Se Hoon Choi, Ph.D.

Assistant Professor of Neurology, Harvard Medical School; Faculty, Genetics and Aging Research Unit, McCance Center for Brain Health, Massachusetts General Hospital; Affiliate, Harvard Stem Cell Institute (HSCI)

 


Dr. Choi is an Assistant Professor of Neurology at Massachusetts General Hospital (MGH) and Harvard Medical School (HMS). He has been exploring pathogenic mechanisms of Alzheimer’s disease (AD) and the role of adult-generated neurons, adult hippocampal neurogenesis (AHN), in the disease.

Previously, Dr. Choi got his PhD in Neurobiology from University of Chicago. Mentored by Dr. Sangram Sisodia, he found that the expression of Familial Alzheimer’s disease (FAD)-linked presenilin 1 (PSEN1) variants regulates adult hippocampal neurogenesis (Choi et al.Neuron 2008). During his postdoctoral research training in the laboratory of Dr. Rudolph Tanzi at MGH and HMS, his research found that inducing AHN alone did not improve cognition in AD mice, whereas inducing neurogenesis while simultaneously ameliorating the neuronal environment via exercise did (Choi et al.Science 2018). Using genetic or pharmacological treatments that simultaneously induced neurogenesis and increased levels of brain-derived neurotrophic factor (BDNF) mimicked the benefits of exercise on cognition.

His research also led to the development of a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. The 3D culture system successfully recapitulates key events of AD pathology including amyloid plaques and neurofibrillary tangles for the first time (Choi et al., Nature 2014). In collaboration with Dr. Roger Kamm at MIT, he also contributed to developing a 3D culture system with an intact vascular wall in a 3D microfluidic platform to study direct effects of the AD pathological microenvironment on brain endothelial cells, a major component of the blood-brain barrier (BBB) (Shin et al., Advanced Science 2019).

Dr. Choi’s current research projects include exploration AHN as a potential therapeutic target for improving cognitive function and promoting synaptic resilience in AD, studying the effects of exercise on AD pathogenesis, developing most physiological relevant 3D BBB models in collaboration with Dr. Roger Kamm (MIT), and studying effects of exercise hormone, irisin, on AD pathogenesis in collaboration with Dr. Christiane Wrann (MGH).

Related Research:

Brain Exit and Entry Consortium: Human Three-Dimensional Neurovascular Interaction and Meningeal Lymphatics Models with Application to Alzheimer’s Disease Se Hoon Choi 2024-05-02 Neuroprotective Effects of the Exercise Hormone Irisin in Alzheimer’s Disease Se Hoon Choi Christiane Wrann 2023-10-25 Brain Entry and Exit Consortium: A 3D In Vitro Neurovascular Human Brain Model With Meningeal Lymphatics for Elucidating Mechanisms Underlying Alzheimer’s Disease Se Hoon Choi 2023-05-02 Neuroprotective Effects of the Exercise Hormone Irisin in Alzheimer’s Disease Se Hoon Choi Christiane Wrann 2022-06-23 Identifying Blood-Brain Barrier (BBB) Enhancers and Role of Neutrophils in a 3-D BBB Vascularized Model of Alzheimer’s Disease Roger D. Kamm Se Hoon Choi 2022-01-11 Berg Brain Entry and Exit Consortium: Human 3D Neurovascular Interaction and Meningeal Lymphatics Models with Application to Alzheimer’s Disease Se Hoon Choi Roger D. Kamm 2019-12-17 Neuroprotective Effects of the Exercise Hormone Irisin in Alzheimer’s Disease Se Hoon Choi Christiane Wrann 2018-12-27 Evaluation of Blood-Brain Barrier (BBB) Penetration of Alzheimer’s Drug Targets, and Identification of BBB Integrity Enhancers Roger D. Kamm Se Hoon Choi 2018-08-09 Role of Blood-Brain Barrier Function in Alzheimer’s Disease Pathogenesis Investigated Using a 3-D Microfluidic Platform Se Hoon Choi Roger D. Kamm 2015-09-29 Exploring Adult Neurogenesis as a Therapeutic Target for Alzheimer’s Disease Se Hoon Choi 2011-11-09

