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Academic Background

Dale Greiner is currently Professor of Molecular Medicine at the University of Massachusetts Medical School. His research focuses on three areas: transplantation, autoimmunity, and the use of humanized mice to study human diseases and infections. Dr. Greiner graduated from the University of Iowa with a Bachelor of Science degree and Medical Technology degree in 1974 and with a Doctor of Philosophy degree in 1978. He did postdoctoral fellowships at the University of Pittsburgh and at the University of Connecticut Health Center in Farmington, CT. He was appointed Assistant Professor at UConn in 1983, Associate Professor in 1989, joined the Department of Medicine at the University of Massachusetts as Professor in 1991 and abecame a Professor od Molecular Medicine in 2010. He became Co-Director with Dr. David Harlan of the Diabetes Center of Excellence in 2010 and the Dr. Eileen L. Berman and Stanley I. Berman Foundation Chair in Biomedical Research Professor in 2013.

To date, Dr. Greiner has co-authored more than 300 publications. He has served as a member of the editorial board of Diabetes, and as a regular member of the National Institutes of Health Immunology Sciences Study Section and the Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section. He has served as chair of the Veterans Administration Immunology Review Subcommittee B and has served as chair of many ad hoc NIH and JDRF study sections. He has also served as Chair of the Medical Science Review Committee for the Juvenile Diabetes Research Foundation, International, Chairman of the American Diabetes Association Scientific Sessions Committee, Program Chair of the American Diabetes Association Council on Immunology, Immunogenetics and Transplantation, and Council Chair, American Diabetes Association Council on Immunology, Immunogenetics and Transplantation.

Dr. Greiner has received numerous awards for his research, including the A.J. Julian Scholarship for Academic Excellence, the Basil O'Connor Scholar Research Award from the March of Dimes, and the Kayla and Gerald Grodsky and David Rumbough Awards from the Juvenile Diabetes Research Foundation, Int.   

Transplantation tolerance and autoimmune diabetes

Our major area of investigation is to understand the etiology and pathogenesis of autoimmune type 1 diabetes mellitus (T1D). Our approach focuses on two main areas, the understanding of the pathogenesis of type 1 diabetes so as to formulate means to prevent or reverse the disease, and the cure of those who are diabetic by induction of transplantation tolerance to islets of Langerhans. Over 25 years ago, we and others accomplished these goals in spontaneously diabetic mouse and rat models of T1D, but these accomplishments have not yet been successfully translated to humans. We believe there are two major obstacles that prevent the achievement of these goals in humans: 1) Lack of understanding of the biology of how human insulin-secreting beta cells die during the development of T1D. 2) Lack of understanding of how a human immune system mediates the destruction of human beta cells in vivo. Our laboratory is focusing on the development of “humanized” mice to study human T1D in collaboration with Dr. Leonard Shultz at The Jackson Laboratory. We have developed unique strains of mice that can be engrafted with functional human cells and tissues, including human islets and human immune systems. We are now using these mice to understand how human beta cells resist killing by a human autoimmune system in vivo, how human beta cells replicate and regenerate in vivo, how human autoreactive cells develop in a human diabetes-susceptible immune system, and how a human immune system targets and kills beta cells in vivo. These approaches are allowing us to understand and dissect mechanisms important in human T1D that cannot be studied directly in humans. Moreover, because these mice readily accept human cells and tissues, we are now using them to study human regenerative medicine, immunity, human-specific infectious agents and cancer. Our studies in humanized mice have the potential to guide human clinical trials by determining the mechanisms by which therapeutic approaches such as those based on the new technology of RNAi can act directly on human immune systems, islets, and cancers in vivo, facilitating the direct translation of these agents into the clinic.

