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).

To learn more, visit Dr. Kim’s profile page at Massachusetts General Hospital.

Related Research:

Exploring Novel Drug Candidates for Alzheimer’s Disease Through Integrative Pathway Analysis and Validation in 3D Cellular Models Doo Yeon Kim Luisa Quinti 2024-02-01 Alzheimer’s Disease Drug Discovery and Development Consortium: High-Throughput Drug Screening for Alzheimer’s Disease Using Three-Dimensional Human Neural Culture Systems Doo Yeon Kim Luisa Quinti 2022-02-14 High-Throughput Drug Screening for Alzheimer’s Disease Using Three-Dimensional Human Neural Culture Systems Doo Yeon Kim Luisa Quinti 2020-12-18 Exploring Sex Differences in AD Pathogenesis Using 3-D Human Non-Cell-Autonomous Models Doo Yeon Kim Daniel Irimia 2018-08-27 3-D Neural Core/High-Throughput Drug Screening for Alzheimer’s Disease Using 3-D Human Neural Culture Systems Doo Yeon Kim 2015-09-29 Generation of Neural Progenitor Cells Overexpressing Alzheimer’s Disease Genes with Familial Mutations and Analysis of Pathological Changes of Alzheimer’s Cells in Vivo Doo Yeon Kim 2015-04-21 Stem Cell Consortium Doo Yeon Kim Kevin Eggan Marc Tessier-Lavigne Sam Gandy Scott Noggle Tamir Ben-Hur 2013-03-19 Alzheimer Disease Models Based on Human Neural Progenitor Cells Doo Yeon Kim 2011-11-09

Funded Research

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

Project Description Researchers Funding
Exploring Novel Drug Candidates for Alzheimer’s Disease Through Integrative Pathway Analysis and Validation in 3D Cellular Models 2024

$210,250
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.

Naderi Yeganeh, P., Kwak, S. S., Jorfi, M., Koler, K., Kalatturu, T., von Maydell, D., Liu, Z., Guo, K., Choi, Y., Park, J., Abarca, N., Bakiasi, G., Cetinbas, M., Sadreyev, R., Griciuc, A., Quinti, L., Choi, S. H., Xia, W., Tanzi, R. E., Hide, W., Kim, D. Y. Integrative pathway analysis across humans and 3D cellular models identifies the p38 MAPK-MK2 axis as a therapeutic target for Alzheimer’s disease, Neuron, November 27, 2024, Read More

Uzoechi, S. C., Collins, B. E., Badeaux, C. J., Li, Y., Kwak, S. S., Kim, D. Y., Laskowitz, D. T., Lee, J. M., & Yun, Y. Effects of Amyloid Beta (Aβ) Oligomers on Blood-Brain Barrier Using a 3D Microfluidic Vasculature-on-a-Chip Model, Applied Sciences, May 1, 2024, Read More

Kovacs, D. M., Gersbacher, M. T., & Kim, D. Y. Alzheimer’s secretases regulate voltage-gated sodium channels, Neuroscience Letters, December 10, 2010, Read More

Sachse, C. C., Kim, Y. H., Agsten, M., Huth, T., Alzheimer, C., Kovacs, D. M., & Kim, D. Y. BACE1 and presenilin/gamma-secretase regulate proteolytic processing of KCNE1 and 2, auxilary subunits of voltage-gated potassium channels, The FASEB Journal, March 15, 2013, Read More

Chun, H., Im, H., Kang, Y. J., Kim, Y., Shin, J. H., Won, W., Lim, J., Ju, Y., Park, Y. M., Kim, S., Lee, S. E., Lee, J., Woo, J., Hwang, Y., Cho, H., Jo, S., Park, J. H., Kim, D., Kim, D. Y., Seo, J. S., Gwag, B. J., Kim, Y. S., Park K. D., Kaang, B. K., Cho, H., Ryu, H., & Lee, C. J. Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H 2 O 2- production, Nature Neuroscience, November 16, 2020, Read More

Jorfi, M., D'Avanzo, C., Kim, D. Y., & Irimia, D. Three-Dimensional Models of the Human Brain Development and Disease, Advanced Healthcare Materials, August 28, 2017, Read More

Kim, E., Kim, H., Jedrychowski, M. P., Bakiasi, G., Park, J., Kruskop, J., Choi, Y., Kwak, S. S., Quinti, L., Kim, D. Y., Wrann, C. D., Spiegelman, B. M., Tanzi, R. E., & Choi, S. H. Irisin reduces amyloid-β by inducing the release of neprilysin from astrocytes following downregulation of ERK-STAT3 signaling, Neuron, September 8, 2023, Read More

Jorfi, M., Park, J., Hall, C. K., Lin, C. J., Chen, M., von Maydell, D., Kruskop, J. M., Kang, B., Choi, Y., Prokopenko, D., Irimia, D., Kim, D. Y., & Tanzi, R. E. Infiltrating CD8+ T cells exacerbate Alzheimer’s disease pathology in a 3D human neuroimmune axis model, Nature Neuroscience, August 24, 2023, Read More

Hebisch, M., Klostermeier, S., Wolf, K., Boccaccini, A. R., Wolf, S. E., Tanzi, R. E., & Kim, D. Y. The Impact of the Cellular Environment and Aging on Modeling Alzheimer’s Disease in 3D Cell Culture Models, Advanced Science, January 15, 2023, Read More

Ning, S., Jorfi, M., Patel, S. R., Kim, D. Y., & Tanzi, R. E. Neurotechnological Approaches to the Diagnosis and Treatment of Alzheimer’s Disease, Frontiers in Neuroscience, March 24, 2022, Read More

Kim, J. J., Jorfi, M., Tanzi, R. E., Kim, D. Y., Doyle, P. S., & Irimia, D. Patterning of interconnected human brain spheroids, Lab on a Chip, September 14, 2021, Read More

