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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:

Funded Research

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

Project Description Researchers Funding
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.

Rudy Tanzi, Se Hoon Choi Exercise and Improved Cognition, Science , September 6, 2018, 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

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

Veeraraghavalu K, Choi SH, Zhang X, Sisodia SS Presenilin 1 Mutants Impair the Self-Renewal and Differentiation of Adult Murine Subventricular Zone-Neuronal Progenitors via Cell-Autonomous Mechanisms Involving Notch Signaling, The Journal of Neuroscience, 30(20), May 19, 2010, 6903-6915, Read More

Choi SH, Li Y, Parada LF, Sisodia SS Regulation of hippocampal progenitor cell survival, proliferation and dendritic development by BDNF, Mol Neurodegener, 4, Dec 21, 2009, 52, Read More

Meier M, Kennedy-Darling J, Choi SH, Norstrom EM, Sisodia SS, Ismagilov RF Plug-Based Microfluidics with Defined Surface Chemistry to Miniaturize and Control Aggregation of Amyloidogenic Peptides, Angewandte Chemi International Edition, Volume 48 Issue 8, February 9, 2009, 1487–1489, Read More

Choi SH, Veeraraghavalu K, Lazarov O, Marler S, Ransohoff RM, Ramirez JM, Sisodia SS Non-Cell-Autonomous Effects of Presenilin 1 Variants on Enrichment-Mediated Hippocampal Progenitor Cell Proliferation and Differentiation, Neuron, Volume 59, Issue 4, August 28, 2008, 568-580, Read More

Choi SH, Leight SN, Lee VM-Y, Li T, Wong PC, Johson JA, Saraiva MJ, Sisodia SS Accelerated Aβ Deposition in APPswe/PS1∆E9 Mice with Hemizygous Deletions of TTR (Transthyretin), J Neurosci, (26), 6/27/2007, 7006-7010, Read More

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