Sleep and Performance Research Center

Influence of Circadian Rhythms on Physiology, Diseases, and Therapeutic Interventions

YOOL LEE, PH.D.

Areas of Interest

Circadian rhythms, sleep deprivation and disorders, cancer evolution, neurodegenerative diseases, chronotherapy

Research Scope

Circadian clocks represent cellular timing systems that generate 24-hour biological rhythms, a phenomenon conserved across diverse life forms, from unicellular organisms to humans. The internal body clock harmonizes with various environmental and metabolic stimuli, such as light and food, orchestrating daily behavioral rhythms (e.g., sleep/wake and feeding cycles), physiological patterns (e.g., body temperature, hormonal and immune systems), and cellular processes (e.g., metabolic and cell cycle pathways). In modern society, factors that disrupt circadian rhythms, including sleep deprivation, jet lag, shift work, and aging, are recognized to increase susceptibility to metabolic disorders (e.g., cancers) and neurodegenerative conditions (e.g., Alzheimer’s disease). Conversely, these pathological disorders increasingly reveal their impact on disrupting the sleep-wake cycle and circadian physiology. Therefore, a detailed understanding of the regulatory pathways of the circadian clock and their intricate interplay with various disease processes is crucial for the prevention and treatment of disorders associated with circadian dysregulation.

Research Focus

Our laboratory research centers around three primary areas: (1) Understanding the biological mechanisms of circadian physiology and behaviors in animal and cellular models; (2) Investigating the molecular and cellular impact of circadian disruptions on tumor heterogeneity, tumor microenvironment, and metastatic progression in human and mouse cancer models; (3) Translational applications of circadian physiology for the treatment of cancer and aging-related pathologies using nutritional, metabolic, and pharmacological interventions.

Staff

Prajakta Vaishampayan, M.S. (Scientific Assistant)

Approaches Used

Genetic and molecular analysis: CRISPR/Cas9 genome editing, RNAi knock-down, PCR-based molecular DNA cloning, quantitative real-time PCR, RNA sequencing analysis
Biochemical analysis: Western blot, Immunoprecipitation (IP), Chromatin immunoprecipitation (ChIP) analysis
2D/3D cell and tissue culture analysis: 1) Förster Resonance Energy Transfer (FRET) and Biomolecular Fluorescence Complementation (BiFC) assays for live cell imaging of protein-protein interactions; 2) Time-lapse cell cycle analysis using Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) system; 3) Real-time fluorescence imaging of the dynamic evolution of cancer cells, employing fluorescence reporters for Cancer Stem Cell (CSC) in both monolayer cells and 3D cultured tumor spheroids; 4) Real-time bioluminescence recording monitors of circadian rhythms using clock reporter cells or transgenic mouse tissues; 5) Fluorescence-Activated Cell Sorting (FACS) and immunohistochemistry (IHC) analyses with mouse xenografted tumors
Metabolic analysis: Metabolic Flux Analysis to measure cellular energy metabolisms such as glycolysis and mitochondrial respiration, and oxidative stress levels
Pharmacological analysis: High-throughput measurement of dose and time-dependent efficacy of therapeutic agents using an automatic muli-mode plate reader
In vivo imaging analysis: Live-animal imaging analysis of circadian bioluminescence reporter mice using IVIS Spectrum imaging System
Behavioral analysis: Long-term monitoring of daily locomotor activity of mice in circadian chamber instruments under various settings of circadian environments