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MAC ADRC Join the Team |
ADRC Investigators UCSF Alzheimer's Disease Research Center (ADRC) Director: Bruce L. Miller, MD
Lennart Mucke, MD Patrick J. Fox, PhD, MSW Stephen De Armond, MD, PhD Although he brought research of astrocytes and glial neoplasms from Stanford, Dr. Stanley Prusiner invited him to add a neuropathology and immunohistochemistry component to his studies of prion diseases, which has led to a close and productive collaboration for over 20 years. The DeArmond Neuropathology Research Laboratory has focused on the cell biological and molecular mechanisms of neurodegeneration in prion diseases. His accomplishments include showing that amyloid plaques in Creutzfeldt-Jakob disease are composed of PrPSc and that accumulation of non-amyloid PrPSc in the brain is the cause of early synaptic dysfunction and degeneration and the cause of late occurring nerve cell death. Subcellular fractionation studies in his lab have shown that 10 to 50 times more PrPSc accumulates in plasma membranes of prion-infected cell lines than the normal cellular isoform, PrPC. Accumulation of PrPSc was found to change the properties of the plasma membrane and alter receptor-mediated transmembrane signaling. More recently, he has been testing whether PrP Sc accumulation alters expression of genes known to play critical roles in presynaptic and postsynaptic growth and maturation during CNS development. He found a direct correlation between synaptic PrPSc accumulation and activation of Notch-1 releasing the Notch-1 intracellular domain (NICD). NICD is a transcription factor that ultimately decreases expression of genes that maintain dendritic and axonal lengths. This finding argues that synapse degeneration in prion diseases is a programmed event (synoptosis) similar to programmed nerve cell death (apoptosis). A clinical implication of this finding is the potential that prevention of Notch-1 activation by pharmaceutical agents might prevent progressive cognitive decline in prion diseases and possibly even in other dementing disorders. Dr. DeArmond's clinical responsibilities include directing the muscle and nerve diagnostic service, participating in the brain tumor diagnostic service, and covering the autopsy brain cutting service at the UCSF affiliated hospitals. Dr. DeArmond directs several Neuropathology Cores that are integral components of human and animal prion disease program projects (PI, Dr. Stanley Prusiner) and the Neuropathology Core that is a component of the Alzheimer's Disease Research Center (PI, Dr. Bruce Miller) recently awarded to UCSF. These cores provide numerous cases of prion diseases in animals, including multiple transgenic mice; large numbers of Creutzfeldt-Jakob disease patients, some who have been given investigational drugs; and a variety of frontotemporal dementia cases. Most of these cases undergo a comprehensive quantitative clinical-neurohistological analysis or are part of other funded research questions. Michael W. Weiner, MD Dr. Weiner was one of the first investigators to obtain NMR spectra on an intact animal and began human studies with NMR and MRI in the early 1980s. He has been studying Alzheimer's disease and other neurodegenerative diseases since 1988. His research group has over 70 individuals who are developing and applying new MRI and MR spectroscopy techniques to human brain research. He was the winner of the Young Investigator Award of the American College of Cardiology, and currently has over 320 publications and over $10 million/yr of research grant support. He is the Principle Investigator of the Alzheimer's Disease Neuroimaging Initiative which is a $60 million 5-yr, multicenter study of 800 subjects who are elderly controls, mild cognitive impairment and Alzheimer's disease. Stanley B. Prusiner, MD Stanley B. Prusiner, MD is Director of the Institute for Neurodegenerative Diseases and Professor of Neurology and Biochemistry at the University of California, San Francisco where he has worked since 1972. He received his undergraduate and medical training at the University of Pennsylvania and his postgraduate clinical training at UCSF. From 1969-1972, he served in the US Public Health Service at the National Institutes of Health. Editor of 12 books and author of over 330 research articles, Prusiner’s contributions to scientific research have been internationally recognized. Prusiner is a member of the National Academy of Sciences, the Institute of Medicine, the American Academy of Arts and Sciences, the American Philosophical Society, and is a foreign member of the Royal Society, London. He is the recipient of numerous prizes, including the Potamkin Prize for Alzheimer’s Disease Research from the American Academy of Neurology (1991); the Richard Lounsberry Award for Extraordinary Scientific Research in Biology and Medicine from the National Academy of Sciences (1993); the Gairdner Foundation International Award (1993); the Albert Lasker Award for Basic Medical Research (1994); the Paul Ehrlich Prize from the Federal Republic of Germany (1995); the Wolf Prize in Medicine from the State of Israel (1996); the Keio International Award for Medical Science (1996); the Louisa Gross Horwitz Prize from Columbia University (1997); and the Nobel Prize in Physiology or Medicine (1997). In 2001, Prusiner founded InPro Biotechnology Inc., which is devoted to commercializing some of the discoveries that he and his colleagues have made at the University of California. Prusiner holds more than 35 issued or allowed United States patents all of which are assigned to the University of California and many of which are licensed to InPro Biotechnology. |