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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 Oral insulin does not prevent insulin-dependent diabetes mellitus in BB rats.
Academic Article Role of natural killer cells on engraftment of human lymphoid cells and on metastasis of human T-lymphoblastoid leukemia cells in C57BL/6J-scid mice and in C57BL/6J-scid bg mice.
Academic Article Improved engraftment of human cord blood stem cells in NOD/LtSz-scid/scid mice after irradiation or multiple-day injections into unirradiated recipients.
Academic Article Enhanced human CD4+ T cell engraftment in beta2-microglobulin-deficient NOD-scid mice.
Academic Article CD8+ T lymphocytes are not required for murine resistance to human filarial parasites.
Academic Article The T cell marker RT6 in a rat model of autoimmune diabetes.
Academic Article SCID mouse models of human stem cell engraftment.
Academic Article HIV-1 infectivity of human T cells in a human/murine chimeric fetal thymic organ culture system.
Academic Article Animal models for immunodeficiency diseases.
Academic Article Induction of islet transplantation tolerance using donor specific transfusion and anti-CD154 monoclonal antibody.
Academic Article Growth of the human filarial parasite Brugia malayi in mice lacking major histocompatibility complex class II antigen expression.
Academic Article Regulation of human cell engraftment and development of EBV-related lymphoproliferative disorders in Hu-PBL-scid mice.
Academic Article Variables to predict engraftment of umbilical cord blood into immunodeficient mice: usefulness of the non-obese diabetic--severe combined immunodeficient assay.
Academic Article Blockade of CD40-CD154 interferes with human T cell engraftment in scid mice.
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 Induction of immunologic tolerance for transplantation.
Academic Article Genetic separation of the transplantation tolerance and autoimmune phenotypes in NOD mice.
Academic Article Comparative mapping of rat Iddm4 to segments on HSA7 and MMU6.
Academic Article Insulin dependent diabetes mellitus hypothesis of autoimmunity.
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 Effect of ex vivo cytokine treatment on human cord blood engraftment in NOD-scid mice.
Academic Article beta2 microglobulin-deficient (B2m(null)) NOD/SCID mice are excellent recipients for studying human stem cell function.
Academic Article Humanized NOD/LtSz-scid IL2 receptor common gamma chain knockout mice in diabetes research.
Academic Article Translating data from animal models into methods for preventing human autoimmune diabetes mellitus: caveat emptor and primum non nocere.
Academic Article Creation of "humanized" mice to study human immunity.
Academic Article Non-obese diabetic-recombination activating gene-1 (NOD-Rag1 null) interleukin (IL)-2 receptor common gamma chain (IL2r gamma null) null mice: a radioresistant model for human lymphohaematopoietic engraftment.
Academic Article Closing the circle between the bedside and the bench: Toll-like receptors in models of virally induced diabetes.
Academic Article Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complex.
Academic Article Infection with viruses from several families triggers autoimmune diabetes in LEW*1WR1 rats: prevention of diabetes by maternal immunization.
Academic Article Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NOD-scid IL2rgammanull mice.
Academic Article AATF mediates an antiapoptotic effect of the unfolded protein response through transcriptional regulation of AKT1.
Academic Article Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation.
Academic Article Humanized mouse models to study human diseases.
Academic Article Islet cell transplantation tolerance.
Academic Article Prevention of "Humanized" diabetogenic CD8 T-cell responses in HLA-transgenic NOD mice by a multipeptide coupled-cell approach.
Academic Article Human islet cell MORF/cMORF pretargeting in a xenogeneic murine transplant model.
Academic Article The pathogenesis of autoimmune diabetes mellitus.
Academic Article Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2r? null mice is enhanced by transgenic expression of membrane-bound human SCF.
Academic Article Pretargeting vs. direct targeting of human betalox5 islet cells subcutaneously implanted in mice using an anti-human islet cell antibody.
Academic Article Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice.
Academic Article Thioredoxin-interacting protein mediates ER stress-induced ? cell death through initiation of the inflammasome.
