Dr. Brian Engelhardt is a Hematologist and Oncologist at Vanderbilt University Medical Center with experience in examining human immunology. My laboratory has focused on investigating immune-mediated complications following allogeneic hematopoietic cell transplantation. I have experience directing and performing multi-investigator, cross-departmental clinical and translational research in humans. Patients undergoing stem cell transplantation are at risk for numerous acute and long-term complications from this procedure including: graft-versus-host disease, delayed immune reconstitution, and metabolic disorders. Post-transplant diabetes mellitus (PTDM) is a common but under-recognized complication after transplant. My data indicate that new-onset diabetes can have a significant impact on the morbidity and mortality of stem cell transplant, and that these metabolic factors are linked to cellular immune processes. Despite the high prevalence, there is a paucity of prospective data on the physiology, immunology, risk factors, and optimized treatment schedules for post-transplant diabetes mellitus, indicating a need for a new direction of research. By studying the physiology and immunology of new-onset diabetes after stem cell transplant, I perform mechanistic studies that uncover new connections between metabolic complications and immune regulation while simultaneously identifying novel targets for intervention. To investigate metabolic complications I use a combination of immunology and endocrine research methods including oral glucose tolerance testing and glucose clamp techniques to measure changes in metabolic function. Currently, I am studying the role of circulating tissue-homing regulatory T cells, Th1 cells and hepatic / peripheral insulin sensitivity in the development of new-onset diabetes after stem cell transplant. Preliminary data from this study indicates that post-transplant diabetes is associated with not only hepatic insulin resistance but also insulin insufficiency, excess glucagon secretion, and changes in the IL-33/ST2 immune signaling pathway. I propose that understanding the immunology and the metabolic abnormalities generating post-transplant diabetes mellitus will promote rapid improvements in the care of allogeneic hematopoietic cell transplant recipients.
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Key: MeSH Term KeywordAdrenal Cortex Hormones Allogeneic Hematopoietic Cell Transplantation Allografts Bilirubin Case-Control Studies Cell Adhesion Molecules Chronic Disease Flow Cytometry Forecasting Graft-vs-Host Disease Humans Hypersensitivity Immunosuppressive Agents Infant, Premature Inflammation Intestinal Mucosa Kaplan-Meier Estimate Leukemia, B-Cell Lymphocytes Lymphoma, Non-Hodgkin Methotrexate Mice Mutation Organ Specificity Post-transplant Diabetes Mellitus Postoperative Complications Proportional Hazards Models Regulatory T cells Skin Stem Cell Transplantation T-Lymphocytes, Regulatory Tennessee Transplantation Conditioning Vidarabine Young Adult