Professor of Physiology
Dr. North attended the Australian National University where he majored in chemistry and zoology. He graduated with a B.Sc. in 1964. He completed a B.Sc. Honours (M.S. equivalent) in comparative physiology at the University of Melbourne in 1966 and then went on to complete a Ph.D. in physiology and a Ph.D. in biochemistry at the University of Queensland in 1973. From 1968 through 1972, he was a part-time lecturer at the Queensland Institute of Technology, where he organized and taught a course in industrial chemistry and lectured in biochemistry. From February 1973 to August 1974, he was a Visiting Associate in the Department of Physiology at the Mount Sinai School of Medicine, New York.
Dr. North was also a Research Associate with Dr. Heinz Valtin, Department of Physiology, Dartmouth Medical School, Hanover, NH. Neurohypophysial peptide hormone biosynthesis, storage, and release. Production of peptide hormones by small cell tumors. 1974-1975.
Acting Assistant Professor of Physiology, Dartmouth Medical School, Hanover, NH. 1975-1977.
Assistant Professor of Physiology, Dartmouth Medical School, Hanover, NH. 1977-1980.
Associate Professor of Physiology, Dartmouth Medical School, Hanover, NH. 1980 to 1988.
Professor of Physiology, Dartmouth Medical School, Hanover, NH. 1988 to present.
Dr. North joined the Dartmouth Medical School faculty in 1974 and was a recipient of a Research Career Development Award from 1979 to 1984. He is the director of the Endocrine Training Program and the director of the Protein Analysis Unit at Dartmouth. The studies conducted in this laboratory are centered on the expression of vasopressin and oxytocin genes, and on the post-transcriptional and post-translational generation of vasopressin, oxytocin, and neurophysins by hypothalamic neurons, small cell carcinoma and breast cancer. Vasopressin and oxytocin are classically recognized as hormones of antidiuresis, of blood pressure regulation, of parturition, and of milk-ejection. However, they are now also known to play key roles in learning behavior, blood clotting, corpus luteal function, and cell mitogenesis. Neurophysins are 10,000-dalton proteins that represent major portions of the biosynthetic precursors for vasopressin and oxytocin. The steps involved in post-translational processing are examined using in vivo and in vitro methods of radiolabel incorporation into proteins, a high-performance chromatographic procedure (that separates prohormones, key intermediates of intravesicular proteolysis and secreted products), and highly sensitive and specific radioimmunoassays for each hormone and for rat and human neurophysins.By employing these techniques together with automated microsequencing, three key protein intermediates of vasopressin biosynthesis and an intragranular enzyme of 22,000 daltons (proneurophysinase) have been characterized. Synthesis-secretion coupling of peptides is studied using chronically-catheterized, conscious rats. A number of techniques in molecular biology are employed to characterize and quantitate specific mRNAs, under different physiological conditions. In the field of cancer research, it has been established that vasopressin-related proteins are effective plasma markers for evaluating treatment of small cell carcinoma of the lung in two-thirds of patients suffering from this disease, and in most or all breast cancer patients. Most or all small cell tumors and breast tumors are vasopressin-producing and uniquely express provasopressin at their plasma membranes. they were found to bind antibodies to provasopressin, and this property is now being used to image tumors in patients by administering radiolabelled Fab fragments of specific antibodies and photoscanning for radiolabel. Monoclonal antibodies have also been developed to provasopressin for eventual targeted therapy. Studies have recently been extended to examine the role of NMDA receptors in small cell lung cancer and breast cancer.
Patients with Alzheimer's disease have reduced brain levels of vasopressin, oxytocin, and neurophysins. Vasopressin and its peptide fragments improve short-term memory consolidation and retrieval, while oxytocin functions as an amnesic agent. These peptides interact with cholinergic and aminergic neurons that also exhibit reduced activity in Alzheimer's disease. The hypothesis that primary pathological changes in the function of vasopressin- and oxytocin-neurons are responsible, at least in part, for the onset and severity of this disease is currently being assessed. These studies involve the use of an animal model and of peptide evaluations performed on patients who are undergoing treatment for Alzheimer's disease.
North, W.G., Fay, M.J., Du, J., Cleary, M., Gallagher, J.D., and McCann, F.V. Presence of functional NMDA receptors in a human neuroblastoma cell line. Molec. Chem. Neuropath. 30(1 2):77-94, 1997.
North, W.G. Gene Regulation of Vasopressin and Vasopressin Receptors in Cancer. Experimental Physiology, 85S: 27S-40S, 2000.
Keegan, B.P., Memoli, V.A. and North, W.G. Targeting the Neurophysin-Related Cell-Surface Antigen (NRSA) on SCLC cells using a monoclonal antibody against the glycopeptide region (MAG-1) of provasopressin. Mol. Cancer Therapeutics. 1:1153-1159, 2002.
North,W.G., Wells,W., Fay, M.J., Mathew, R.J., Donnelly, E.M., and Memoli, V.A. Immunohistochemical evaluation of vasopressin expression in breast fibrocystic disease and ductal carcinoma in situ (DCIS). Endocrin. Pathology, 14, 257-262, 2003.
Piqueux, C., Hagelstein M.T., Keegan, B., Legros, V., and North, W.G. Vasopressin and Oxytocin mitogen transduction pathway in small cell lung cancer cells. Endocr.-Relat. Cancer, 4:871-875, 2004.
North W.G., Memoli, V.A., Keegan, B.P. Immunohistochemical detection of NRSA on small cell lung cancer with a monoclonal antibody (MAG-1) that recognizes the carboxyl terminus of provasopressin. Appl Immunohistochem Mol Morphol. 13:363-366, 2005.
Keegan, B.P., Akerman, B.L., Pequeux, C. and North, W.G. Provasopressin expression by breast cancer cells: implications for growth and novel treatment strategies. Breast Cancer Res Treat. 95:265-277, 2006.
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