Associate Professor of Surgery, Harvard Medical School, Brigham and Women’s Hospital
Mark A. Perrella, MD
Associate Professor of Medicine, Harvard Medical School
Associate Physician, Brigham and Women’s Hosptial
Sailaja Ghanta, MD
Assistant Professor of Pediatrics, Harvard Medical School
Associate Physician, Brigham and Women’s Hospital
Restoring Immune Homeostasis and Recovery in Trauma by Trained Immunity
Traumatic injuries from burns, blasts, or major surgery dysregulate immune system function, predisposing injured people to life-threatening infections or persistent critical illness. Targeted therapeutics to restore immune function and homeostasis have not yet been developed for clinical use and are urgently needed. Dr. Lederer and his team believe that the diversity among human beings serves as justification for targeting evolutionarily conserved immune system regulatory networks in order to help restore immune system function after traumatic injuries. The research team uses these “innate” stimulatory networks to enhance immune system recovery from severe injuries and to prevent the development of life-threatening infections.
Dr. Lederer and his team target an immunological process known as trained immunity, which is the process of reprogramming innate immune cells to enhance their function. They discovered a type of immune stimulant called CpG-DNA — small pieces of DNA found in bacteria and cell mitochondria — that can activate a highly protective trained immunity response in mice exposed to high-dose radiation or burn trauma. CpG-DNA acts in the bone marrow to help regenerate immune cells that are better poised to respond to infections and eliminate bacteria in people that are severely injured or have a compromised immune system.
With Stepping Strong Center funding, Dr. Lederer and his team will test and develop novel CpG-DNA for immunomodulatory activity in mouse trauma models and will investigate how CpG-DNA mediates its trained immunity effects on mesenchymal stromal cells (MSCs) and hematopoietic stem cells (HSCs) to explore the potential of using CpG-DNA stimulated MSCs as a cellular therapy for immune dysfunction following traumatic injuries.
James Lederer, PhD, is an associate professor of surgery at Harvard Medical School. Dr. Lederer attended the University of Wisconsin, earning a Bachelor’s Degree in Bacteriology, a Master’s Degree in Microbiology, and a PhD in Immunology. His research focuses on the complexities of the body’s response to injury and disease by studying the effect of these insults on immune reactions in mice and humans. Dr. Lederer’s work extends beyond trauma immunology research into radiation injury, autoimmune diseases, lung inflammation, and tumor/cancer immunology.