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My research interest is studying the roles of microRNAs (miRNAs) that control gut neuromuscular (motility) disorders. The gut is a vital organ for human survival: it is where food is digested, where nutrients are absorbed into the bloodstream, and where undigested waste moves through and leaves the body. This digestive process is achieved by the synchronized movement (motility) of gastrointestinal (GI) muscle, which mixes food and propels the digested content through the GI tract. Motility of GI muscle is controlled by three key cells: enteric nervous system (ENS), interstitial cells of Cajal (ICC), and smooth muscle cells (SMCs). ENS and ICC generate complex rhythmic motor behavior and spontaneous electrical slow waves, respectively, both of which control SMCs, the final effectors for muscle contraction and muscle relaxation. Developmental abnormalities and pathophysiological damage of these cells are directly linked to GI neuromuscular diseases such as Hirschsprung's disease, diabetic gastroenteropathy (DGEP), gastrointestinal stromal tumor (GIST), and chronic intestinal pseudo-obstruction (CIPO). All these motility diseases are thought to be developed from the remodeling of the smooth muscle in the GI tract, leading to abnormal growth (hypertrophy or tumor) or death (myopathy) of the cells. miRNAs are a new class of small RNAs that are known to be powerful regulators of gene expression during animal development. Our previous studies discovered that miRNAs regulate SMC growth and differentiation in the GI tract, which are required for the animals' survival. However, the cellular and molecular mechanisms underlying remodeling of the GI smooth muscle by miRNAs in motility disorders are largely unknown. We have currently generated several animal models with GI motility disorders (myopathy, hypertrophy, and diabetic gastroenteropathy) using: conventional cell-specific gene deletion (Dicer, Srf, and Dnmt1), inducible cell-specific gene deletion (Dicer, Srf, and Dnmt1), a congenital mutation (Edn3), a partial obstruction surgery on the small intestine, a conventional gene deletion (Lep), and a spontaneous gene mutation (TALLYHO/JungJ). In the animal models, SMCs or ICC are labeled with green fluorescent protein (GFP) (Fig. 1). We have developed cytometric techniques to isolate SMCs or ICC from the GFP mice using GFP, as well as non-GFP mice using cell specific surface markers. The GFP animal models are a powerful tool for studying the genetic, cellular, and functional changes in the motility disorders. Using these animal models, we seek to uncover novel mechanisms involving miRNAs that lead to the abnormal growth or loss of SMCs and ICC during the development of motility disorders. Identifying such mechanisms will aid not only in the development of a diagnostic tool for various neuromuscular diseases, but also of a therapeutic target that has the potential to reverse the genetic changes that are responsible for these pathological conditions, and thus possibly reverse some of the unwanted pathological changes that occur in these diseases.