Kwak, S. S., Washicosky, K. J., Brand, E., von Maydell, D., Aronson, J., Kim, S., Capen, D. E., Cetinbas, M., Sadreyev, R., Ning, S., Bylykbashi, E., Xia, W., Wagner, S. L., Choi, S. H., Tanzi, R. E., & Kim, D. Y. Amyloid-β42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer’s disease, Nature Communications, March 13, 2020, Read More

Shin, Y., Choi, S. H., Kim, E., Bylykbashi, E., Kim, J. A., Chung, S., Kim, D. Y., Kamm, R. D., & Tanzi, R. E. Blood Brain Barrier Dysfunction in a 3D in vitro model of Alzheimer’s Disease, Advanced Science, August 12, 2019, Read More

Norambuena, A., Wallrabe, H., Cao, R., Wang, D. B., Silva, A., Svindrych, Z., Periasamy, A., Hu, S., Tanzi, R. E., Kim, D. Y., & Bloom, G. S. A novel lysosome-to-micochondria signaling pathway disrupted by amyloid-beta oligomes, The EMBO Journal, October 22, 2018, Read More

Choi, S. H., Bylykbashi, E., Chatila, Z. K., Lee, S. W., Pulli, B., Clemenson, G. D., Kim, E., Rompala, A., Oram, M. K., Asselin, C., Aronson, J., Zhang, C., Miller, S. J., Lesinski, A., Chen, J. W., Kim, D. Y., van Praag, H., Spiegelman, B. M., Gage, F. H., & Tanzi, R. E. Combined Adult Neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model, Science, September 7, 2018, Read More

Park, J., Wetzel, I., Marriott, I., Dréau, D., D'Avanzo, C., Kim, D. Y., Tanzi, R. E., & Cho, H. A 3D Human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer’s disease, Nature Neuroscience, June 27, 2018, Read More

Jorfi, M., D'Avanzo, C., Tanzi, R. E., Kim, D. Y., & Irimia, D. Human Neurospheroid Arrays for in vitro studies of Alzheimer’s disease, Scientific Reports, February 5, 2018, Read More

Wagner, S. L., Rynearson, K. D., Duddy, S. K., Zhang, C., Nguyen, P. D., Becker, A., Vo, U., Masliah, D., Monte, L., Klee, J. B., Echmalian, C. M., Xia, W., Quinti, L., Johnson, G., Lin, J. H., Kim, D. Y., Mobley, W. C., Rissman, R. A., & Tanzi, R. E. Pharmacological and Toxicological Properties of the Potent Oral gamma-secretase modulator BPN-15606, Journal of Pharmacology and Experimental Therapeutics, July 1, 2017, Read More

Choi, S. H., Kim, Y. H., Quinti, L., Tanzi, R. E., & Kim, D. Y. 3D Culture Models of Alzheimer’s disease: a road map to a “cure-in-a-dish”, Molecular Neurodegeneration, December 9, 2016, Read More

D'Avanzo, C., Aronson, J., Kim, Y. H., Choi, S. H., Tanzi, R. E., & Kim, D. Y. Alzheimer’s in 3D culture: Challenges and Perspectives, BioEssays, October 1, 2015, Read More

Hyman, B. T., Growdon, J. H., Albers, M. W., Buckner, R. L., Chhatwal, J., Gomez-Isla, M. T., Haass, C., Hudry, E., Jack, C. R., Jr, Johnson, K. A., Khachaturian, Z. S., Kim, D. Y., Martin, J. B., Nitsch, R. M., Rosen, B. R., Selkoe, D. J., Sperling, R. A., St George-Hyslop, P., Tanzi, R. E., Yap, L., Young, A. B., Phelps, C. H., & McCaffrey, P.M. Massachusetts Alzheimer’s Disease Research Center: Progress and Challenges, Alzheimer's & Dementia, October 1, 2015, Read More

Kim, Y. H., Choi, S. H., D'Avanzo, C., Hebisch, M., Sliwinski, C., Bylykbashi, E., Washicosky, K. J., Klee, J. B., Brüstle, O., Tanzi, R. E., & Kim, D. Y. A 3D human neural cell culture system for modeling Alzheimer’s disease, Nature Protocols, July 1, 2015, Read More

D'Avanzo, C., Sliwinski, C., Wagner, S. L., Tanzi, R. E., Kim, D. Y., & Kovacs, D. M. Gamma-Secretase modulators reduce endogenous amyloid beta (42) levels in human neural progenitor cells without altering neuronal differentiation, The FASEB Journal, April 22, 2015, Read More

Choi, S. H., Kim, Y. H., Hebisch, M., Sliwinski, C., Lee, S., D'Avanzo, C., Chen, H., Hooli, B., Asselin, C., Muffat, J., Klee, J. B., Zhang, C., Wainger, B. J., Peitz, M., Kovacs, D. M., Woolf, C. J., Wagner, S. L., Tanzi, R. E., & Kim, D. Y. A three-dimensional human neural cell culture model of Alzheimer’s disease, Nature, October 12, 2014, Read More

Suh, J., Choi, S. H., Romano, D. M., Gannon, M. A., Lesinski, A. N., Kim, D. Y., & Tanzi, R. E. ADAM10 Missense Mutations Potentiate beta-amyloid accumulation by impairing pro-domain chaperone function, Neuron, September 19, 2013, Read More

Zhang, C., Browne, A., Kim, D. Y., & Tanzi, R. E. Familial Alzhiemer’s Disease mutations in presenilin 1 do not alter levels of the secreted amyloid-protein precursor generated by beta-secretase cleavage, Current Alzheimer Research, February 1, 2010, Read More

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