Cure Alzheimer's Fund Cure Alzheimer's Fund

Doo Yeon Kim, Ph.D.

Associate Professor of Neurology, Harvard Medical School; Faculty, Henry and Allison McCance Center for Brain Health, Massachusetts General Hospital

Dr. Kim has been studying pathogenic mechanisms of Alzheimer’s disease (AD) for more than 16 years. He and his team investigated physiological and pathological functions of BACE1 and presenilin/gamma secretase, two key enzymes that regulate generation of amyloid beta, a major pathogenic molecule associated with AD. Dr. Kim and his colleagues characterized four novel presenilin/gamma secretase substrate proteins and BACE1 substrate proteins that explain how BACE1 regulates neuronal activity under physiological conditions (Kim et al., Nat. Cell. Biol., 2007). Excessive amounts of BACE can disrupt the neuronal activity, making nerve cells more vulnerable to aberrant firing and perhaps seizures, which may explain the higher risk of seizures in Alzheimer’s patients. Recently, Dr. Kim’s lab, together with Dr. Rudy Tanzi’s, developed an innovative three-dimensional (3D) human stem cell culture model of AD (Choi et al., Nat., 2014). By cultivating genetically modified human neural stem cells in a 3D gel system, they were able to recapitulate key events of AD pathology, including amyloid beta plaques and neurofibrillary tangles (NFTs) for the first time. This unique human neural cell culture model can be used for large-scale, high-throughput screening for novel therapeutic targets, which is not feasible in the current AD mouse models. Kim’s “Alzheimer’s in a Dish” model has been listed as one of “10 Breakthrough Technologies of 2015” by “MIT Technology Review,” and it also won the 2015 Smithsonian American Ingenuity Award (Drs. Kim and Tanzi).

Related Research:

Funded Research

These projects were made possible from Cure Alzheimer's Fund support.

Project Description Researchers Funding
Alzheimer’s Disease Drug Discovery and Development Consortium: High-Throughput Drug Screening for Alzheimer’s Disease Using Three-Dimensional Human Neural Culture Systems 2021, 2022

$461,180
High-Throughput Drug Screening for Alzheimer’s Disease Using Three-Dimensional Human Neural Culture Systems 2020

$230,000
Exploring Sex Differences in AD Pathogenesis Using 3-D Human Non-Cell-Autonomous Models 2017

$200,000
3-D Neural Core/High-Throughput Drug Screening for Alzheimer’s Disease Using 3-D Human Neural Culture Systems 2015 to 2019

$1,682,500
Generation of Neural Progenitor Cells Overexpressing Alzheimer’s Disease Genes with Familial Mutations and Analysis of Pathological Changes of Alzheimer’s Cells in Vivo 2014

$100,000
Stem Cell Consortium 2013

$600,000
Alzheimer Disease Models Based on Human Neural Progenitor Cells 2011

$100,000

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Joseph Park, Isaac Wetzel, Ian Marriott, Didier Dréau, Carla D’Avanzo, Doo Yeon Kim, Rudolph E. Tanzi & Hansang Cho A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer’s disease, Nature Neuroscience , June 27, 2018, Read More

Steven L. Wagner, Kevin D. Rynearson, Steven K. Duddy, Can Zhang, Phuong D. Nguyen, Ann Becker, Uyen Vo, Deborah Masliah, Louise Monte, Justin B. Klee, Corinne M. Echmalian, Weiming Xia, Luisa Quinti, Graham Johnson, Jiunn H. Lin, Doo Y. Kim, William C. Mobley, Robert A. Rissman, Rudolph E. Tanzi Pharmacological and Toxicological Properties of the Potent Oral gamma-Secretase Modulator BPN-15606, Journal Of Pharmacology And Experimental Therapeutics, 362(1), Jul 2017, 31-44, Read More

Carla D'Avanzo, Jenna Aronson, Young Hye Kim, Se Hoon Choi, Rudolph E. Tanzi and Doo Yeon Kim Alzheimer’s in 3D culture: Challenges and perspectives, BioEssays, 37(10), October 2015, 1139–1148, Read More

Young Hye Kim, Se Hoon Choi, Carla D'Avanzo, Matthias Hebisch, Christopher Sliwinski, Enjana Bylykbashi, Kevin J Washicosky, Justin B Klee, Oliver Brüstle, Rudolph E Tanzi & Doo Yeon Kim A 3D human neural cell culture system for modeling Alzheimer’s disease, Nature Protocols, 10(7), June 2015, 985–1006, Read More

Carla D’Avanzo, Christopher Sliwinski, Steven L. Wagner, Rudolph E. Tanzi, Doo Yeon Kim, and Dora M. Kovacs γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation, The FASEB Journal, 29(8), 22 April 2015, 3335-3341, Read More

Jaehong Suh, Se Hoon Choi, Donna M. Romano, Moira A. Gannon, Andrea N. Lesinski, Doo Yeon Kim, Rudolph E. Tanzi ADAM10 Missense Mutations Potentiate β-Amyloid Accumulation by Impairing Prodomain Chaperone Function, Neuron, 80(2), Oct 16, 2013, 385–401, Read More

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