Research Programs at the MGH Immunobiology Lab
Basic Science Programs
The Immunobiology Laboratory investigates the mechanisms by which self-reactive cells (the cells that mistakenly attack the body’s own healthy tissues) end up the blood to eventually find and destroy the cells of the pancreas or other organs. We also study how these abnormal cells might be selectively killed, in culture (test tubes) and in people, once they are abnormally formed by the immune system.
We study both humans and mice with autoimmunity. If we see the same defects in humans with autoimmunity as we see in mice with the disease, we know we are on the correct track to move our discoveries forward.
In 2001, our lab discovered that the mouse pancreas could regenerate if the self-reactive T cells were selectively killed in animals with advanced type 1 diabetes. We continue to study pancreas regeneration, including studying the adult stem cells of the spleen that can directly or indirectly contribute to regeneration. In mice, we have demonstrated that these cells are capable of speeding the rate of pancreas healing once the faulty immune system is repaired. We will continue to explore the potential role of the spleen as a reservoir for adult stem cells in animals and humans, work that may be relevant in the future for people with advanced autoimmune disease, where the regenerative potential may be hampered.
Our lab’s longstanding autoimmunity research program has used animal studies and studies of human twins to identify cell and protein differences in those with and without type 1 diabetes. This work led to the discovery of protein processing defects in the immune cells that cause autoimmune diabetes and other autoimmune diseases. These defects make some populations of disease-causing cells susceptible to death when exposed to certain levels of tumor necrosis factor (TNF), a key signaling protein in the immune system that orchestrates communication between immune cells and controls many of their functions. Based on these findings, the Immunobiology Lab identified a way to permanently reverse type 1 diabetes in mice, a project that is now being testing in human clinical trials. The lab is also seeking to expand these findings to other immune-mediated diseases, such as Crohn’s disease, lupus, and Sjögren’s syndrome.
Type 1 Diabetes Clinical Translational Project
Dr. Faustman and colleagues are undertaking a program of research aimed at developing a curative therapy for human type 1 diabetes. This project consists of several parts:
Studies in Mice:Studies in the non-obese diabetic (NOD) mouse are being conducted to refine and optimize a therapy to eliminate type 1 diabetes in humans. The NOD mice are a model of both type 1 diabetes and Sjögren’s syndrome, an autoimmune disease of the salivary glands.
Refinement of Robotic Machinery for Blood Cell Separation: The lab has developed robotic machinery that can separate populations of white blood cells from a tube of whole blood and measure the concentration of abnormal white blood cells in blood samples from patients with type 1 diabetes and other immune-mediated diseases, including Crohn’s disease, lupus, hypothyroidism, Sjögren’s syndrome, and rheumatoid arthritis. This machinery is being used in our human clinical trials testing a potential treatment for human type 1 diabetes. By enabling us to look at the concentration of specific cells, this machinery can be used to see how well a potential therapy works to eliminate disease-causing cells and can help us identify the optimal drug dose and timing of administration.
Our lab has demonstrated that this blood cell separation machinery improves cell viability, purity and yield compared to standard gradient (Ficoll) methods of blood cell separation. Current efforts at the lab are focused on expanding the capacity and efficiency of this machinery so that it can process more blood samples in a shorter amount of time and thereby support human clinical trials that include greater numbers of patients.
BCG Human Clinical Trial Program:This program is investigating whether vaccination with bacillus Calmette-Guérin (BCG) will eliminate disease-causing T cells in humans with advanced type 1 diabetes. BCG is a generic drug that has been used for over 80 years in different capacities, including vaccination against tuberculosis. Our human clinical studies are testing BCG at different doses and schedules than those currently used. An FDA-approved, Phase I human clinical trial was recently completed, showing the safety of BCG vaccination in type 1 diabetics. A Phase II study is currently being planned.
Generic Drug Screening Program for Autoimmune Disease
The Faustman lab is investigating a screening program to find appropriate generics that can be "recycled" for new clinical indications in autoimmune diseases, including lupus, Crohn's disease, rheumatoid arthritis, scleroderma, multiple sclerosis, and Sjögren’s syndrome.
Cellular Transplantation Program
This research program was created to identify the molecules on donor tissues that cause transplant rejection. Our achievements include successfully modifying donor tissues so that they can be transplanted into small and large animals without use of immunosuppression and applying this technology to diverse tissues (e.g. liver, neurons and muscle). With our laboratory’s discovery of spontaneous end-organ regeneration upon elimination of autoimmune disease, we hope that the need for organ or cell transplant will be eliminated for type 1 diabetes.