Research

Endocrine–Immune–Metabolic Crosstalk in Human Disease

The Yi Lab investigates how endocrine signals reshape immune, metabolic, and neural networks across organs. We are particularly interested in how hormonal perturbations, tissue injury, exercise, sleep disruption, aging, and chronic metabolic stress alter inter-organ communication and drive systemic complications.

Our research is built on a translational framework: we start from clinically relevant human phenotypes, identify molecular and cellular signatures using multi-omics technologies, and test mechanistic hypotheses in experimental models. Through this approach, we aim to discover new disease mechanisms, biomarkers, and therapeutic targets for endocrine and metabolic disorders.

1. Thyroid Hormone Excess and γδ T-cell Immunometabolism

Thyroid hormone excess causes profound systemic changes, including weight loss, muscle wasting, bone loss, altered energy expenditure, and immune-metabolic remodeling. However, the immune mechanisms that mediate tissue complications of thyrotoxicosis remain incompletely understood.

Our laboratory studies how excess thyroid hormone reshapes γδ T-cell biology and how these immune changes contribute to muscle, bone, and metabolic dysfunction. We combine human samples collected before and after antithyroid treatment with mouse models of thyroid hormone excess to define immune-metabolic pathways involved in tissue damage and recovery.

Key questions

• How does thyroid hormone excess reprogram γδ T cells and other immune cell populations?

• Do IL-17-producing γδ T cells contribute to muscle wasting, bone loss, and systemic metabolic complications?

• Can immune-metabolic pathways be targeted to prevent tissue complications of thyrotoxicosis?

• How does endocrine treatment reverse or normalize immune-metabolic remodeling?

Approaches

• Human Graves’ disease cohorts before and after antithyroid therapy

• Mouse models of thyroid hormone excess

• γδ T-cell-focused immune profiling

• Single-cell RNA sequencing and TCR analysis

• ATAC-seq and transcriptomic analysis of immune-metabolic pathways

• Functional assessment of muscle, bone, and systemic metabolism

2. Sleep Science, Endocrine Rhythms, and Metabolic Health

Sleep is a fundamental regulator of endocrine and metabolic homeostasis. Hormonal disorders can disturb sleep architecture, circadian physiology, autonomic tone, brain metabolism, and systemic immune-metabolic balance. Conversely, sleep disruption may amplify metabolic dysfunction, inflammation, fatigue, sarcopenia, and cardiometabolic risk.

Our laboratory investigates how endocrine diseases, particularly thyroid hormone excess, alter sleep structure and brain–body metabolic communication. We aim to integrate clinical sleep phenotyping with endocrine assessment, wearable or polysomnographic monitoring, and molecular profiling to understand how sleep disruption contributes to systemic complications of metabolic disease.

Key questions

• How does thyroid hormone excess alter sleep architecture, sleep efficiency, and autonomic physiology?

• Are sleep disturbances in endocrine disease reversible after hormonal normalization?

• How do sleep disruption and circadian misalignment affect immune-metabolic remodeling?

• Can sleep-related physiological signatures predict fatigue, muscle dysfunction, metabolic risk, or treatment response?

• How does brain metabolic regulation interact with systemic endocrine and immune signals?

Approaches

• Human sleep studies in patients with endocrine and metabolic disorders

• Polysomnography and wearable sleep monitoring

• Pre- and post-treatment assessment of thyroid hormone excess

• Integration of sleep parameters with endocrine, metabolic, and inflammatory markers

• Collaboration with sleep medicine, neurology, and otolaryngology specialists

• Experimental models to study endocrine regulation of sleep and brain metabolism

3. Liver Injury, Fibrosis, Regeneration, and Cancer Metabolism

The liver is a central metabolic and immunological organ. Liver injury, fibrosis, regeneration, and hepatocarcinogenesis are regulated by complex interactions among hepatocytes, hepatic stellate cells, Kupffer cells, endothelial cells, lymphocytes, and extracellular matrix components.

Our laboratory investigates how metabolic pathways in hepatic stellate cells and the liver microenvironment regulate fibrosis, tissue repair, and tumor development. We are particularly interested in amino acid metabolism, alanine detoxification, creatine/guanidino metabolism, extracellular vesicles, and stromal-immune communication.

Key questions

• How do hepatic stellate cells regulate amino acid and nitrogen metabolism during liver injury?

• How does altered stellate cell metabolism influence fibrosis and hepatocarcinogenesis?

• What is the role of creatine and guanidino metabolism in liver injury repair and regeneration?

• How do stromal cells, immune cells, and hepatocytes communicate during fibrosis regression or tumor progression?

