JOSLIN ENDOWMENTS
The Iacocca Foundation is proud to support research at the Joslin Diabetes Center. We’ve funded the following researchers for 2009.

Yingie Liu
Appointed 7/1/08-6/30/09
Postdoctoral fellow in the Vascular Cell Biology Section
Joslin Diabetes Center

Yingie Liu studied the differential effect of protein kinase C (PKC) on insulin signaling pathway in cardiovascular endothelial cells and reports:

Patients with Type1 diabetes have an increased risk of developing atherosclerosis. A major factor is insulin resistance.  We have proposed that insulin has multiple specific actions in the vascular cells that can create anti-atherogenic and atherogenic actions.  IRS-1/2 and the activation of phosphoinositide-3 kinase (PI3K) signaling pathway mediate insulin’s anti-atherogenic actions, while Shc/MAP kinase (MAPK) pathway activation can mediate several atherogenic effects of insulin.  We have proposed that hyperglycemia, dyslipidemia and inflammatory cytokines derived from diabetes will “differentially” inhibit insulin’s activation of PI3K/Akt pathway and its anti-atherogenic effects.

Shane Mayack
Appointed 7/1/08-6/30/09
Postdoctoral fellow in the Islet Transplantation and
Cell Biology Section
Joslin Diabetes Center

Shane Mayack focused on how the loss or functional impairment of tissue-specific stem cells contributes the progressive decline in the body’s ability to maintain homeostatic and injury induced regenerative cell replacement.  He reports:

The ability to isolate osteoblast niche cells has opened a wealth of possibilities for better understanding the cell biological and molecular control of stem cell activity and hematopoiesis.  At Joslin, we established both in vitro and in vivo assays to allow direct assessment of the functional differences between resting and “expanded” HSC (hematopoietic stem cells) niches.  For our Iacocca research plan, we proposed to focus on evaluating the importance of the HSC niche in aging and leukemic transformation with the long-term goal of elucidating their mechanisms of action using genetic perturbation, in vivo transplantation, and in vitro co-culture assays.

Libin Liu
Appointed 7/1/09-6/30/10
Postdoctoral Research Fellow in the Cellular and Molecular Physiology Section
Joslin Diabetes Center

Libin Liu is studying the functional role of macrophage cytokine secretion in obesity-induced inflammation and reports:

Obesity is linked to a chronic, sub-acute state of inflammation documented by the changes in both inflammatory cells and biochemical markers of inflammation.  Macrophages – a type of white blood that ingests foreign material and thus involved in immune response - in adipose tissue has been thought to play a major role during this process, which is mainly acting through cytokines.

We hypothesize that macrophage in obese adipose tissue has a significant requirement for Cpe (carboxypeptidase E) expression corresponding to its cytokines secretion, which is induced by obesity. Macrophage without Cpe may have some dysfunctions of cytokine secretion. Furthermore the obesity phenotype in Cpe-fat mice might be due to Cpe deficient in leukocytes, in particular in adipose tissue leukocytes such as macrophages where we find its expression up regulated so dramatically.

Eystein Husebye
Appointed 8/1/2008-2009
Senior Visiting Scientist in the Immunology Section
Joslin Diabetes Center

Eystein Husebye has been focused on organ-specific autoimmunity in humanized murine models of autoimmune polyendocrine syndrome Type 1 and reports:

Autoimmune diseases are a group of about 80 disorders that can involve almost any tissue or organ.  They affect 5-10% of the population and are one of the top 10 causes of death in women.  Some of these disorders, such as autoimmune thyroid disease and type1 diabetes, are common, while others are rare.  Among the latter is autoimmune polyendocrine syndrome type I (APS-I), a rare, autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene.  Patients gradually develop autoimmune destruction of different endocrine and non-endocrine tissues.  The main components are hypoparathyroidism, primary adrenal failure (Addison’s disease), and chronic candida infections of the skin and mucous membranes.  Up to 20% of patients develop type 1 diabetes.

The generation of Aire-knockout mouse models has been instrumental in elucidating the detailed mechanisms behind central immunological tolerance and how it is broken in autoimmune diseases, but none of the hitherto developed mouse models develop the three main components seen in humans.  To overcome these limitations, the goal of this project has been to create new mouse models with a partially humanized immune system.  The hypothesis was that Aire-knockout mice harboring parts of the human immune system will develop a disease phenotype more similar to that of human patients with APS-I.

Mary K. Iacocca Fellows - Global Impact on Diabetes

The Joslin Diabetes Center is deeply grateful to the Iacocca Foundation for its generous support of the prestigious Iacocca Foundation Fellowships.