Basic Science Research
The mammalian gastrointestinal tract matures from a primitive tube into morphologically and functionally distinct regions during development. The mature small intestine functions in the digestion and absorption of ingested nutrients. Several of the hydrolases responsible for enzymatic nutrient digestion including lactase, sucrase-isomaltase, and maltase are expressed by the enterocyte, a specialized small intestinal epithelial cell derived from the gut endoderm cell lineage.
Maximal expression of several hydrolases is spatially restricted to distinct segments along the cephalo-caudal axis of the small intestine and is temporally regulated during postnatal maturation. Intestinal lactase, the hydrolase responsible for the digestion of lactose in milk, is expressed at highest levels in the jejunal segment of the small intestine shortly after birth and then declines dramatically just prior to weaning in most mammals.
Our research is directed towards defining the mechanisms regulating this spatial and temporal restriction of lactase gene expression during intestinal development. The overall goal is to relate these lactase control mechanisms to the broader pathways specifying acquisition of a small intestinal phenotype.
Research Spotlight: Zachary Sellers, MD, PhD
Cystic fibrosis (CF) is the most common lethal inherited disease in Caucasians and affects about 30,000 individuals in the U.S. The symptoms associated with CF are due to ineffective transport of chloride and bicarbonate ions from loss of CFTR channel activity. Studying CF combines my interest in ion channels and physiology, and allows me to examine how an ion channel defect can affect many tissues throughout the body. I am also privileged to work with a multi-disciplinary health care team and families that are dedicated to improving the clinical care for individuals with CF. I am driven by opportunities to meld basic science and clinical investigation with clinical interventions to find new ways to improve the health of those with CF.
In the intestines, loss of CFTR leads to intestinal obstruction, decreased intestinal pH, and nutrient malabsorption. My research in this area is focused on identifying means to restore defective bicarbonate secretion in the duodenum in an attempt to alleviate these symptoms. CFTR is central to duodenal bicarbonate secretion, however, we have identified targets that are able to stimulate bicarbonate secretion independent of CFTR in CF intestines. Using a combination of Ussing chamber, intestinal perfusion studies, and cell biology methods we are characterizing how these agents work in order to develop novel therapies for CF.
In addition to my work in CF, Dr. Cox and I are part of the INSPPIRE Consortium (INternational Study group for Pediatric Pancreatitis In search for a cuRE), which is longitudinally studying children with acute, acute recurrent, and chronic pancreatitis and is part of an NIH NIDDK and NCI-sponsored project with adult gastroenterology centers, “Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer.”