Research in Dr Rao's laboratory focusses on elucidating the molecular nature of ion transport mechanisms of epithelial cells in the gastrointestinal tract. This is crucial for understanding the basis of a variety of diseases ranging from infectious diarrheas to inflammatory bowel disease and cystic fibrosis (CF). We demonstrated that the rectum, in CF, exhibits impaired C1 transport in response to Ca-, cAMP- and cGMP-stimulation. We have established primary cultures of human colonic epithelial cells which exhibit hormone-sensitive C1 and Na transport. We are exploring whether the C1 transport is associated with the expression of mRNA and protein of the CF gene product, CFTR, or of other C1 channels. Epithelial cells possess multiple forms of the Na/H exchanger which appear to be involved in different functions. Using molecular cloning techniques we are trying to identify the different exchangers and by expressing them in exchanger deficient cell lines determine their function and regulation. Another Na transport mechanism is the Na/K/2C1 cotransporter which is differentially regulated in absorptive and secretory epithelia. We have developed an expression system in Xenopus oocytes for this cotransporter with a view to cloning it and studying its regulation. Our studies will elucidate the molecular basis of salt and water homeostasis.
Publications:
1. Suvitayavat. W., Palfrey, H.C., Haas, M., Dunham, P.B., Kalmar, F. and Rao, M.C. Characterization of the endogenous Na+-K+-2C1 cotransporter in Xenopus oocytes. Am. J. Physiology 266: Cell Physiology 35, C284-C292, 1994.
2. Bookstein, C., DePaoli, A.M, Xie, Y., Niu, P., Musch, M.W., Rao, M.C. and Chang, E.B. Na+/H+ exchangers, NHE-1 and NHE-3, of rat intestine: expression and localization. J. Clin. Invest. 93:106-113, 1994.
3. Rao, M.C., Bissonnette, G.B., Mahaffey, T. and Goldstein, J.L. Rectal epithelial expression of protein kinase A-phosphorylation of cystic fibrosis transmembrane conductance regulator. Gastroenterol . 106:890-898, 1994.
4. Sahi, J., Goldstein, J.L., Layden, T.J. and Rao, M.C.Cyclic AMP and phorbol ester regulated chloride permeabilities in primary cultures of human and rabbit colonocytes. Am. J. Physiology 266: Gastrointestinal and Liver Physiology 29: G846-G855, 1994.