About

Michael Lee is a 2026 SCiLL Senior Fellow in Public Leadership at the School of Civic Life and Leadership. He is recognized as a Visiting Fellow at the school, which is part of the University of North Carolina. His role involves engaging in public leadership initiatives and contributing to the school's mission of fostering civic life and leadership. Further details about his research focus, background, or key contributions are not provided in the available page text.

Research topics

• Biology
• Cell biology
• Genetics
• Medicine
• Chemistry

Selected publications

• Editorial: External factors influencing stem cells’ pluripotency, senescence, and differentiation

  Frontiers in Cell and Developmental Biology · 2025-11-07

  editorialOpen accessSenior authorCorresponding

  12 molecules, Reprogramming, Regenerative Medicine. 13 14Stem cells have the unique capacities for self-renewal and differentiation into multiple types 15 of functional cells, which are critical for regenerative medicine and tissue engineering (Ireland 16 and Simmons, 2015). Their fate, such as whether they self-renew, differentiate, or enter 17 senescence, is tightly regulated not only by intrinsic genetic and epigenetic factors but also 18 by a complex array of extrinsic factors. In particular, external factors, including the 19 microenvironment, receptor-ligand interactions, and mechanical forces, play critical roles in 20 maintaining stem cell pluripotency, directing differentiation, and preventing or inducing 21 senescence (Zhang et al., 2022;Sun et al., 2023). Aberrant regulation of these extrinsic factors 22 often leads to the loss of normal stem cells and other functional cells, or promotes the 23 formation of unwanted cells, such as cancer stem cells or malignant cancer cells (Ponomarev 24 et al., 2022). Another group of studies emphasizes how external cues direct stem cell differentiation 52 toward specific lineages. Zhang et al. (2025)

  PublisherOA PDFDOI

• Comparative toxicity of eleven bisphenol analogs in the nematode Caenorhabditis elegans

  Toxicology Letters · 2025-04-24 · 3 citations

  article
  PublisherDOI

• 6-PPD induces mitochondrial dysfunction and reduces healthspan and lifespan through SKN-1 in Caenorhabditis elegans

  Journal of Hazardous Materials · 2025-10-31 · 2 citations

  articleOpen access

  The synthetic antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6-PPD) is widely used in rubber products, but its toxicity in non-aquatic animals remains poorly understood. We investigated 6-PPD toxicity in mouse embryonic fibroblasts (MEFs) and Caenorhabditis elegans (C. elegans). In MEFs, 6-PPD caused dose-dependent increases in cell death, apoptosis, and mitochondrial dysfunction, along with elevated reactive oxygen species (ROS). In C. elegans, 6-PPD exposure led to higher mortality, delayed development, reduced reproduction, and shortened lifespan. Mitochondrial impairment, increased ROS, decreased mobility, and weakened stress tolerance were also observed. High-performance liquid chromatography (HPLC) analysis detected trace amounts of 6-PPD in C. elegans, whereas 6-PPD Quinone (6-PPDQ) was not detected within the analytical range. Furthermore, we found that 6-PPD upregulated the conserved transcription factor skinhead-1 (SKN-1/Nrf2) transcription factor. While SKN-1 was necessary for the reduced lifespan and early mortality caused by 6-PPD exposure, its loss failed to prevent the mitochondrial defects induced by 6-PPD exposure. Notably, SKN-1 gain-of-function mutations under basal conditions impaired mitochondrial function, and 6-PPD exposure further exacerbated these defects. These findings indicate that 6-PPD disrupts mitochondria through both SKN-1-dependent and SKN-1-independent mechanisms. Overall, our study demonstrates that 6-PPD impairs development, reproduction, healthspan, and lifespan through the SKN-1/Nrf2 pathway, with mitochondrial dysfunction mediated by both SKN-1/Nrf2-dependent and independent mechanisms.

  PublisherDOI

• Inhalation exposure to a tire-derived pollutant (6-PPD) triggers lung injury and mitochondrial dysfunction in mice