Funded Research

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

Project Description Researchers Funding
Brain Exit and Entry Consortium: Human Three-Dimensional Neurovascular Interaction and Meningeal Lymphatics Models with Application to Alzheimer’s Disease 2024

$287,500

Neuroprotective Effects of the Exercise Hormone Irisin in Alzheimer’s Disease 2023

$345,000

Brain Entry and Exit Consortium: A 3D In Vitro Neurovascular Human Brain Model With Meningeal Lymphatics for Elucidating Mechanisms Underlying Alzheimer’s Disease 2023

$230,000

Neuroprotective Effects of the Exercise Hormone Irisin in Alzheimer’s Disease 2021, 2022

$700,000

Identifying Blood-Brain Barrier (BBB) Enhancers and Role of Neutrophils in a 3-D BBB Vascularized Model of Alzheimer’s Disease 2018

$268,750

Berg Brain Entry and Exit Consortium: Human 3D Neurovascular Interaction and Meningeal Lymphatics Models with Application to Alzheimer’s Disease 2019, 2021

$430,000

Neuroprotective Effects of the Exercise Hormone Irisin in Alzheimer’s Disease 2018, 2020

$700,000

Evaluation of Blood-Brain Barrier (BBB) Penetration of Alzheimer’s Drug Targets, and Identification of BBB Integrity Enhancers 2017

$200,000

Role of Blood-Brain Barrier Function in Alzheimer’s Disease Pathogenesis Investigated Using a 3-D Microfluidic Platform 2015, 2016

$584,900

Exploring Adult Neurogenesis as a Therapeutic Target for Alzheimer’s Disease 2011

$100,000

Selected Publications

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

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

Choi, S. H., Li, Y., Parada, L. F., & Sisodia, S. S. Regulation of hippocampal progenitor cell survival, proliferation, and dendritic development by BDNF, Molecular Neurodegeneration, December 21, 2009, Read More

Meier, M., Kennedy-Darling, J., Choi, S. H., Norstrom, E. M., Sisodia, S. S., & Ismagilov, R. F. Plug-based microfluidics with defined surface chemistry to miniaturize and control aggregation of amyloidogenic peptides, Angewandte Chemie (International ed. in English), January 30, 2009, 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

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

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

Islam, M. R., Valaris, S., Young, M. F., Haley, E. B., Luo, R., Bond, S. F., Mazuera, S., Kitchen, R. R., Caldarone, B. J., Bettio, L. E. B., Christie, B. R., Schmider, A. B., Soberman, R. J., Besnard, A., Jedrychowski, M. P., Kim, H., Tu, H., Kim, E., Choi, S. H., Tanzi, R. E., … Wrann, C. D. Exercise hormone irisin is a critical regulator of cognitive function, Nature Metabolism, August 20, 2021, Read More

Mondal, P., Bai, P., Gomm, A., Bakiasi, G., Lin, C. J., Wang, Y., Choi, S. H., Tanzi, R. E., Wang, C., & Zhang, C. Structure-Based Discovery of A Small Molecule Inhibitor of Histone Deacetylase 6 (HDAC6) that Significantly Reduces Alzheimer’s Disease Neuropathology, Advanced Science, November 21, 2023, Read More

Bai, P., Mondal, P., Bagdasarian, F. A., Rani, N., Liu, Y., Gomm, A., Tocci, D. R., Choi, S. H., Wey, H. Y., Tanzi, R. E., Zhang, C., & Wang, C. Development of a potential PET probe for HDAC6 imaging in Alzheimer’s disease, Acta Pharmaceutica Sinica B, May 20, 2022, Read More

Zhang, S., Bai, P., Lei, D., Liang, Y., Zhen, S., Bakiasi, G., Pang, H., Choi, S. H., Wang, C., Tanzi, R. E., & Zhang, C. Degradation and inhibition of epigenetic regulatory protein BRD4 exacerbate Alzheimer’s disease-related neuropathology in cell models, Journal of Biological Chemistry, March 3, 2022, Read More

Liang, Y., Raven, F., Ward, J. F., Zhen, S., Zhang, S., Sun, H., Miller, S. J., Choi, S. H., Tanzi, R. E., & Zhang, C. Upregulation of Alzheimer’s Disease Amyloid-beta Protein Precursor in Astrocytes Both in vitro and in vivo, Journal of Alzheimer's Disease, August 4, 2020, Read More

