Dale Greiner, Ph.D. - Investigator Profile
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. 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, our studies in humanized mice have the potential to guide human clinical trials in T1D by determining the mechanisms by which therapeutic approaches such as those based on the new technology of RNAi can act directly on human beta cells and human immune systems in vivo, facilitating the direct translation of these agents into the clinic.
Scientific Interests/Keywords
autoimmune diabetes, Transplantation tolerance, beta cell regeneration, humanized mice
Affiliates
Publications
| PubMedID | Citation |
|---|---|
| 19120266 | King M, Pearson T, Rossini AA, Shultz LD, Greiner DL. Humanized mice for the study of type 1 diabetes and beta cell function. (2008) Ann N Y Acad Sci 1150: 46-53 |
| 18563383 | Pearson T, Shultz LD, Lief J, Burzenski L, Gott B, Chase T, Foreman O, Rossini AA, Bottino R, Trucco M, Greiner DL. A new immunodeficient hyperglycaemic mouse model based on the Ins2Akita mutation for analyses of human islet and beta stem and progenitor cell function. (2008) Diabetologia 51: 1449-56 |
| 18481451 | Pearson T, Greiner DL, Shultz LD. Humanized SCID mouse models for biomedical research. () Curr Top Microbiol Immunol 324: 25-51 |
| 18096436 | King M, Pearson T, Shultz LD, Leif J, Bottino R, Trucco M, Atkinson MA, Wasserfall C, Herold KC, Woodland RT, Schmidt MR, Woda BA, Thompson MJ, Rossini AA, Greiner DL. 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. (2008) Clin Immunol 126: 303-14 |
| 17259968 | Shultz LD, Ishikawa F, Greiner DL. Humanized mice in translational biomedical research. (2007) Nat Rev Immunol 7: 118-30 |
