Basic science research in biochemistry and immunology provides the foundation that drives the development of new therapies for diabetes and other endocrine diseases. The Department of Diabetes, Endocrinology & Metabolism is conducting a number of important basic science research programs, including those described below:
Scientists at 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. Our scientists are also searching for ways to explore new approaches for inducing immune tolerance in islet transplant recipients using bone marrow stem cells and regulatory T cells. Under the SC-IC, City of Hope currently leads a multicenter clinical study that investigates 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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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 No. 1 cause of death in people with diabetes and accounts for nearly half of all diabetes-related deaths. Our researchers 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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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." AGE formation has also been found to accelerate the aging process and may contribute to the development of Alzheimer's disease. City of Hope researchers have developed novel 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.
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 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.
Ismail Al-Abdullah, Ph.D.: Islet cell isolation.
Kevin Ferreri, Ph.D.: Islet cell differentiation and proliferation
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
Fouad R. Kandeel, M.D., Ph.D.: Clinical islet transplantation, genetic relationships between NIDDM (type 2 diabetes) 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
Hsun Teresa Ku, Ph.D.: In vitro differentiation of human and mouse embryonic stem cells towards pancreatic lineage cells. Identification, purification and characterization of embryonic and adult pancreatic stem/progenitor cells.
Yoko Mullen, M.D., Ph.D.: Human islet cell proliferation and genetic modification; new immune tolerance strategies
Rama Natarajan, Ph.D.: Identification of the molecular mechanisms underlying the accelerated cardiovascular and renal disease observed in diabetic patients, and the role of inflammatory response in islet destruction
Samual Rahbar, M.D., 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
Ivan Todorov, Ph.D.: Islet cell proliferation, differentiation and cryopreservation
Defu Zeng, M.D.: Induction of immune tolerance towards transplanted islets
