Doo Yeon Kim, Ph.D.

Assistant Professor of Neurology, Harvard Medical School

Assistant in Neurology, Genetics and Aging Research Unit, Massachusetts General Institute for Neurodegenerative Diseases, Department of Neurology, Massachusetts General Hospital

Dr. Kim received his Ph.D. at Korea Advanced Institute of Science and Technology (KAIST), South Korea. He started his postgraduate work at the Brain Disease Research Center, Ajou University Medical School, South Korea, and completed his post doctorate at Dr. Dora M. Kovacs’ laboratory at Massachusetts General Hospital, where he was appointed assistant professor in 2009. He was awarded a fellowship from the John Douglas French Alzheimer's Foundation in 2004. Dr. Kim has been investigating physiological and pathological functions of Alzheimer’s disease-related secretases, BACE1 and presenilin/g-secretase, since 2001. BACE1 and g-secretase play a major role in Alzheimer’s disease pathogenesis by regulating Ab-peptide generation.

Funded Research

Project Description Researchers Funding
3-D Neural Core/High-Throughput Drug Screening for Alzheimer’s Disease Using 3-D Human Neural Culture Systems

The “beta-amyloid cascade hypothesis” of Alzheimer's disease (AD) has provided a major framework for AD drug discovery and has led to many current clinical trials. However, to date, no single in vitro or in vivo AD model has been able to recapitulate the presumed patient pathophysiology: beta-amyloid deposition directly leads to tangles and neurodegeneration. Recently, we created a novel three­ dimensional (3-D) human neural cell culture model of AD using genetically engineered human neural stem cells.

2015 to 2016

Generation of Neural Progenitor Cells Overexpressing Alzheimer’s Disease Genes with Familial Mutations and Analysis of Pathological Changes of Alzheimer’s Cells in Vivo

We seek to evaluate the impact of candidate AD drugs on Abeta and tau pathology in human cellular AD models. In collaboration with Dr. Tanzi’s laboratory (Massachusetts General Hospital), we will test the impact of select candidate AD drugs on both Abeta and tau pathology in the 30 human neural cell culture models developed in Aim 4. In the first year, we found that SGSM41i, a candidate AD drug designed to specifically decrease the toxic Abeta42 generation, decreases not only the Abeta plaques but also the tau pathology in the 30 human cellular AD models.

Stem Cell Consortium

Stem cells are the least mature cells in the body. Because these cells are so immature, they can be treated with a defined cocktail of factors and, depending on which factors are used and in what sequence, those factors can cause maturation of cells along discrete cell types. With a new tool called induced pluripotent stem cells, it now is possible to take skin cells from adults and return them to this immature state. By redirecting skin cells from Alzheimer’s patients and turning them into nerve cells, we are able to study adult Alzheimer’s neurons (nerve cells) in the lab.

Alzheimer Disease Models Based on Human Neural Progenitor Cells

The goal of this project is to develop genetically modified human neural progenitor cells that can replicate Alzheimer’s disease pathology in in vitro and in vivo conditions in order to develop and test Alzheimer disease drugs in human brain cells.


Selected Publications

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