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The Department of Diabetes, Endocrinology & Metabolism is conducting a number of important basic science research programs, including those described below:
Islet Cell Transplantation
Scientists at the City of Hope are leading collaborative research programs in islet transplantation, islet engineering, and islet immunology. This collaboration has been termed the Southern California Islet Consortium (SC-IC) and currently includes participation from the following institutions: Cedars-Sinai Medical Center, Harbor-UCLA Medical Center, Loma Linda University Medical Center, Southern California Transplantation Institute, St. Vincent Medical Center, The Whittier Institute for Diabetes/Scripps Green Center for Organ and Cell Transplantation and UCLA Center for Health Sciences. In addition to the preparation of clinical-grade islets for transplantation, SC-IC scientists are examining new islet harvesting and proliferation techniques, mechanisms of islet-cell progenitor differentiation, and new procedures for islet transfer. Efforts are also being made to explore new approaches for inducing immune tolerance in islet transplant recipients using bone marrow stem cells and regulatory T cells. The first multi-center clinical study led by the City of Hope under the SC-IC will investigate the safety and efficacy of islet transplantation alone in patients with type 1 diabetes using a unique and glucocorticoid-free immunosuppressive regime.
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Heart and Kidney Complications of Diabetes
Diabetes is the leading cause of kidney failure and a significant risk factor for the development of coronary disease. In fact, heart disease is the leading cause of death in people with diabetes and accounted for half of all diabetes-related deaths in 1990. Researchers at City of Hope are studying mechanisms of atherosclerosis and kidney disease in diabetic animal models and humans. The focus of this research is to develop protective strategies for preventing and reversing these complications.
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Controlling Complications
One mechanism for the development of diabetes complications is the changes in protein and fat structure of body tissues as a result of increased attachment of glucose to these tissue structures, a process known scientifically as the "formation of advanced glycation endproducts" or "AGEs". AGEs formation has also been found to accelerate the aging process and may contribute to the development of Alzheimer's disease. Researchers at the City of Hope have developed novel heterocyclic compounds that inhibit glycation and AGE formation and are currently testing their safety and effectiveness in preventing diabetes complications and delaying the tissue aging process. Some of these compounds can also break existing AGEs and could therefore potentially reverse existing tissue damage induced by diabetes.
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New Molecular Discoveries
City of Hope researchers have discovered the molecular mechanisms underlying the body's main method of metabolizing and destroying cholesterol. This research may open the door for new drug therapies for patients with abnormally high cholesterol levels, atherosclerosis and diabetes. These researchers have also discovered a fat-derived hormone called Androstanol that reverses or halts gene activity in the cell nucleus. The discovery of Androstanol is expected to transform our current understanding of metabolic diseases and aid the development of future therapies.
Thyroid Cancer and Neuroendocrine Tumors
Plans are underway to extend current effort in thyroid cancer and neuroendocrine tumor clinical research. This will advance the use of I-131 and rh-TSH in treatment of differentiated thyroid cancer, I-131 labeled MIBG in treatment of advanced pheochromocytoma, iodocholesterol scanning in diagnosis of the adrenal mass, radiolabeled anti-CEA and radiolabeled somatostatin analogues in treatment of other neuroendocrine tumors, and PET scanning in the diagnosis and management of a variety of endocrine tumors. It is hoped that such research efforts will advance the diagnosis and/or treatment of these endocrine tumors beyond what is currently available.
Current Research Programs Performed by Scientists in the Department of Diabetes, Endocrinology and Metabolism
| Wei Feng, M.D.: |
The use of inhaled insulin preparations in treating type 1 diabetic patients, and the role of new medical treatments of diabetic neuropathy.
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| Kevin Ferreri, Ph.D.: |
Islet cell differentiation and proliferation.
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| Barry Forman, M.D., Ph.D.: |
New metabolic pathways and hormone discoveries for development of potential new therapies for diabetes, elevated cholesterol levels and cancer.
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Fouad Kandeel,
M.D., Ph.D.: |
Clinical islet transplantation, genetic relationships between NIDDM and atherosclerosis in the Hispanic population, effect of cancer treatment on bone metabolism, sexual function post-hematopoietic cell transplantation in patients with hematologic malignancies, treatment of neuroendocrine tumors with radioactive MIBG.
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| Yoko Mullen, M.D., Ph.D.: |
Human islet cell proliferation and genetic modification, and new immune tolerance strategies.
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| Rama Natarajan, Ph.D.: |
Identification of the underlying molecular mechanisms underlying the accelerated cardiovascular and renal disease observed in diabetic patients, and role of inflammatory response in islet destruction.
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| Samual Rahbar, Ph.D.: |
Prevention and reversal of excessive attachment of glucose to proteins and fats (glycation) in body structures that are involved in the development of long-term diabetes complications. |
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| Ivan Todorov, Ph.D.: |
Islet cell proliferation, differentiation and cryopreservation.
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| Defu Zeng, M.D.: |
Induction of immune tolerance towards transplanted islets. |
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Additional Basic Research
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