Cytoskeletal Control of Gut Health and Disease

The intestinal epithelium forms one of the body’s largest and most dynamic barriers—sealing the gut from a vast array of microbes, dietary molecules, and immune triggers. This single-cell-layered tissue undergoes constant renewal and must maintain both mechanical integrity and selective permeability, which are critical for gut health. Disruption of this balance can lead to chronic inflammation and diseases such as Crohn’s disease and ulcerative colitis, and ultimately colorectal cancer.

Our lab investigates how cytoskeletal networks—specifically, the coordinated activity of septin filaments and non-muscle myosin II (NMII) motors—govern epithelial architecture, barrier function, and cell fate. These force-generating networks are dynamically remodeled during development, inflammation, and repair, and their dysfunction may be a key driver of disease.

Why is this exciting?

• Uncover novel roles for septins, the least understood cytoskeletal system, in gut epithelial biology.

• Use a rich toolbox of models, including fluorescent septin knockin mice, CRISPR-edited lines, and cytoskeletal biosensors.

• Leverage state-of-the-art intravital microscopy to visualize live cellular dynamics in the intact intestine at subcellular resolution—a rare and powerful window into real-time epithelial physiology.

• Address important biomedical questions relevant to IBD pathogenesis and epithelial regeneration.

• Join a collaborative and interdisciplinary environment at the interface of cell biology, biophysics, and mucosal immunology.

Current Projects

1. Septins as Organizers of Apical Junctional Architecture

We discovered that septins form a structured cytoskeletal scaffold at the apical junctional complex in intestinal epithelial cells. We are defining how septins coordinate the assembly of tight junctions and adherens junctions, control membrane curvature, and modulate barrier permeability using in vivo models, genetic tools, and mechanobiological assays.

2. Myosin Isoform-Specific Regulation of Intestinal Function

Using epithelial-specific knockouts and quantitative imaging, we are revealing distinct roles for NMII isoforms in organizing actomyosin networks and controlling epithelial tension. These studies are shedding light on how isoform-specific contractility tunes cell–cell adhesion and tissue mechanics under both physiological and pathological conditions, including aging .

3. Cytoskeletal Remodeling in Inflammation and Repair

We study how cytoskeletal dynamics are perturbed in inflammatory bowel disease using genetic mouse models, proteomics, and colitis induction paradigms. These approaches are helping us uncover how cytoskeletal remodeling influences barrier disruption, immune cell recruitment, and epithelial restitution during chronic inflammation.