Dain Lee

All Publications

• Bottom-Up Engineering of a Human Neuromuscular System for Modeling Activity-Induced Remodeling, Metabolic Stress, and Endothelial-Modulated Excitability. Advanced materials (Deerfield Beach, Fla.) Ahn, J., Kim, M. S., Kim, J. H., Kang, S. H., Lee, D., Liu, H. W., Shin, S. C., Na, K., Jun, Y., Hong, O. K., Yang, J. H., Kim, J. A., Jang, H., Kim, H. N., Kamm, R. D., Kim, J. H., Son, J. W., Chung, S. 2026: e74851

  Abstract

  In vitro models of the human neuromuscular system recapitulate key features of neuromuscular connectivity and are increasingly used to study disease mechanisms. However, activity-dependent adaptation and the contribution of endothelial cells (ECs) remain incompletely represented in vitro. Here, we establish a bottom-up, microchip-based method that supports motor innervation of three-dimensional (3D) human muscle and permits local or bath application of defined chemical stimuli. The same architecture also supports endothelial ingrowth, producing myobundles with concurrent neural and endothelial integration. Repeated local L-glutamate stimulation induced structural, metabolic, and transcriptional changes associated with activity-dependent muscle adaptation, whereas high-glucose exposure produced a distinct, largely opposing response. Addition of ECs further altered calcium dynamics in motor neurons (MNs) and innervated muscle fibers. This modular method enables controlled investigation of responses to neural, metabolic, and endothelial cues in engineered human neuromuscular system.

  View details for DOI 10.1002/adma.74851

  View details for PubMedID 42695474

• Optogenetic engineering of BAX to control mitochondrial permeabilization and attenuate apoptosis in cells. Experimental & molecular medicine Lee, D., Bae, H., Oh, D., Kim, M., Kim, J. H., Ahn, J., Kang, S. H., You, S. H., Kim, D. H., Oh, H. J., Heo, W. D., Chung, S. 2025

  Abstract

  Although considerable research has focused on enhancing the apoptotic function of BAX for several decades, inhibition of its functionality remains relatively underexplored, despite intensive BAX activation occurring in various neurodegenerative diseases. Here we present a protein engineering approach to modulate BAX integration into the mitochondrial outer membrane, establishing a tunable strategy for antiapoptosis. Utilizing optogenetic methods that employ cryptochrome 2 and its binding partner cryptochrome-interacting basic helix loop helix 1, we achieved precise spatial control over BAX localization, a critical determinant of its function. Our results demonstrate that the engineered BAX variant is effectively incapacitated in its apoptotic function while also modulating endogenous BAX activity to enhance cellular resistance to apoptosis. These findings not only advance our understanding of BAX regulation but also offer promising prospects for the development of therapeutic strategies against apoptosis-related diseases.

  View details for DOI 10.1038/s12276-025-01605-y

  View details for PubMedID 41449208

  View details for PubMedCentralID 3050027

• Portable platform for measuring amyloid beta 42/40 ratio via photooxidation-induced fluorescence amplification. Lab on a chip Ko, S., Bae, H., Kim, D., Lee, Y., Choi, I., Lee, D., Choi, D. H., Kim, H. C., Sohn, S. Y., Jeong, Y., Chung, S., Jung, Y. H. 2025; 25 (16): 3993-4001

  Abstract

  Alzheimer's disease (AD) is a serious health condition that exacerbates with age. Among various AD biomarkers, the measurement of the Aβ 42/40 ratio (i.e., ratio of Aβ 42 and Aβ 40 concentrations) has garnered prominence for the early identification of AD patients and the development of disease-modifying treatments. Approaches such as positron emission tomography examinations and biomarker measurements in cerebrospinal fluid and blood plasma face constraints related to expense and procedural complexity. To address these issues, we developed and evaluated the efficacy of a portable platform for detecting amyloid beta (Aβ) 40 and 42 in plasma, utilizing photooxidation-induced fluorescence amplification (PIFA). We conducted a comparative analysis of Aβ 42/40 measurements between the PIFA and single-molecule immunoassay (SiMoA) platforms. By measuring 38 cases of subjective cognitive decline (SCD), 24 cases of amnestic mild cognitive impairment (aMCI), and 46 cases of AD dementia samples, we observed a significant difference in Aβ 42/40 ratios between the SCD and aMCI groups. The PIFA platform demonstrated an area under the curve compared to that of the SiMoA platform, which is currently the most precise method for Aβ 42/40 ratio measurement. Consequently, the PIFA platform presents a viable cost-effective tool for detecting the Aβ 42/40 ratio.