• Can liver metabolic pathways be therapeutically targeted to improve regeneration or suppress cancer development?

Approaches

• Mouse models of liver fibrosis, steatohepatitis, regeneration, and liver cancer

• Hepatic stellate cell-specific genetic models

• Stable isotope tracing and metabolic flux analysis

• Single-cell and spatial multi-omics

• Proteomics and metabolomics of liver tissue and circulating factors

• Functional validation of candidate metabolic pathways

4. Exercise Hormones and Extracellular Vesicle Multi-omics

Exercise induces rapid and coordinated changes in circulating metabolites, proteins, cytokines, hormones, and extracellular vesicles. These circulating mediators may explain how skeletal muscle communicates with distant organs and improves systemic metabolic health.

We study acute molecular responses to resistance and endurance exercise in humans. By profiling both plasma and extracellular vesicles at multiple time points, we aim to identify exercise-induced mediators that regulate metabolism, inflammation, muscle adaptation, and inter-organ communication.

Key questions

• What circulating molecules are acutely regulated by resistance versus endurance exercise?

• Are extracellular vesicles enriched for specific exercise-responsive proteins or metabolites?

• Can exercise-induced extracellular vesicles function as carriers of endocrine or immune-metabolic signals?

• Which molecular signatures distinguish immediate exercise stress from delayed recovery responses?

• Can exercise-responsive molecules be developed as biomarkers or therapeutic candidates?

Approaches

• Human exercise intervention studies

• Blood sampling before exercise, immediately after exercise, and during recovery

• Plasma proteomics and metabolomics

• Extracellular vesicle isolation and characterization

• EV proteomics and metabolomics

• Integrated multi-omics analysis of exercise-induced systemic signaling

5. Sarcopenia, Chronic Kidney Disease, and Translational Metabolism

Aging, chronic kidney disease, and metabolic disorders are frequently accompanied by sarcopenia, frailty, inflammation, and impaired physical function. These complications are not simply consequences of reduced activity; they reflect complex interactions among nutrient sensing, inflammation, mitochondrial function, endocrine signals, sleep disturbance, and tissue metabolism.

Our laboratory investigates the molecular basis of sarcopenia and metabolic dysfunction in chronic disease. We use clinical phenotyping and multi-omics approaches to identify biomarkers, mechanisms, and intervention strategies for improving muscle health and metabolic resilience.

Key questions

• What molecular signatures distinguish sarcopenia from preserved muscle function in chronic disease?

• How do chronic kidney disease and systemic inflammation alter muscle metabolism?

• Can circulating proteomic or metabolomic markers predict muscle quality, function, or treatment response?

• How do nutrition, exercise, and sleep influence metabolic and functional outcomes?

• Which pathways can be targeted to prevent frailty and muscle deterioration?

Approaches

• Human cohorts with detailed body composition and functional assessment

• CT-based muscle quality analysis

• Plasma proteomics and metabolomics

• Exercise and nutritional intervention studies

• Mouse models of chronic kidney disease and metabolic stress

• Biomarker discovery and translational validation

Enabling Technologies

To understand complex endocrine–immune–metabolic networks, we integrate multiple experimental and computational platforms.

Human translational studies

We design clinically grounded studies using patient samples, intervention cohorts, sleep studies, and disease-specific phenotyping to generate biologically meaningful hypotheses.

Single-cell and spatial multi-omics

We use single-cell RNA sequencing, immune repertoire analysis, spatial transcriptomics, and spatial metabolomics to map cellular interactions within tissues.

Proteomics and metabolomics

We profile proteins and metabolites in plasma, tissues, and extracellular vesicles to identify systemic mediators of disease and adaptation.

Sleep and physiological phenotyping

We integrate polysomnography, wearable monitoring, endocrine testing, autonomic physiology, and metabolic phenotyping to study brain–body communication in endocrine and metabolic disease.

Extracellular vesicle biology

We study extracellular vesicles as carriers of inter-organ communication, particularly in exercise, metabolic disease, and tissue injury.

Mouse disease models

We use genetic and dietary mouse models to test causal mechanisms in endocrine, liver, kidney, muscle, brain, and metabolic disease.

Therapeutic targeting

Our long-term goal is to translate mechanistic discoveries into therapeutic strategies that improve tissue repair, metabolic health, sleep quality, and healthy aging.

Research Vision

Endocrine diseases are systemic diseases. Hormones influence not only classical target organs but also immune cells, stromal cells, skeletal muscle, bone, liver, kidney, brain, and sleep–wake physiology. By defining how endocrine signals interact with immune, metabolic, and neural networks, the Yi Lab aims to uncover new mechanisms of human disease and develop strategies for precision metabolic medicine.