Se Hoon Choi, Ph.D.

In the pursuit to understand Alzheimer’s disease (AD), my overall research objectives are to explore the roles of adult-generated neurons (adult hippocampal neurogenesis, AHN) in AD, to develop three-dimensional (3D) human neural cell culture models with application to AD in order to reveal pathological mechanisms of AD and find novel therapeutic targets, and to uncover the molecular mechanisms linking exercise hormone irisin to neuroprotection in AD. My ultimate goal is to identify novel, alternative druggable targets to treat cognitive decline in aging and neurodegenerative diseases. AHN is impaired in AD patients. We 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. Inducing both neurogenesis and BDNF may be useful as an AD therapeutic. We developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. Our 3D culture system successfully recapitulates key events of AD pathology including amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs) for the first time (Choi et al., Nature 2014). We also found that irisin has the ability to reduce amyloid-β pathology by increasing the release of neprilysin from astrocytes following downregulation of ERK-STAT3 signaling(Kim et al. 2023 Neuron). All these contributions represent small steps toward understanding and treating AD. I have developed extensive research experience and expertise in AD, AHN, and the 3D cell culture system, along with a broad background in neurobiology. My work has been accomplished through independent productivity as well as extensive collaborations with other leading experts with whom I have shared my unique expertise.