One or more keywords matched the following items that are connected to Greiner, Dale
Item TypeName
Academic Article Cytokine gene expression in islets and thyroids of BB rats. IFN-gamma and IL-12p40 mRNA increase with age in both diabetic and insulin-treated nondiabetic BB rats.
Academic Article Oral insulin does not prevent insulin-dependent diabetes mellitus in BB rats.
Academic Article Induction of insulin-dependent diabetes mellitus in PVG.RT1u rats.
Academic Article The T cell marker RT6 in a rat model of autoimmune diabetes.
Academic Article Effects of HgCl2 on the expression of autoimmune responses and disease in diabetes-prone (DP) BB rats.
Academic Article High frequency apoptosis of recent thymic emigrants in the liver of lymphopenic diabetes-prone BioBreeding rats.
Academic Article Induction of immunological tolerance to islet allografts.
Academic Article Induction of islet transplantation tolerance using donor specific transfusion and anti-CD154 monoclonal antibody.
Academic Article Recapitulation of normal and abnormal BioBreeding rat T cell development in adult thymus organ culture.
Academic Article NOD mice have a generalized defect in their response to transplantation tolerance induction.
Academic Article Diabetes-prone and diabetes-resistant BB rats share a common major diabetes susceptibility locus, iddm4: additional evidence for a "universal autoimmunity locus" on rat chromosome 4.
Academic Article The rat T-cell surface protein RT6 is associated with src family tyrosine kinases and generates an activation signal.
Academic Article The BB/Wor rat and the balance hypothesis of autoimmunity.
Academic Article Abnormalities in the export and fate of recent thymic emigrants in diabetes-prone BB/W rats.
Academic Article Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes.
Academic Article Dietary cow's milk protein does not alter the frequency of diabetes in the BB rat.
Academic Article Altered expression of diabetes in BB/Wor rats by exposure to viral pathogens.
Academic Article NOD congenic mice genetically protected from autoimmune diabetes remain resistant to transplantation tolerance induction.
Academic Article Induction of tolerance for islet transplantation for type 1 diabetes.
Academic Article Non-major histocompatibility complex-linked diabetes susceptibility loci on chromosomes 4 and 13 in a backcross of the DP-BB/Wor rat to the WF rat.
Academic Article Comparative mapping of rat Iddm4 to segments on HSA7 and MMU6.
Academic Article Intravital dye-labeled diabetogenic rat T cells retain dye, home to the pancreas, and induce diabetes.
Academic Article Islet allograft survival induced by costimulation blockade in NOD mice is controlled by allelic variants of Idd3.
Academic Article Insulin dependent diabetes mellitus hypothesis of autoimmunity.
Academic Article The rat diabetes susceptibility locus Iddm4 and at least one additional gene are required for autoimmune diabetes induced by viral infection.
Academic Article Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in a mouse model of type I diabetes.
Academic Article Diabetes prone BB rats are severely deficient in natural killer T cells.
Academic Article NOD/LtSz-Rag1null mice: an immunodeficient and radioresistant model for engraftment of human hematolymphoid cells, HIV infection, and adoptive transfer of NOD mouse diabetogenic T cells.
Academic Article Costimulation and autoimmune diabetes in BB rats.
Academic Article Partial versus full allogeneic hemopoietic chimerization is a preferential means to inhibit type 1 diabetes as the latter induces generalized immunosuppression.
Academic Article TLR9-signaling pathways are involved in Kilham rat virus-induced autoimmune diabetes in the biobreeding diabetes-resistant rat.
Academic Article Fetal thymi from diabetes-prone but not diabetes-resistant BB/Wor rats fail to generate mature ART2+ T-cells in organ culture.
Academic Article BB rat thymocytes cultured in the presence of islets lose their ability to transfer autoimmune diabetes.
Academic Article Translating data from animal models into methods for preventing human autoimmune diabetes mellitus: caveat emptor and primum non nocere.
Academic Article Idd loci synergize to prolong islet allograft survival induced by costimulation blockade in NOD mice.
Academic Article Closing the circle between the bedside and the bench: Toll-like receptors in models of virally induced diabetes.
Academic Article Virus-induced autoimmune diabetes in the LEW.1WR1 rat requires Iddm14 and a genetic locus proximal to the major histocompatibility complex.
Academic Article Levels of Art2+ cells but not soluble Art2 protein correlate with expression of autoimmune diabetes in the BB rat.
Academic Article Infection with viruses from several families triggers autoimmune diabetes in LEW*1WR1 rats: prevention of diabetes by maternal immunization.
Academic Article Cardioprotection with postconditioning: loss of efficacy in murine models of type-2 and type-1 diabetes.
Academic Article Defects in the thymic epithelial stroma of diabetes prone BB rats.
Academic Article Prevention of "Humanized" diabetogenic CD8 T-cell responses in HLA-transgenic NOD mice by a multipeptide coupled-cell approach.
Academic Article The pathogenesis of autoimmune diabetes mellitus.
Academic Article Prevention of type 1 diabetes in the rat with an allele-specific anti-T-cell receptor antibody: V?13 as a therapeutic target and biomarker.
Academic Article T-lymphocyte requirement for diabetes in RT6-depleted diabetes-resistant BB rats.
Academic Article The iddm4 locus segregates with diabetes susceptibility in congenic WF.iddm4 rats.
Academic Article Infections that induce autoimmune diabetes in BBDR rats modulate CD4+CD25+ T cell populations.
Academic Article Absence of the RT-6 T cell subset in diabetes-prone BB/W rats.
