Ralph A. Nixon, MD, PhD
Dr. Nixon is currently Professor of the Departments of Psychiatry and Cell Biology and Director of the Silberstein Institute. He has applied training in cell biology and clinical psychiatry toward the understanding of mechanisms underlying neurodegenerative diseases and the development of treatments for Alzheimer’s Disease (AD) and related disorders. An overarching concept of research in his lab is special vulnerabilities of neurons to degenerative diseases stemming from their unusual polar shapes that allow them to communicate with each other over long distances. His lab focuses on two of these vulnerabilities - (1) the bidirectional sorting and delivery of organelles and proteins back and forth from synapses, which is important for signaling and synaptic activity, and (2) the regulation of protein turnover. Because neurons cannot divide yet must remain plastic throughout life, neurons rely heavily on mechanisms to recycle proteins and organelles that become obsolete or damaged, a need that increases with age. Underscoring the importance of these processes in AD, they have found that genes causing AD or increasing its risk are critical to regulating intracellular trafficking and waste recycling in neurons and that disease-causing mutations disrupt this regulation leading to pathology. These directions of research are being explored usinga broad range of molecular, cellular and structural methods in cell and animal models of disease. These studies have led toward innovative approaches to the therapy of AD and related conditions, which are also currently being validated.
- Yang DS, Stavrides P, Mohan P, Kaushik S, Kumar A, Ohno M, Schmidt SD, Wesson D, Bandyopadhyay U, Jiang Y, Pawlik M, Peterhoff PM, Yang AJ, Wilson DA, St George-Hyslop P, Westaway D, Mathews PM, Levy E, Cuervo AM, Nixon RA. (2011) Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits. Brain. 134(1): 258-277.
Lee SY, Sato Y, Nixon RA. (2011) Lysosomal proteolysis inhibition selectively disrupts axonal transport of degradative organelles and causes an Alzheimer’s-like axonal dystrophy. Journal of Neuroscience. 31(21): 7817-7830.
Lee JH, Yu WH, Kumar A, Lee S, Mohan PS, Peterhoff CM, Martinez-Vicente M, Massey AC, Sovak G, Uchiyama Y, Westaway D, Cuervo AM, Nixon RA. (2010) Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell. 141: 1146-1158.
- Ginsberg SD, Alldred M, Counts SE, Cataldo AM, Neve RL, Jiang Y, Wuu J, Chao MV, Mufson EJ, Nixon RA, Che S. (2010) Microarray analysis of hippocampal CA1 neurons implicates early endosomal dysfunction during Alzheimer’s disease progression. Biological Psychiatry. 68:885-893.
- Jiang Y, Mullaney KA, Peterhoff C, Che S, Schmidt SD, Boyer-Boiteau A, Ginsberg SD, Cataldo AM, Mathews PM, Nixon RA. (2010) Alzheimer’s-related endosome dysfunction in Down syndrome is Abeta-independent but requires APP and is reversed by BACE-1 inhibition. Proceedings of the National Academy of Sciences. 107:1630-1635.
- Dyakin VV, Chen Y, Branch CA, Veeranna, Yuan A, Rao M, Kumar A, Peterhoff C, Nixon RA. (2010) The contributions of myelin and axonal caliber to transverse relaxation time in shiverer and neurofilament-deficient mouse models. NeuroImage. 51:1098-1105.
- Veeranna, Yang DS, Lee JH, Vinod KY, Stavrides P, Amin ND, Pant HC, Nixon RA. (2009) Declining phosphatases underlie aging-related hyperphosphorylation of neurofilaments. Neurobiology of Aging. 32(11): 2016-2029.
- Ihara Y, Morishima-Kawashima M, Nixon RA. The ubiquitin-proteasome system and the autophagic-lysosomal system in Alzheimer disease. In: The Biology of Alzheimer Disease. Selkoe D, Holtzman D, Mandelkow E (Eds.). Woodbury NY, USA: Cold Spring Harbor Laboratory Press., in press. [Chapter 19] ISBN:978-1-936113-44-6