The Endocrine Division has a longstanding, comprehensive program of research and training in all aspects of endocrinology, which is undertaken within the cooperating units.

A brief description of the interests of each Unit follows.

 

 

The Diabetes Unit, led by Joseph Avruch, carries out a broad array of laboratory and clinical investigations relevant to the causes and treatments of Type 1 and Type 2 diabetes. The laboratory-based studies focus on understanding the signal transduction mechanisms utilized by insulin, related growth factors and inflammatory cytokines, the regulation of gene expression by insulin and nutrients; the pathogenesis of anti-beta cell autoimmunity, and the biology of pancreatic beta cells relevant to their survival after transplantaion. Clinical research activities focus predominantly on the development, implementation, and evaluation of new therapies for Types 1 and 2 diabetes and the means and consequences of translating new, cost effective therapies into general practice. The Diabetes Clinical Research Center plays a leadership role in several large, NIH-sponsored multicenter studies including the Diabetes Prevention Program, aimed at preventing the development of Type 2 diabetes, the Epidemiology of Diabetes Interventions and Complications Study, a long-term follow-up study of the Diabetes Control and Complications Trial cohort, and the Framingham Heart Study.

Most of the research in the Endocrine Unit, led by Henry Kronenberg, focuses on the regulation of bone and mineral metabolism and bone development. Particular emphasis is placed on parathyroid hormone, parathyroid hormone-related protein, and vitamin D. The work includes both clinical investigation, as exemplified by the Specialized Center for Research in Osteoporosis, funded by NIH, which is conducting a trial of parathyroid hormone therapy for osteoporosis, and fundamental molecular research, such as studies of the mechanisms of action of the PTH/PTHrP receptor. Bone development is studied through the creation of a series of gene "knockout" mice. click for a listing of Endocrine Unit individual research interests

A major interest of the Laboratory of Molecular Endocrinology, led by Joel Habener, is in understanding the roles of transcription factors that determine pancreas development and control the expression of insulin. Factors that stimulate the neogenesis of insulin-producing B-cells and others that are involved in apoptosis of B-cells are under investigation. The general hypothesis is that an interplay of transcription factors regulates the mass of B-cells in the pancreas and that defective functioning of these factors may contribute to the pathogenesis of diabetes mellitus via impaired neogenesis and /or accelerated apoptosis of B-cells.

The research conducted in the Lipid Metabolism Unit, led by Mason Freeman, focuses on the role of lipids and lipoproteins in atherosclerosis. Specifically, the unit is studying macrophage receptors that bind and degrade lipids that engender pro-inflammatory responses in the artery wall. In addition, the mechanism by which high density lipoproteins protect against atherosclerosis is investigated in cell biologic work involving patients with low HDL syndromes such as Tangier disease. Efforts to identify genes involved in cholesterol efflux pathways are included in this work. The Nessel Gene Therapy Center, also directed by the Chief of the Lipid Metabolism Unit, is pursuing work aimed at the development of clinically useful vectors for gene delivery. Diseases for which these vectors are targeted include disorders of lipid metabolism as well as hemophilia and HIV.

Research efforts in the Neuroendocrine Unit, led by Anne Klibanski, include a broad-based program of investigation into the molecular pathogenesis and regulation of human pituitary tumors. Research highlights include the investigation of GnRH receptor biosynthetic defects on human gonadotroph tumors and tumor-specific expression and alternate splicing of mRNA's encoding activin/TGFB receptors in human pituitary tumors. A second major research program within the Unit involves the neuroendocrine regulation of bone mass and body composition. Research highlights include the investigation of rhGH and IFG1 effects on body composition and bone density in patients with GH deficiency and GH resistance states. The effect of endogenous anabolic factors in the pathogenesis of HIV associated wasting syndromes is also under investigation.

The Reproductive Endocrine Unit, led by William Crowley, provides a broad-based clinical and basic investigational program into the scientific basis of reproductive disorders in the human. Active areas of investigation include the roles of the TGF-b family members, activin and inhibin, and their binding protein follistatin, in male and female gonadal function, the role of FSH in male spermatogenesis, neuroendocrine aspects of aging in post-menopausal women, and the genetics and pathophysiology of human reproductive disorders including Kallman's Syndrome and Polycystic Ovary Syndrome. The Unit is supported by one of two NIH-funded National Centers for Infertility Research awarded in this country, a Reproductive Endocrine Sciences Center for core laboratories, and multiple individual investigator NIH grants.