The PI is an Assistant Professor of Medicine in the Division of Digestive Diseases at the University of Cincinnati College of Medicine. He received his postdoctoral research training under the supervision of Drs. John Dobbins and Peter Aronson of the Depts. of Medicine and Physiology at Yale University. This work culminated in the description of a new anion exchanger and formed the basis for 3 manuscripts (2 papers - Am J Physiol, in press). Since moving to Cincinnati, the PI has performed studies of folate transport by intestinal brush border membrane vesicles which defined the driving forces for the uptake of dietary folate (J Clin Invest, in press). The proposed research is aimed at achieving a better understanding of the cellular mechanisms and molecular biology of intestinal solute transport. The application identifies 3 major areas of investigation. First, studies in intestinal brush border and basolateral membrane vesicles will deal with the driving forces for anion transport (folate; bile acids) and test the hypothesis that the outwardly-directed OH- gradient across the brush border membrane (manifested in vivo by the brush border """"""""acid microclimate"""""""") is a physiologically important gradient for uphill solute transport. Second, we will attempt to isolate the brush border membrane protein that mediates folate transport. This would permit the raising of specific antibodies or nucleotide probes that could be used to clone the gene encoding the folate transport protein. Finally, since the transmembrane pH gradient reflects the acid microclimate which in turn may result from the activity of the Na+:H+ exchanger, we will also study the role of polyamines in modulating the activity of this exchanger. The environment at the University of Cincinnati is ideally conducive to the further growth of the PI. The Primary Sponsor, Dr. Bennett L. Blitzer, is an established investigator in the field of hepatic ion transport with considerable experience in the purification of plasma membrane vesicles and performance of vesicle transport studies. The Secondary Sponsor, Dr. Ralph A. Giannella, is an authority in the general area of intestinal secretion and has experience in membrane protein isolation. Dr. Earl Wallick will also assist in membrane protein isolation/sequencing and Dr. John Hutton will collaborate in gene cloning studies. The PI's time will be protected in order for him to devote 75% of his efforts to the project with 6 months in the 3rd year to be spent in Dr. Hutton's laboratory learning the techniques of molecular genetics.