Academic Article Genetic disassociation of autoimmunity and resistance to costimulation blockade-induced transplantation tolerance in nonobese diabetic mice.
Academic Article Insulin treatment prevents diabetes mellitus but not thyroiditis in RT6-depleted diabetes resistant BB/Wor rats.
Academic Article Emv30null NOD-scid mice. An improved host for adoptive transfer of autoimmune diabetes and growth of human lymphohematopoietic cells.
Academic Article Adoptive transfer of autoimmune diabetes mellitus to athymic rats: synergy of CD4+ and CD8+ T cells and prevention by RT6+ T cells.
Academic Article Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice.
Academic Article Evidence that intrathymic islet transplantation does not prevent diabetes or subsequent islet graft destruction in RT6-depleted, diabetes-resistant BioBreeding/Worcester rats.
Academic Article Deficiencies in gut NK cell number and function precede diabetes onset in BB rats.
Academic Article Prolonged survival of neonatal porcine islet xenografts in mice treated with a donor-specific transfusion and anti-CD154 antibody.
Academic Article Rat models of type 1 diabetes: genetics, environment, and autoimmunity.
Academic Article Autoimmune diabetes and resistance to xenograft transplantation tolerance in NOD mice.
Academic Article A regulatory CD4+ T cell subset in the BB rat model of autoimmune diabetes expresses neither CD25 nor Foxp3.
Academic Article Development of new-generation HU-PBMC-NOD/SCID mice to study human islet alloreactivity.
Academic Article Diabetes research in jeopardy: the extinction of clinical diabetes researchers.
Academic Article Refinement of the Iddm4 diabetes susceptibility locus reveals TCRVbeta4 as a candidate gene.
Academic Article Humanized mice for the study of type 1 diabetes and beta cell function.
Academic Article Analysis of the rat Iddm14 diabetes susceptibility locus in multiple rat strains: identification of a susceptibility haplotype in the Tcrb-V locus.
Academic Article Failure of alpha-galactosylceramide to prevent diabetes in virus-inducible models of type 1 diabetes in the rat.
Academic Article Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats.
Academic Article Haptoglobin as an early serum biomarker of virus-induced autoimmune type 1 diabetes in biobreeding diabetes resistant and LEW1.WR1 rats.
Academic Article Prevention of diabetes in BB/Wor rat by single transfusion of spleen cells. Parameters that affect degree of protection.
Academic Article Humanized mice for the study of type 1 and type 2 diabetes.
Academic Article Advancing animal models of human type 1 diabetes by engraftment of functional human tissues in immunodeficient mice.
Academic Article Islet-specific CTL cloned from a type 1 diabetes patient cause beta-cell destruction after engraftment into HLA-A2 transgenic NOD/scid/IL2RG null mice.
Academic Article Regulatory T cell control of autoimmune destruction of beta cells in the BB rat.
Academic Article DR-BB rat thymus contains thymocyte populations predisposed to autoreactivity.
Academic Article Human autoimmune diabetes mellitus: lessons from BB rats and NOD mice--Caveat emptor.
Academic Article Multiple low-dose streptozocin-induced diabetes in NOD-scid/scid mice in the absence of functional lymphocytes.
Academic Article Major histocompatibility complex class I-deficient NOD-B2mnull mice are diabetes and insulitis resistant.
Concept Diabetes Mellitus, Type 2
Concept Diabetes Mellitus, Type 1
Academic Article Salicylate prevents virus-induced type 1 diabetes in the BBDR rat.
Academic Article Blockade of the programmed death-1 (PD1) pathway undermines potent genetic protection from type 1 diabetes.
Academic Article Viral infection of engrafted human islets leads to diabetes.
Academic Article Generation of ? cell-specific human cytotoxic T cells by lentiviral transduction and their survival in immunodeficient human leucocyte antigen-transgenic mice.
Academic Article The Presence and Preferential Activation of Regulatory T Cells Diminish Adoptive Transfer of Autoimmune Diabetes by Polyclonal Nonobese Diabetic (NOD) T Cell Effectors into NSG versus NOD-scid Mice.
Academic Article Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic ?-cell function via glycogen synthase kinase-3?.
Academic Article Genetic ablation of lymphocytes and cytokine signaling in nonobese diabetic mice prevents diet-induced obesity and insulin resistance.
Academic Article Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice.
Academic Article Impaired osteogenesis of T1DM bone marrow-derived stromal cells and periosteum-derived cells and their differential in-vitro responses to growth factor rescue.
Academic Article Possible type 1 diabetes risk prediction: Using ultrasound imaging to assess pancreas inflammation in the inducible autoimmune diabetes BBDR model.
Academic Article a Cell Function and Gene Expression Are Compromised in Type 1 Diabetes.
Academic Article Report of the Key Opinion Leaders Meeting on Stem Cell-derived Beta Cells.
Academic Article Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic ? Cells for In?Vitro and In?Vivo Analysis.
Academic Article Modeling Type 1 Diabetes In?Vitro Using Human Pluripotent Stem Cells.
Academic Article A therapeutic convection-enhanced macroencapsulation device for enhancing ? cell viability and insulin secretion.
Academic Article Modeling human T1D-associated autoimmune processes.
Academic Article An Early Islet Transcriptional Signature Is Associated With Local Inflammation in Autoimmune Diabetes.
Academic Article I-Ag7 ?56/57 polymorphisms regulate non-cognate negative selection to CD4+ T cell orchestrators of type 1 diabetes.
Academic Article Genetic risk converges on regulatory networks mediating early type 2 diabetes.
Academic Article Human insulin as both antigen and protector in type 1 diabetes.
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  • Diabetes Mellitus Type 2