  View details for DOI 10.1039/d5lc00235d

  View details for PubMedID 40546070

• β-Ionone suppresses colorectal tumorigenesis by activating OR51E2, a potential tumor suppressor. Phytomedicine : international journal of phytotherapy and phytopharmacology Kim, J. S., Cho, S., Jeong, M. Y., Rivera-Piza, A., Kim, Y., Wu, C., Yoon, Y. E., Lee, I., Choi, J. W., Lee, H. L., Shin, S. W., Shin, J., Gil, H., Lee, M. G., Keum, N., Kim, J. A., Lee, D., Jung, Y. H., Chung, S., Shin, M. J., Hong, S., Chi, S. G., Lee, S. J. 2025; 140: 156599

  Abstract

  Olfactory receptors (ORs) are present in non-olfactory tissues and contribute to diverse biological roles beyond smell perception. Among them, OR51E2 has been associated with cancer biology, and its activator, β-ionone, a natural terpenoid, is known to have anticancer effects.This study aimed to clarify the tumor-suppressive role of OR51E2 in colorectal cancer (CRC), unravel the regulatory mechanism underlying its downregulation, and evaluate the therapeutic potential of β-ionone, an OR51E2 ligand, in CRC progression.OR51E2 expression was analyzed in human CRC tissues, matched adjacent normal tissues, and cell lines. The involvement of N6-methyladenosine (m6A) modification of OR51E2 mRNA stability was examined using METTL3/14 and YTHDF1/2/3 knockdown experiments. β-Ionone-mediated effects on intracellular calcium signaling, cell proliferation, migration, and apoptosis were evaluated in an OR51E2-dependent manner. The therapeutic efficacy of β-ionone was further evaluated in vivo using a xenograft model in nude mice.OR51E2 mRNA expression and immunoreactivity were significantly reduced in CRC cells and tissues due to decreased mRNA stability. Knockdown of METTL3/14 or YTHDF1/2/3 increased OR51E2 mRNA and protein expression and inhibited CRC cell proliferation. Treatment with STM2457, an METTL3 inhibitor, restored OR51E2 expression and suppressed CRC cell proliferation. β-Ionone, a ligand of OR51E2, increased intracellular calcium levels, decreased MEK/ERK phosphorylation, and inhibited CRC cell proliferation while inducing apoptosis. These effects were abolished in OR51E2 knockdown cells. In a xenograft model, β-ionone administration (5 and 10 mg/kg body weight) significantly reduced tumor growth.This study identifies m6A modification as a critical mechanism underlying the downregulation of OR51E2 in CRC. Activation of OR51E2 by β-ionone suppresses CRC cell proliferation and induces apoptosis by elevating intracellular calcium levels, which inhibits the MEK-ERK pathway. These findings highlight OR51E2 as a potential therapeutic target and suggest that β-ionone or m6A inhibition may represent novel strategies for CRC treatment.

  View details for DOI 10.1016/j.phymed.2025.156599

  View details for PubMedID 40088737

• Quantitative microfluidic assay to measure neutralizing and total antibodies for SARS-CoV-2 SENSORS AND ACTUATORS B-CHEMICAL Bae, H., Lee, D., Kim, H., Jee, Y., Kim, J., Min, B., Park, Y., Seo, J., Lee, J., Lee, S., Kim, J., Jo, H., Na, K., Chung, S., Suh, I. 2024; 403

  View details for DOI 10.1016/j.snb.2023.135093

  View details for Web of Science ID 001148184100001