Intestinal epithelial cells (IECs), including enterocytes, goblet cells, Paneth cells, and enteroendocrine cells, continuously differentiate from intestinal stem cells (ISCs) located at the base of the crypts. IECs are fundamental to maintaining mucosal homeostasis by serving as a barrier that separates the internal environment from the external lumen, facilitating nutrient absorption, regulating immune responses through the production of cytokines and chemokines that recruit and activate immune cells, and interacting with the microbiota by secreting antimicrobial peptides (AMPs) to regulate microbial composition and prevent pathogen overgrowth. Dysregulation of IEC function can lead to a wide range of mucosal and systemic diseases, highlighting their critical role in both health and pathology. For example, in conditions such as Crohn's disease and ulcerative colitis, chronic inflammation damages IECs, disrupting barrier function and leading to increased intestinal permeability or ‘leaky gut’. Additionally, mutations in IECs, particularly in ISCs, can result in uncontrolled cell proliferation and the development of colorectal cancer.
Dr. Pan’s lab employs a multidisciplinary approach, integrating microbiology, molecular biology, cell biology, immunology, and pathology to investigate several key questions:
1. How intestinal epithelial cells respond to microbial, metabolic and neural cues, and how they interact with diverse cell types to convey physiological signals.
2. How dysregulation of these interactions can lead to a range of intestinal and systemic diseases, such as inflammation, cancer, and infections.
3. How to design therapeutic strategy targeting the interface of these interactions.
Another arm of their research aims to understand how intestinal epithelial cells integrate the environment signals and undergo dynamic epigenetic changes to repair and restore the barrier function during stress or injury. Our group focuses on the roles of histidine methylation, a less-studied posttranslational modification, in regulating intestinal epithelial barrier function and its implications in intestinal pathologies such as inflammation and cancer.