Our research interests revolve around the molecular, cellular and translational biology of the gastrointestinal neuromuscular system, with particular focus on interstitial cells of Cajal (ICC).
ICC are evolutionarily conserved mesenchymal cells that generate electrical rhythmicity required for gut peristalsis, mediate nerve-muscle interactions and set smooth muscle membrane potential and tone. Loss of ICC leads to gastrointestinal motility disorders; and their neoplastic growth underlies gastrointestinal stromal tumors, the most common form of sarcoma.
Both groups of diseases lack curative therapy. Our current efforts are devoted to understanding the cell-intrinsic and microenvironmental mechanisms regulating postnatal turnover of ICC from local stem/progenitor cells, with particular focus on epigenetic control of gene transcription and receptor tyrosine kinase signaling.
Using isolated ICC precursors and animal models of diabetes, eating disorders, aging and gastrointestinal stromal tumors we study the mechanisms-of-action of drug candidates that could be developed into novel therapies for restoring normal ICC networks and making neoplastic ICC more sensitive to targeted cancer therapy.
We collaborate with several Mayo Clinic investigators through the Gastroenterology Research Unit, the Mayo Clinic Center for Individualized Medicine, the Enteric NeuroScience Program, the Mayo Clinic Center for Cell Signaling in Gastroenterology, and the Gastrointestinal Cancer Group of the Mayo Clinic Cancer Center.
Current research projects include the following:
- Epigenetic regulation of receptor tyrosine kinase gene expression in ICC precursors
- Epigenetic control of gene expression in the ICC/GIST microenvironment
- Role of membrane-to-nucleus signaling in stem cell maintenance and aging in the gastrointestinal neuromuscular system
- Molecular underpinnings of the relationship between caloric intake and gastrointestinal motor functions
- Novel therapeutic options targeting cancer stem cells in GIST
- Genomics and epigenomics of ICC