Academic Article Humanized mice for immune system investigation: progress, promise and challenges.
Academic Article Survival of Onchocerca volvulus in nodules implanted in immunodeficient rodents.
Academic Article GLI1 regulates a novel neuropilin-2/a6?1 integrin based autocrine pathway that contributes to breast cancer initiation.
Academic Article Durable knockdown and protection from HIV transmission in humanized mice treated with gel-formulated CD4 aptamer-siRNA chimeras.
Academic Article Regulation of human short-term repopulating cell (STRC) engraftment in NOD/SCID mice by host CD122+ cells.
Academic Article Alloimmune injury and rejection of human skin grafts on human peripheral blood lymphocyte-reconstituted non-obese diabetic severe combined immunodeficient beta2-microglobulin-null mice.
Academic Article NOD/LtSz-Rag1nullPfpnull mice: a new model system with increased levels of human peripheral leukocyte and hematopoietic stem-cell engraftment.
Academic Article High levels of human peripheral blood mononuclear cell engraftment and enhanced susceptibility to human immunodeficiency virus type 1 infection in NOD/LtSz-scid/scid mice.
Academic Article Emv30null NOD-scid mice. An improved host for adoptive transfer of autoimmune diabetes and growth of human lymphohematopoietic cells.
Academic Article CD4+ T-lymphocytes are not required for murine resistance to the human filarial parasite, Brugia malayi.
Academic Article Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice.
Academic Article Rejection of human islets and human HLA-A2.1 transgenic mouse islets by alloreactive human lymphocytes in immunodeficient NOD-scid and NOD-Rag1(null)Prf1(null) mice.
Academic Article Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells.
Academic Article The immunodeficient scid mouse as a model for human lymphatic filariasis.
Academic Article Rapid quantification of naive alloreactive T cells by TNF-alpha production and correlation with allograft rejection in mice.
Academic Article Humanized mice in translational biomedical research.
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 A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in the IL-2 receptor gamma chain gene.
Academic Article Humanized SCID mouse models for biomedical research.
Academic Article A new immunodeficient hyperglycaemic mouse model based on the Ins2Akita mutation for analyses of human islet and beta stem and progenitor cell function.
Academic Article Expanded CD34+ human umbilical cord blood cells generate multiple lymphohematopoietic lineages in NOD-scid IL2rgamma(null) mice.
Academic Article T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice.
Academic Article Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice.
Academic Article Viral infection: a potent barrier to transplantation tolerance.
Academic Article Humanized mice for the study of type 1 diabetes and beta cell function.
Academic Article Role of innate immunity in transplantation tolerance.
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 Development of novel major histocompatibility complex class I and class II-deficient NOD-SCID IL2R gamma chain knockout mice for modeling human xenogeneic graft-versus-host disease.
Academic Article Targeted delivery of small interfering RNA to human dendritic cells to suppress dengue virus infection and associated proinflammatory cytokine production.
Academic Article NOD-scid IL2rgamma(null) mouse model of human skin transplantation and allograft rejection.
Academic Article Preparation of (111)In-DTPA morpholino oligomer for low abdominal accumulation.
Academic Article Human immune system development and rejection of human islet allografts in spontaneously diabetic NOD-Rag1null IL2rgammanull Ins2Akita mice.
Academic Article Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats.
Academic Article Humanized nonobese diabetic-scid IL2rgammanull mice are susceptible to lethal Salmonella Typhi infection.
Academic Article Hyperglycemia-induced proliferation of adult human beta cells engrafted into spontaneously diabetic immunodeficient NOD-Rag1null IL2r?null Ins2Akita mice.
Academic Article Targeted disruption of the CCR5 gene in human hematopoietic stem cells stimulated by peptide nucleic acids.
Academic Article T-cell activation and transplantation tolerance.
Academic Article Humanized mice as a preclinical tool for infectious disease and biomedical research.
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 Systemic delivery of triplex-forming PNA and donor DNA by nanoparticles mediates site-specific genome editing of human hematopoietic cells in vivo.
