Brian G Engelhardt, M.D.

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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.

Publications

The following timeline graph is generated from all co-authored publications.

1. Reduced-Intensity Conditioning with Fludarabine, Cyclophosphamide, and Rituximab Is Associated with Improved Outcomes Compared with Fludarabine and Busulfan after Allogeneic Stem Cell Transplantation for B Cell Malignancies. Kennedy VE, Savani BN, Greer JP, Kassim AA, Engelhardt BG, Goodman SA, Sengsayadeth S, Chinratanalab W, Jagasia M (2016) Biol Blood Marrow Transplant 22(10): 1801-1807
   › Primary publication · 27377900 (PubMed)
2. How do I manage hyperglycemia/post-transplant diabetes mellitus after allogeneic HSCT. Fuji S, Rovó A, Ohashi K, Griffith M, Einsele H, Kapp M, Mohty M, Majhail NS, Engelhardt BG, Tichelli A, Savani BN (2016) Bone Marrow Transplant 51(8): 1041-9
   › Primary publication · 27042848 (PubMed)
3. Early Th1 immunity promotes immune tolerance and may impair graft-versus-leukemia effect after allogeneic hematopoietic cell transplantation. Engelhardt BG, Paczesny S, Jung DK, Daguindau E, Jagasia M, Savani BN, Chinratanalab W, Cornell RF, Goodman S, Greer JP, Kassim AA, Sengsayadeth S, Yoder SM, Rock MT, Crowe JE (2016) Haematologica 101(5): e204-8
   › Primary publication · 26819055 (PubMed) · PMC5004357 (PubMed Central)
4. Extracorporeal photopheresis as second-line treatment for acute graft-versus-host disease: impact on six-month freedom from treatment failure. Das-Gupta E, Greinix H, Jacobs R, Zhou L, Savani BN, Engelhardt BG, Kassim A, Worel N, Knobler R, Russell N, Jagasia M (2014) Haematologica 99(11): 1746-52
   › Primary publication · 25150260 (PubMed) · PMC4222474 (PubMed Central)
5. Geographic distance is not associated with inferior outcome when using long-term transplant clinic strategy. Ragon BK, Clifton C, Chen H, Savani BN, Engelhardt BG, Kassim AA, Vaughan LA, Lucid C, Jagasia M (2014) Biol Blood Marrow Transplant 20(1): 53-7
   › Primary publication · 24120525 (PubMed)
6. Six-month freedom from treatment failure is an important end point for acute GVHD clinical trials. Sengsayadeth S, Savani BN, Jagasia M, Goodman S, Greer JP, Chen H, Chinratanalab W, Kassim AA, Engelhardt BG (2014) Bone Marrow Transplant 49(2): 236-40
   › Primary publication · 24096824 (PubMed) · PMC3946331 (PubMed Central)
7. Outcomes of autologous or allogeneic stem cell transplantation for non-Hodgkin lymphoma. Reddy NM, Oluwole O, Greer JP, Engelhardt BG, Jagasia MH, Savani BN (2014) Exp Hematol 42(1): 39-45
   › Primary publication · 24096123 (PubMed) · PMC5002948 (PubMed Central)
8. New allergies after cord blood transplantation. Vaughan LA, Vu M, Sengsayadeth S, Lucid C, Clifton C, McCarty K, Hagaman D, Domm J, Kassim A, Chinratanalab W, Goodman S, Greer J, Frangoul H, Engelhardt BG, Jagasia M, Savani BN (2013) Cytotherapy 15(10): 1259-65
   › Primary publication · 23993300 (PubMed)
9. Extracorporeal photopheresis versus anticytokine therapy as a second-line treatment for steroid-refractory acute GVHD: a multicenter comparative analysis. Jagasia M, Greinix H, Robin M, Das-Gupta E, Jacobs R, Savani BN, Engelhardt BG, Kassim A, Worel N, Knobler R, Russell N, Socie G (2013) Biol Blood Marrow Transplant 19(7): 1129-33
   › Primary publication · 23623892 (PubMed)
10. Superior long-term outcome of patients with early transformation of non-Hodgkin lymphoma undergoing stem cell transplantation. Reddy N, Oluwole O, Greer JP, Goodman S, Engelhardt B, Jagasia MH, Savani BN (2012) Clin Lymphoma Myeloma Leuk 12(6): 406-11
    › Primary publication · 22981964 (PubMed) · PMC4845749 (PubMed Central)

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