Research Programs at the MGH Immunobiology Lab
Basic Science Programs
The Immunobiology Laboratory investigates mechanisms used by the immune system to select autoimmune T cells versus normal T cells. The lab is also working to characterize the proteins in splenic stem cells from the mouse and the human; to explore the potential role of the spleen as a reservoir for adult stem cells that contribute to the restoration of glycemic control in diabetes once the autoimmune disease has been eliminated; and to identify alternative compounds for killing naive T cells in NOD mice or diabetic human lymphocytes.
Autoimmune Programs
Dr. Faustman's 15-year research program on autoimmunity has utilized comparisons of proteins and cells between affected and unaffected identical human twins or disease disparate inbred NOD mice with autoimmune diabetes. This has led to the discovery of an overabundance of naive T cells, defects in antigen presenting cells, defects in MHC class I presentation of self-peptides, altered NFkB activation/regulation and hampered resistance to cytokine induced apoptosis. These protein processing defects are specific to the diseased cell of the affected cohort regardless of genotype. These phenotypes have successfully been used as therapies to permanently reverse disease in spontaneously diabetic mice. The long-term follow-up of these mice reveals restored normoglycemia is due to the restoration of pancreatic insulin secretion with islet reappearance due to presumed regeneration or rescue.
Nathan/Faustman 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 three major parts:
Studies in the NOD Mouse: Further studies in the NOD mouse are being conducted to refine and optimize a therapy to eliminate type 1 diabetes in humans.
Bioassay Development and Automation: A bioassay (blood test) is being developed and automated to measure the concentration of abnormal white blood cells in blood samples from patients with type 1 diabetes. Once the assay is developed in the next 12 to 18 months, the Faustman lab will be able to use this blood test to select participants for the human trial (by looking at their blood and seeing if a treatable defect is present) and to see how well the potential therapy works to eliminate the abnormal, disease-causing cells. It will also be used to establish the best dose and timing of the drug.
BCG Human Clinical Trial: This Phase I human clinical trial will enroll type 1 diabetic volunteers to determine whether treatment with bacillus Calmette-Guerin (BCG) vaccination can eliminate the abnormal white blood cells in patients with type 1 diabetes and to find the optimal dose and timing of BCG administration. This trial is FDA approved and will be led by Dr. David Nathan.
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 Sjogren's syndrome.
Cellular Transplantation Program
Dr. Faustman created this research program to identify the target molecules on donor tissues which trigger T cell recognition and cause transplant rejection. Achievements include: the successful application of designer donor tissues (donor antigen modification) to transplant foreign cells without immunosuppression into small and large animal models; the first application of this technology to diverse tissues (e.g. liver, neurons and muscle); and elucidation of basic mechanisms of active tolerance which sustains graft acceptance as it relates to donor antigen modifications. This technology has started a pathway to commercialization and is in Phase I-II clinical trials for multiple human diseases including Parkinson's disease. This technology and patent is the central for expansion of animal cloning methods to prevent host recognition by modification of cells or animals such as pigs prior to transplantation.
Human Islet Cell Transplantation Program
Techniques for islet isolation and immunological manipulation were translated to clinical practice with the creation of the first islet cell transplantation program for diabetes in New England in cooperation with Dr. David Nathan. The Immunobiology Laboratory under Dr. Faustman designed and implemented an automated process to transplant islets into humans, a process originally developed from research involving Dr. Faustman's thesis work at Washington University. Critical collaborations with regional and national organ banks were established to ensure an adequate pancreas supply
Learn more about diabetes research at Mass General. Visit the MGH Diabetes Clinical Research Center's web site.
