David G. Cook, Ph.D.

Biosketch Information
Email: dgcook@u.washington.edu The overall objective of the merit review award is to investigate the maturation kinetics, trafficking, and long-term accumulation of intracellular Amyloid-beta in human NT2N neurons. We are also involved in a project with Dr. Raskind’s Alzheimer’s Disease Research Center. The overall objective of this grant is to gain insight into the mechanisms by which the presenilins (PS1 and PS2) influence the processing of the amyloid precursor protein (APP) and the generation of Amyloid-beta. Familial mutations in PS1 and PS2 cause increased Amyloid-beta. This project is aimed at determining the subcellular sites where APP and presenilins functionally interact to alter APP/Amyloid-beta metabolism.

Dr. Cook is Research Assistant Professor in Medicine, Division of Gerontology and Geriatric Medicine, and Adjunct Research Assistant Professor in Pharmacology. He works currently as GRECC Research Biologist, Veterans Affairs Puget Sound Health Care System. He is PI of a Veterans Affairs Merit Review Award entitled “Role of APP and Presenilins in Neuronal Intracellular A-beta Metabolism.”

Selected Relevant Publications
Chyung ASC, Greenberg BD, Cook DG, Doms RW, Lee VM-Y. Unique neuronal pathways for the metabolism of beta-amyloid and beta-amyloid precursor proteins. J Cell Biol 138:671-680, 1997.

Cook DG, Forman M, Sung JC, Lee VM-Y, Doms RW. Amyloid-beta peptide (Aß) 1-42 is generated in the endoplasmic reticulum of NT2-N cells. Nat Med 3:1021-1023, 1997.

Forman M, Cook DG, Leight S, Doms RW, Lee VM-Y. Differential effects of the Swedish mutant amyloid precursor protein on ß-amyloid accumulation in neurons and non-neuronal cells. J Biol Chem 272:32247-32253, 1997.

Cook DG, Forman MS, Chyung ASC, Doms RW, Lee VM-Y. Biosynthesis of APP and Aß: multiple pathways for the generation of intracellular Aß. In: Molecular Biology of Alzheimer's Disease. C Haass, ed. Harwood Academic Publishers, 1998. pp 111-132.

Linford NJ, Yang Y, Cook DG, Dorsa DM. Neuronal apoptosis resulting from high doses of the isoflavone genistein: role for calcium and P42/44 mitogen-activated protein kinase. J Pharmacol Exper Ther 299:67-75, 2001.

Shie F-S, Lin L-W, Cook DG, Leverenz JB, Leboeuf RC. Diet-induced hypercholesterolemia enhances brain Aß accumulation in transgenic mice. Neuroreport, in press.