Most of my research career has been devoted to the study of pacemaker and neuro-effector mechanisms in visceral smooth muscles. My group has extensive experience isolating and studying basic mechanisms of interstitial cells and investigating the physiological regulation provided by unique cell types in smooth muscle tissues. For example, we were the first to isolate and record from interstitial cells of Cajal and PDGFR+ cells in the GI tract and bladder. We have developed cell-specific markers, exploiting immunological techniques, genetic engineering and endocytosis mechanisms, to make it possible to identify specific types of cells in complex tissues and mixed cell dispersions. We pioneered the use of flow cytometry and fluorescence-activated cell sorting to quantify relative numbers of cells, purify specific populations of cells dispersed from GI muscles and collect cells from these tissues for genome-wide expression analyses. A broad range of physiological and morphological techniques has been used to evaluate structure, distribution, cell-to-cell interactions and functions of interstitial cells. Now we are investigating the question of the basic pacemaker mechanisms in gastric and colonic ICC, using optogenetic techniques and cell-specific expression of Ca2+ sensors, and powerful confocal imaging techniques and analyses. These experiments are producing an unprecedented evaluation of the behaviors and mechanisms of different classes of gastric and colonic ICC and providing understanding of the functions of these cells in motor patterns.