  Ecotoxicology and Environmental Safety · 2025-11-01 · 1 citations

  articleOpen access

  N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6-PPD)—a commonly used rubber antioxidant—is primarily released into the environment through tire wear particles, raising concerns about its potential respiratory health effects. However, little is known of its direct effects. This study investigated the pulmonary toxicity of 6-PPD in mice administered 5 or 10 mg/kg via intratracheal instillation for 7 or 14 days. No treatment-related mortality or significant changes in body weight were observed. However, lung weight significantly increased in all 6-PPD-treated groups, indicating lung tissue alterations. Bronchoalveolar lavage fluid analysis revealed dose-dependent increases in inflammatory cells, including macrophages, lymphocytes, neutrophils, and eosinophils, suggesting both acute and sustained inflammation. Furthermore, pro-inflammatory cytokines, including IL-6 and TNF-alpha, were significantly elevated, confirming a robust inflammatory response. Histopathological evaluation showed inflammatory infiltration, foamy alveolar macrophages, bronchial epithelial degeneration, and granulomatous inflammation, confirming 6-PPD-induced pulmonary injury. Mitochondrial protein expression analysis demonstrated that 6-PPD drives increased mitochondrial stress, leading to both mitophagy and autophagy. This stress was functionally supported by a notable reduction in Complex I activity and a corresponding decrease in cellular ATP levels, highlighting severe mitochondrial dysfunction. These findings demonstrate that 6-PPD induces considerable pulmonary inflammation (IL-6/TNF-alpha), histopathological alterations, and mitochondrial dysfunction (Complex I activity and ATP). The disruption of mitochondrial homeostasis may also contribute to sustained oxidative stress and chronic lung inflammation. These results highlight the potential respiratory risks associated with environmental exposure to 6-PPD. Although the doses used in this study exceed typical environmental levels, our results could provide a relevant model for high-level human occupational exposures to 6-PPD in humans. • 6-PPD exposure induces pulmonary toxicity in mice following intratracheal instillation. • Lung weight was significantly increased in all 6-PPD-treated groups. • Inflammatory cells and pro-inflammatory cytokines (IL-6, TNF-alpha) rose in BALF (dose-dependent). • 6-PPD drives increased mitochondrial stress, causing mitophagy and autophagy. • 6-PPD induces considerable pulmonary inflammation and mitochondrial dysfunction.

  PublisherDOI

• Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies

  Frontiers in Cell and Developmental Biology · 2025-03-03 · 4 citations

  reviewOpen accessSenior authorCorresponding

  Pluripotent stem cells (PSCs) possess the extraordinary capability to differentiate into a variety of cell types. This capability is tightly regulated by epigenetic mechanisms, particularly histone modifications. Moreover, the reprogramming of somatic or fate-committed cells into induced pluripotent stem cells (iPSCs) largely relies on these modifications, such as histone methylation and acetylation of histones. While extensive research has been conducted utilizing mouse models, the significance of histone modifications in human iPSCs is gaining increasing recognition. Recent studies underscore the importance of epigenetic regulators in both the reprogramming process and the regulation of cancer stem cells (CSCs), which are pivotal in tumor initiation and the development of treatment resistance. This review elucidates the dynamic alterations in histone modifications that impact reprogramming and emphasizes the necessity for a balance between activating and repressive marks. These epigenetic marks are influenced by enzymes such as DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). Furthermore, this review explores therapeutic strategies aimed at targeting these epigenetic modifications to enhance treatment efficacy in cancer while advancing the understanding of pluripotency and reprogramming. Despite promising developments in the creation of inhibitors for histone-modifying enzymes, challenges such as selectivity and therapy resistance continue to pose significant hurdles. Therefore, future endeavors must prioritize biomarker-driven approaches and gene-editing technologies to optimize the efficacy of epigenetic therapies.

  PublisherOA PDFDOI

• Reviewer #2 (Public Review): Mitochondrial stress in GABAergic neurons non-cell autonomously regulates organismal health and aging

  2024-05-14

  peer-reviewOpen access

  Mitochondrial stress within the nervous system can trigger non-cell autonomous responses in peripheral tissues. However, the specific neurons involved and their impact on organismal aging and health have remained incompletely understood. Here, we demonstrate that mitochondrial stress in γ-aminobutyric acid-producing (GABAergic) neurons in Caenorhabditis elegans (C. elegans) is sufficient to significantly alter organismal lifespan, stress tolerance, and reproductive capabilities. This mitochondrial stress also leads to significant changes in mitochondrial mass, energy production, and levels of reactive oxygen species (ROS). DAF-16/FoxO activity is enhanced by GABAergic neuronal mitochondrial stress and mediates the induction of these non-cell-autonomous effects. Moreover, our findings indicate that GABA signaling operates within the same pathway as mitochondrial stress in GABAergic neurons, resulting in non-cell-autonomous alterations in organismal stress tolerance and longevity. In summary, these data suggest the crucial role of GABAergic neurons in detecting mitochondrial stress and orchestrating non-cell-autonomous changes throughout the organism.

  PublisherDOI

• Reviewer #1 (Public Review): Mitochondrial stress in GABAergic neurons non-cell autonomously regulates organismal health and aging

  2024-05-14

  peer-reviewOpen access

  Mitochondrial stress within the nervous system can trigger non-cell autonomous responses in peripheral tissues. However, the specific neurons involved and their impact on organismal aging and health have remained incompletely understood. Here, we demonstrate that mitochondrial stress in γ-aminobutyric acid-producing (GABAergic) neurons in Caenorhabditis elegans (C. elegans) is sufficient to significantly alter organismal lifespan, stress tolerance, and reproductive capabilities. This mitochondrial stress also leads to significant changes in mitochondrial mass, energy production, and levels of reactive oxygen species (ROS). DAF-16/FoxO activity is enhanced by GABAergic neuronal mitochondrial stress and mediates the induction of these non-cell-autonomous effects. Moreover, our findings indicate that GABA signaling operates within the same pathway as mitochondrial stress in GABAergic neurons, resulting in non-cell-autonomous alterations in organismal stress tolerance and longevity. In summary, these data suggest the crucial role of GABAergic neurons in detecting mitochondrial stress and orchestrating non-cell-autonomous changes throughout the organism.

