Award: Arthritis and Related Autoimmune Disease Research Grant
Biography: Wei Li, Ph.D., is an Instructor in Medicine at Beth Israel Deaconess Medical Center, Harvard Medical School, specializing in immunology and immunometabolism. His research focuses on how metabolic pathways regulate T cell function and contribute to autoimmune diseases, particularly systemic lupus erythematosus (SLE).
Dr. Li received his Ph.D. in Immunology from Beijing Normal University, where he studied the immunosuppressive effects of natural compounds in lupus models. He subsequently completed postdoctoral training at the University of Florida under Laurence Morel, where he investigated how lupus susceptibility genes influence T cell metabolism and function. His work identified key roles for genes such as Esrrg and Pbx1 in regulating immune responses and promoting autoimmune pathology. He further expanded his expertise at St. Jude Children’s Research Hospital with Hongbo Chi, focusing on mitochondrial regulation of T cell fitness. Currently, in the laboratory of George Tsokos, Dr. Li studies how the pentose phosphate pathway (PPP) and phosphatase signaling control immune tolerance. His recent work identified gluconolactone as a metabolite that enhances regulatory T cell function and demonstrated therapeutic efficacy in lupus models and patients.
Dr. Li’s research integrates mouse models, human T cell assays, and metabolic interventions to uncover mechanisms of immune dysregulation. His long-term goal is to develop metabolism-based therapies to restore immune tolerance and treat autoimmune diseases.
Research Summary: Systemic lupus erythematosus (lupus) is an autoimmune disease in which the immune system mistakenly attacks the body’s own tissues, causing inflammation and damage to organs such as the skin, joints, and kidneys. One reason lupus develops is because the immune system loses the ability to control itself. Special immune cells called regulatory T cells, or Tregs, normally act as “brakes” that prevent excessive immune responses. In people with lupus, these Tregs do not work properly, but the reasons for this are not fully understood.
Recent research shows that immune cells need the right kind of energy and nutrients to function normally. Changes in how immune cells use energy—called metabolism—can strongly affect whether these cells become harmful or protective. Our previous studies found that a natural metabolic pathway, known as the pentose phosphate pathway, helps Tregs develop and function correctly. We also discovered that a key enzyme in this pathway, called PGLS, is reduced in Tregs from lupus patients.
In this project, we will study how PGLS controls Treg function and how its loss contributes to lupus. Using mouse models and immune cells from lupus patients, we will determine how changes in metabolism weaken Tregs and promote inflammation. Understanding this process may reveal new ways to restore immune balance. This research is important because it could lead to safer, more targeted treatments for lupus by strengthening the body’s own immune regulation instead of broadly suppressing the immune system.