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 Generation of islet-like cells from mouse gall bladder by direct ex vivo reprogramming.
Academic Article Humanized mice for the study of infectious diseases.
Academic Article Regulatory T cell control of autoimmune destruction of beta cells in the BB rat.
Academic Article Improved engraftment of human spleen cells in NOD/LtSz-scid/scid mice as compared with C.B-17-scid/scid mice.
Academic Article B lymphocytes are not required for murine resistance to the human filarial parasite, Brugia malayi.
Academic Article A selective culture system for generating terminal deoxynucleotidyl transferase-positive lymphoid precursor cells in vitro. IV. Properties and developmental relationships of the lymphoid cells in the adherent and nonadherent compartments of the culture.
Academic Article Human autoimmune diabetes mellitus: lessons from BB rats and NOD mice--Caveat emptor.
Academic Article High stimulatory activity of dendritic cells from diabetes-prone BioBreeding/Worcester rats exposed to macrophage-derived factors.
Concept Humans
Concept Chromosomes, Human, Pair 4
Concept Herpesvirus 4, Human
Concept Enterovirus B, Human
Concept Chromosomes, Human, Pair 13
Academic Article Regulated splicing of the a6 integrin cytoplasmic domain determines the fate of breast cancer stem cells.
Academic Article Overcoming current limitations in humanized mouse research.
Academic Article Comparison between two labeled agents in mice using a coinjection-ratio approach in contrast to a conventional group approach.
Academic Article Engrafted human cells generate adaptive immune responses to Mycobacterium bovis BCG infection in humanized mice.
Academic Article Improved function and proliferation of adult human beta cells engrafted in diabetic immunodeficient NOD-scid IL2r?(null) mice treated with alogliptin.
Academic Article c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells.
Academic Article An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia.
Academic Article NOD-scidIl2rg (tm1Wjl) and NOD-Rag1 (null) Il2rg (tm1Wjl) : a model for stromal cell-tumor cell interaction for human colon cancer.
Academic Article Subcapsular transplantation of tissue in the kidney.
Academic Article Human cancer growth and therapy in immunodeficient mouse models.
Academic Article Viral infection of engrafted human islets leads to diabetes.
Academic Article A laminin 511 matrix is regulated by TAZ and functions as the ligand for the a6B?1 integrin to sustain breast cancer stem cells.
Academic Article Generation of improved humanized mouse models for human infectious diseases.
Academic Article GABA promotes human ?-cell proliferation and modulates glucose homeostasis.
Academic Article Inhibition of bromodomain proteins for the treatment of human diffuse large B-cell lymphoma.
Academic Article Generation of functional human pancreatic ? cells in vitro.
Academic Article Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice.
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 Extensive double humanization of both liver and hematopoiesis in FRGN mice.
Academic Article Novel Observations From Next-Generation RNA Sequencing of Highly Purified Human Adult and Fetal Islet Cell Subsets.
Academic Article Efficient generation of NKX6-1+ pancreatic progenitors from multiple human pluripotent stem cell lines.
Academic Article IMP3 promotes stem-like properties in triple-negative breast cancer by regulating SLUG.
Academic Article Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates.
Academic Article Lixisenatide accelerates restoration of normoglycemia and improves human beta-cell function and survival in diabetic immunodeficient NOD-scid IL-2rg(null) RIP-DTR mice engrafted with human islets.
Academic Article Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection.
Academic Article Efficient and Targeted Transduction of Nonhuman Primate Liver With Systemically Delivered Optimized AAV3B Vectors.
Academic Article P-Rex1 Promotes Resistance to VEGF/VEGFR-Targeted Therapy in Prostate Cancer.
Academic Article Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic ?-cell function via glycogen synthase kinase-3?.
Academic Article Humanized Mouse Models for Transplant Immunology.
Academic Article Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates.
Academic Article Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice.
Academic Article Corrigendum: Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice.
Academic Article Stress-impaired transcription factor expression and insulin secretion in transplanted human islets.