  PublisherOA PDFDOI

• C. elegans Germline as Three Distinct Tumor Models

  Biology · 2024-06-08 · 2 citations

  reviewOpen accessSenior authorCorresponding

  Tumor cells display abnormal growth and division, avoiding the natural process of cell death. These cells can be benign (non-cancerous growth) or malignant (cancerous growth). Over the past few decades, numerous in vitro or in vivo tumor models have been employed to understand the molecular mechanisms associated with tumorigenesis in diverse regards. However, our comprehension of how non-tumor cells transform into tumor cells at molecular and cellular levels remains incomplete. The nematode C. elegans has emerged as an excellent model organism for exploring various phenomena, including tumorigenesis. Although C. elegans does not naturally develop cancer, it serves as a valuable platform for identifying oncogenes and the underlying mechanisms within a live organism. In this review, we describe three distinct germline tumor models in C. elegans, highlighting their associated mechanisms and related regulators: (1) ectopic proliferation due to aberrant activation of GLP-1/Notch signaling, (2) meiotic entry failure resulting from the loss of GLD-1/STAR RNA-binding protein, (3) spermatogenic dedifferentiation caused by the loss of PUF-8/PUF RNA-binding protein. Each model requires the mutations of specific genes (glp-1, gld-1, and puf-8) and operates through distinct molecular mechanisms. Despite these differences in the origins of tumorigenesis, the internal regulatory networks within each tumor model display shared features. Given the conservation of many of the regulators implicated in C. elegans tumorigenesis, it is proposed that these unique models hold significant potential for enhancing our comprehension of the broader control mechanisms governing tumorigenesis.

  PublisherOA PDFDOI

• Increased Risk of Acute Exacerbations and Mortality in Short-acting Beta-agonist Overuse Patients: A Systematic Review and Meta-analysis

  2024-04-30

  review
  PublisherDOI

• Mitochondrial stress in GABAergic neurons non-cell autonomously regulates organismal health and aging

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-03-25

  preprintOpen access

  Abstract Mitochondrial stress within the nervous system can trigger non-cell autonomous responses in peripheral tissues. However, the specific neurons involved and their impact on organismal aging and health have remained incompletely understood. Here, we demonstrate that mitochondrial stress in γ-aminobutyric acid-producing (GABAergic) neurons in Caenorhabditis elegans ( C. elegans ) is sufficient to significantly alter organismal lifespan, stress tolerance, and reproductive capabilities. This mitochondrial stress also leads to significant changes in mitochondrial mass, energy production, and levels of reactive oxygen species (ROS). DAF-16/FoxO activity is enhanced by GABAergic neuronal mitochondrial stress and mediates the induction of these non-cell-autonomous effects. Moreover, our findings indicate that GABA signaling operates within the same pathway as mitochondrial stress in GABAergic neurons, resulting in non-cell-autonomous alterations in organismal stress tolerance and longevity. In summary, these data suggest the crucial role of GABAergic neurons in detecting mitochondrial stress and orchestrating non-cell-autonomous changes throughout the organism.

  PublisherOA PDFDOI

Recent grants

• Role of PUF-8/Pumilio in GLP-1/Notch-Mediated Germline Proliferation in C. elegans

  NIH · $367k · 2015–2018

• Action Mechanisms of Resveratrol in Somatic Longevity and Reproductive System

  NIH · $459k · 2018–2023

• Regulatory Mechanism for Cellular Dedifferentiation in C. elegans Germline

  NSF · $600k · 2022–2027

Frequent coauthors

• Adam S. Asch

  Oklahoma State University Oklahoma City

  43 shared

• Mohammad A. Alfhili

  King Saud University

  42 shared

• Dong Seok

  Korea University of Science and Technology

  39 shared

• Judith Kimble

  University of Wisconsin–Madison

  32 shared

• Dong Suk Yoon

  32 shared

• Boyoung Joung

  Gangnam Severance Hospital

  15 shared

• Jin Woo Lee

  Yonsei University

  15 shared

• Jae‐Sun Uhm

  Gangnam Severance Hospital

  14 shared

Education

• Ph.D, Biochemistry

  Yonsei University

  2003

Awards & honors

• 2026 SCiLL Senior Fellow in Public Leadership