|
|
CHRISTIAN LYTLE, PH.D.Associate Professor of Biomedical Sciences
Ph.D., Duke University
Email: ' );
//-->
This email address is being protected from spam bots, you need Javascript enabled to view it
">
This email address is being protected from spam bots, you need Javascript enabled to view it
| | | Research Summary
Our research strives to understand the ion transport processes that underlie fluid and electrolyte secretion in the gastrointestinal tract, the mechanisms by which they are regulated, and how they might be altered in disease. The intestinal epithelium is perpetually renewed through the controlled proliferation and orderly migration of its principal cell lineages, and therefore the position of each cell within the migratory stream of the crypt-villus axis corresponds to its stage of maturation. Our general approach is to first delineate the spatial expression of ion transporters by epithelial cells within this migratory stream using immunohistochemical and confocal imaging techniques. We are particularly interested in how these expression profiles change hour by hour as the epithelium renews itself through proliferation, migration and apoptosis/exfoliation. We then employ an array of physiological techniques (flux assays, Ussing analysis, time-lapse spectrofluorometric imaging), and experimental models (transgenic mice, excised epithelial sheets, isolated glands or individual cells) to define the functional consequences of physiological or pathophysiological alterations on the intestine’s capacity for secretion, absorption, protection, and adaptation.
|  | Another longstanding interest is gastric acid secretion. Although it is now axiomatic that parietal cells secrete HCl, a growing body of evidence indicates that these cells undergo major morphological, biochemical, and functional changes as they migrate down the gastric gland. To clarify the biochemical nature and physiological purpose of this transformation, we are using immunocytochemical methods to map migration-associated alterations in secretory machinery, along with microscopic techniques to visualize regional differences in proton, chloride, and fluid transport within different segments of a single gastric gland.
| We are also exploring the pathophysiological consequences of epithelial remodeling in inflammatory bowel disease (IBD). A critical gap in our understanding of IBD, and the diarrhea associated with it, is the causal relationships between mucosal inflammation and intestinal epithelial barrier and transport function.
A third project, conducted in collaboration with Dr. Katie DeFea (UCR), explores the distribution and function of protease-activated receptor-2 (PAR-2) in the gastrointestinal tract. We have discovered that the main pool of PAR-2 in intestinal epithelial cells is physically associated with the apical junctional complex, a highly dynamic multifunctional complex that is critical to virtually all epithelial functions. Migration of the intestinal epithelial cell from the crypt base to the surface/villus is accompanied by a striking redistribution of PAR-2; interestingly, the observed redistribution from apical junctional complex to lateral membrane is topologically correlated with the migration-dependent reconfiguration of the epithelial cell from secretory to absorptive function.
Selected Publications
McDaniel, N., A.J. Pace, S. Spiegel, R. Engelhardt, B.H. Koller, U. Seidler, C. Lytle (2005) Role of Na-K-2Cl cotransporter-1 in gastric secretion of nonacidic fluid and pepsinogen. Am. J. Physiology: Gastrointest Liver Physiol 289:G550-G560.
Lytle, C. T.J. Tod, K.T. Vo, J.W. Lee, R.D. Atkinson, and D.S. Straus (2005). The PPARg ligand rosiglitazone delays the onset of inflammatory bowel disease in mice with interleukin 10 deficiency. Inflammatory Bowel Disease 11:231-243.
Wang, X.F., C. Lytle, and P..M. Quinton (2005) Predominant constitutive CFTR conductance in small airway. Respiratory Research 6:1-12.
Lytle, C., and T.J. McManus (2002) Coordinate modulation of Na-K-2Cl cotransport and K-Cl cotransport by cell volume and chloride. Am. J. Physiol. 283:C1422-C1431.
McDaniel, N., and C. Lytle (1999) Parietal cells express high levels of Na-K-2Cl cotransporter on migrating into the gastric gland neck. Am. J. Physiol. 276: G1273-G1280.
Lytle, C., T.J. McManus and M. Haas. (1998). A model of Na-K-2Cl cotransport based on ordered ion binding and glide symmetry. Am. J. Physiol. 274: C299-C309.
Lytle, C. (1998). A volume-sensitive protein kinase regulates the Na-K-2Cl cotransporter in duck red cells. Am. J. Physiol. 274: C1002-C1010.
|
|
|
People 