Academic Article Generation of Immunodeficient Mice Bearing Human Immune Systems by the Engraftment of Hematopoietic Stem Cells.
Academic Article Genetically modified human CD4(+) T cells can be evaluated in?vivo without lethal graft-versus-host disease.
Academic Article A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours.
Academic Article Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I.
Academic Article Humanized mouse model of mast cell-mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis.
Academic Article Distinct Differences on Neointima Formation in Immunodeficient and Humanized Mice after Carotid or Femoral Arterial Injury.
Academic Article In vivo correction of anaemia in ?-thalassemic mice by ?PNA-mediated gene editing with nanoparticle delivery.
Academic Article Humanized Mouse Models of Clinical Disease.
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 Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human?primates.
Academic Article mRNA-mediated glycoengineering ameliorates deficient homing of human stem cell-derived hematopoietic progenitors.
Academic Article Possible type 1 diabetes risk prediction: Using ultrasound imaging to assess pancreas inflammation in the inducible autoimmune diabetes BBDR model.
Academic Article Age-dependent human ? cell proliferation induced by glucagon-like peptide 1 and calcineurin signaling.
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 Lack of acute xenogeneic graft- versus-host disease, but retention of T-cell function following engraftment of human peripheral blood mononuclear cells in NSG mice deficient in MHC class I and II expression.
Academic Article Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy.
Academic Article Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic ? Cells for In?Vitro and In?Vivo Analysis.
Academic Article Ectopic high endothelial venules in pancreatic ductal adenocarcinoma: A unique site for targeted delivery.
Academic Article Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics.
Academic Article Survival Advantage of Both Human Hepatocyte Xenografts and Genome-Edited Hepatocytes for Treatment of a-1 Antitrypsin Deficiency.
Academic Article Human Anti-HIV-1 gp120 Monoclonal Antibodies with Neutralizing Activity Cloned from Humanized Mice Infected with HIV-1.
Academic Article Addressing hypersexuality in Alzheimer's disease.
Academic Article Humanized mouse models of immunological diseases and precision medicine.
Academic Article Long-term implant fibrosis prevention in rodents and non-human primates using crystallized drug formulations.
Academic Article AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice.
Academic Article Genome-wide Analysis of Salmonella enterica serovar Typhi in Humanized Mice Reveals Key Virulence Features.
Academic Article Recovery of viable endocrine-specific cells and transcriptomes from human pancreatic islet-engrafted mice.
Academic Article Tacrolimus- and sirolimus-induced human ? cell dysfunction is reversible and preventable.
Academic Article Proteomic and Transcriptional Profiles of Human Stem Cell-Derived ? Cells Following Enteroviral Challenge.
Academic Article A retrievable implant for the long-term encapsulation and survival of therapeutic xenogeneic cells.
Academic Article Dapagliflozin Does Not Directly Affect Human a or ? Cells.
Academic Article Modeling Type 1 Diabetes In?Vitro Using Human Pluripotent Stem Cells.
Academic Article Prostaglandin E2 stimulates cAMP signaling and resensitizes human leukemia cells to glucocorticoid-induced cell death.
Academic Article Author Correction: Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates.
Academic Article Grafting of in vitro cultured melanocytes onto laser-ablated lesions in vitiligo.
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 Enhanced development of functional human NK cells in NOD-scid-IL2rgnull mice expressing human IL15.
Academic Article Humanized mouse models for immuno-oncology research.
Academic Article NOD-scid IL2r?null mice lacking TLR4 support human immune system development and the study of human-specific innate immunity.
Academic Article Simultaneous evaluation of treatment efficacy and toxicity for bispecific T-cell engager therapeutics in a humanized mouse model.
Academic Article Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response.
Academic Article Genetic risk converges on regulatory networks mediating early type 2 diabetes.
Academic Article Nuclear factor kappa B-dependent persistence of Salmonella Typhi and Paratyphi in human macrophages.
Academic Article Human insulin as both antigen and protector in type 1 diabetes.
Academic Article Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners.
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