Epithelial Epigenetics

Our Science

Epithelial tissues form the body's primary interface with the outside world. Every day they encounter ultraviolet radiation, microbes, pollutants, dietary metabolites, mechanical injury, and inflammation, yet they maintain remarkable stability while retaining the ability to rapidly repair and adapt. A central question in our laboratory is:

How do epithelial tissues sense, adapt to, and remember environmental experiences, and how do these adaptations influence health and disease?

The Capell Laboratory studies how chromatin and enhancer regulatory mechanisms encode epithelial cell identity, tissue adaptation, and disease susceptibility. We investigate how environmental exposures and intrinsic cellular programs reshape chromatin landscapes to regulate differentiation, regeneration, immunity, aging, and cancer. By combining human genomics, genetically engineered mouse models, functional epigenetics, and cutting-edge single-cell and spatial genomic technologies, we seek to uncover fundamental principles of epithelial biology and translate these discoveries into new therapies for inflammatory diseases and epithelial cancers.

Our Research

Environmental Adaptation & Epigenetic Memory

Epithelial tissues are continuously shaped by environmental exposures throughout life. While many responses to environmental stress are transient, increasing evidence suggests that epithelial cells can retain long-lasting molecular memories of prior exposures through persistent changes in chromatin organization and enhancer activity.

Our laboratory investigates how environmental factors—including ultraviolet radiation, inflammation, metabolism, and the broader exposome—reshape chromatin landscapes to establish persistent epithelial cell states. We are particularly interested in understanding how these adaptive responses become maladaptive over time, promoting chronic inflammation, impaired tissue repair, aging, and cancer. A major goal of our research is to determine whether these persistent chromatin states can be therapeutically reprogrammed to restore healthy tissue function.

Central question: How do epithelial tissues remember environmental experiences, and can these memories be therapeutically rewritten?

Chromatin Regulation of Epithelial Cell States

Cell identity is maintained through highly coordinated gene regulatory networks controlled by chromatin organization and enhancer activity. Our laboratory studies the epigenetic mechanisms that establish, preserve, and remodel epithelial cell states during development, homeostasis, regeneration, and disease.

Using genetic and pharmacologic approaches, we investigate how chromatin regulators—including KMT2D/MLL4, UTX/KDM6A, LSD1/KDM1A, and related pathways—coordinate epithelial differentiation, tissue regeneration, retinoid signaling, and stress-responsive transcriptional programs. These studies seek to define fundamental principles governing epithelial plasticity and how disruption of enhancer regulation contributes to disease.

Central question: How do chromatin and enhancer networks establish and preserve epithelial cell identity?

Epithelial Immunity, Metabolism & Cancer

Epithelial tissues actively communicate with surrounding immune, stromal, and metabolic environments to coordinate tissue homeostasis. Rather than serving as passive barriers, epithelial cells direct immune responses, regulate tissue repair, and influence susceptibility to cancer.

Our research examines how chromatin remodeling integrates immune signaling, lipid metabolism, ferroptosis, and environmental stress to regulate epithelial–immune interactions during tissue injury and tumor development. We also investigate how inherited and acquired alterations in chromatin regulators, including sex chromosome-linked epigenetic regulators and mutations commonly observed in squamous cell carcinoma, shape disease susceptibility and tumor evolution.

By integrating spatial biology with functional genomic approaches, we seek to understand how epithelial chromatin states regulate tissue microenvironments and anti-tumor immunity.

Central question: How do epithelial chromatin states coordinate immunity, metabolism, and cancer development?

Epigenetic Therapeutics

One of the most exciting aspects of epigenetic regulation is that chromatin states are inherently dynamic and potentially reversible. Our long-term goal is to translate mechanistic discoveries in chromatin biology into novel therapeutic strategies for epithelial diseases.

Our laboratory develops and evaluates pharmacologic and genetic approaches that reprogram disease-associated chromatin states to restore epithelial differentiation, improve tissue repair, enhance anti-tumor immunity, and suppress carcinogenesis. By understanding how chromatin regulates epithelial adaptation and tissue memory, we hope to develop therapies that prevent disease before irreversible tissue damage occurs.

Central question: Can chromatin be therapeutically reprogrammed to restore healthy epithelial tissue states?

Our Approach

Our research integrates human patient specimens, primary epithelial cell models, genetically engineered mouse models, and organotypic culture systems with state-of-the-art genomic technologies. We employ single-cell and spatial approaches, as well as functional genetic perturbation to investigate epithelial biology across multiple scales. This multidisciplinary approach enables us to connect molecular mechanisms with tissue physiology and human disease while translating fundamental discoveries toward new therapeutic strategies.

Join Our Team

We are always interested in recruiting outstanding graduate students, postdoctoral fellows, clinical fellows, and collaborators who are passionate about epithelial biology, chromatin regulation, genomics, and translational science. If you are interested in joining the laboratory or collaborating with us, we would be delighted to hear from you.