Choi, S. H., & Tanzi, R. E. Adult neurogenesis in Alzheimer’s disease, Hippocampus, February 7, 2023, Read More

Wang, Z., Ye, J., Zhang, K., Ding, L., Granzier-Nakajima, T., Ranasinghe, J. C., Xue, Y., Sharma, S., Biase, I., Terrones, M., Choi, S. H., Ran, C., Tanzi, R. E., Huang, S. X., Zhang, C., & Huang, S. Rapid Biomarker Screening of Alzheimer’s Disease by Interpretable Machine Learning and Graphene-Assisted Raman Spectroscopy, ASC Nano, March 25, 2022, 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

Raven, F., Ward, J. F., Zoltowska, K. M., Wan, Y., Bylykbashi, E., Miller, S. J., Shen, X., Choi, S. H., Rynearson, K. D., Berezovska, O., Wagner, S. L., Tanzi, R. E., & Zhang, C. Soluble Gamma-secretase Modulators Attenuate Alzheimer’s beta amyloid pathology and induce conformational changes in presenili 1, eBioMedicine, September 4, 2017, Read More

Salta, E., Lazarov, O., Fitzsimons, C. P., Tanzi, R., Lucassen, P. J., & Choi, S. H. Adult hippocampal neurogenesis in Alzheimer’s disease: A roadmap to clinical relevance, Cell Stem Cell, February 2, 2023, Read More

Griciuc, A., Patel, S., Federico, A. N., Choi, S. H., Innes, B. J., Oram, M. K., Cereghetti, G., McGinty, D., Anselmo, A., Sadreyev, R. I., Hickman, S. E., El Khoury, J., Colonna, M., & Tanzi, R. E. TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer’s Disease, Neuron, July 10, 2019, 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

Ko, E. C., Spitz, S., Pramotton, F. M., Barr, O. M., Xu, C., Pavlou, G., Zhang, S., Tsai, A., Maaser-Hecker, A., Jorfi, M., Choi, S. H., Tanzi, R. E., & Kamm, R. D. Accelerating the in vitro emulation of Alzheimer’s disease-associated phenotypes using a novel 3D blood-brain barrier neurosphere co-culture model, Frontiers in Bioengineering and Biotechnology, October 9, 2023, Read More

Liang, Y., Lee, D. Y. W., Zhen, S., Sun, H., Zhu, B., Liu, J., Lei, D., Lin, C. J., Zhang, S., Jacques, N. A., Quinti, L., Ran, C., Wang, C., Griciuc, A., Choi, S. H., Dai, R. H., Efferth, T., Tanzi, R. E., & Zhang, C. Natural medicine HLXL targets multiple pathways of amyloid-mediated neuroinflammation and immune response in treating alzheimer’s disease, Phytomedicine, May 13, 2022, 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

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

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

Kumar, D. K., Choi, S. H., Washicosky, K. J., Eimer, W. A., Tucker, S., Ghofrani, J., Lefkowitz, A., McColl, G., Goldstein, L. E., Tanzi, R. E., & Moir, R. D. Amyloid-beta peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease, Science Translational Medicine, May 25, 2016, Read More

McAlpine, C. S., Park, J., Griciuc, A., Kim, E., Choi, S. H., Iwamoto, Y., Kiss, M. G., Christie, K. A., Vinegoni, C., Poller, W. C., Mindur, J. E., Chan, C. T., He, S., Janssen, H., Wong, L. P., Downey, J., Singh, S., Anzai, A., Kahles, F., Jorfi, M., Feruglio, P.F., Sadreyev, R. I., Weissleder, R., Kleinstiver, B. P., Nahrendorf, M., Tanzi, R. E., & Swirski, F. K. Astrocytic interleukin-3 programs microglia and limits Alzheimer’s disease, Nature, July 14, 2021, Read More

Griciuc, A., Serrano-Pozo, A., Parrado, A. R., Lesinski, A. N., Asselin, C. N., Mullin, K., Hooli, B., Choi, S. H., Hyman, B. T., & Tanzi, R. E. Alzheimer’s disease risk gene CD33 inhibits microglial uptake of amyloid beta, Neuron, May 22, 2013, Read More