Ralph A. Nixon, MD, PhD

Ralph A. Nixon, MD, PhD

Director of Research and The Center for Dementia Research
Nathan S. Kline Institute for Psychiatric Research Nixon Lab Page
Professor of Psychiatry and Cell Biology
NYU Langone Medical Center Nixon NYU Page

P: (845)398-5423
F: (845)398-5422


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A.B. Brandeis University, Waltham, MA
Ph.D. Harvard University, Cambridge, MA (Cell and Developmental Biology)
M.D. University of Vermont, College of Medicine, Burlington, VT
Postdoctoral Training
Medical Intern, Salem Hospital, Salem, MA
Resident in Psychiatry, Massachusetts General Hospital, Boston, MA
Resident in Psychiatry, McLean Hospital, Belmont, MA

Awards and Honors

1976 Herbert Martin, Sr., Neurology Prize
1976 University of Vermont General Research Award
1979-1980 Ethel DuPont Warren Fellowship Award
1980-1982 Medical Foundation Research Fellowship Award
1981-1983 Alfred P. Sloan Foundation Fellowship Award
1983-1985 Scottish Rite Schizophrenia Research Program Fellowship Award
1990-present MERIT Award, National Institutes of Health
1992-1999 LEAD Award (Leadership and Excellence in Alzheimer Research), National Institute on Aging
1994-1995 Chairman, Neuroscience, Behavior and Sociology of Aging Review Committee, National Institute on Aging
1999-present Academic Career Leadership Award, National Institute on Aging
1999 Temple Foundation Discovery Award – Alzheimer’s Association
1999 Research Award for 1999, New York State Office of Mental Health
2003 Zenith Award, Alzheimer's Association
2004 Election to American College of Neuropsychopharmacology (ACNP)
2008 Vice Chairman, Medical and Scientific Advisory Committee, National Alzheimer’s Association
2011 Chairman, Medical and Scientific Advisory Council, National Alzheimer’s Association
2011 Member, Board of Directors, National Alzheimer’s Association
2011 Fellow, American College of Neuropsychopharmacology (ACNP)

Research Interests

The Fate of Pathogenic Proteins in Neurodegenerative Diseases

In major neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, the abnormal accumulation of one or more polypeptides within or around neurons is central to pathogenesis. Our research focuses on two aspects of neurobiology that govern the fate of normal and pathogenic proteins: the regulation of proteolytic processing and the control of protein export into axons and synapses. We have identified dysfunction of the endosomal-lysosomal system, involving altered endocytosis and mistrafficking of proteases to endosomes, as the earliest known pathological response of neurons in Alzheimer’s disease. Our cell modeling studies show early endosomes to be major generators of the toxic ß-amyloid peptide and implicate dysfunction of endosomes in the mechanism of ß-amyloid accumulation in "sporadic" Alzheimer’s, the most common form of the disease. Genetic manipulations of proteolytic systems in mice are being used, together with cell culture models, to determine the consequences of endosomal-lysosomal and calpain system dysfunction on processing of Alzheimer-related proteins, receptor-mediated signal transduction, and neuronal cell death pathways.

To maintain neural circuitry, neurons transport a large proportion of their newly synthesized proteins into axons. The perikaryal accumulation of specific cytoskeletal proteins - a pathological hallmark of Alzheimer’s, ALS, and other neurologic diseases - is believed to arise in part from impaired axonal transport. A second interest of our research is to identify the molecular determinants of cytoskeletal protein transport and assembly in neurons. For example, we are defining the minimum structural requirements for neurofilament translocation by studying axonal transport and axon ultrastructure in mice after targeted deletion or mutagenesis of each of the three neurofilament subunit genes. Neurofilament transport is also regulated by sequential protein phosphorylation, triggered in part by signals from oligodendroglial cells. We have been determining the signaling pathways, phosphorylation sites, and functional implications of these post-translational modifications. Disease relevance is also being explored in several behavioral and psychiatric settings.