually we want to translate our findings from mouse models to humans,” explains Dr. Zhang.
The grant funding extends through May 2021. This is a subsequent review of his previous R01, a study from 2004. Dr. Zhang renewed the grant for the first time in 2010. This second review initiates the 11th year of the grant.
Collaboration with Dr. Zhang’s co-investigators, Amy Lovett-Racke, PhD, Professor in the Department of Microbial Infection and Immunity and Michael Racke, MD, Professor in the Department of Neuroscience will help translate the findings to human health.