My laboratory studies ion-solute movements across cell membranes. Membrane transporters, particularly in the kidney, account for ~10% of mammalian genomes and 50% of current drug targets. We want to understand and exploit this portion of the genome. Thus, we clone mammalian, vertebrate and invertebrate transporter SLC (SoLute Carrier) cDNAs and express the SLC proteins in Xenopusfrog oocytes or mammalian cells. To study SLC clones, we functionally characterize the transporters using a range of strategies including electrophysiology, molecular biology, biochemistry, cell biology, whole organ, and integrative biological approaches. Generally, we examine five issues in each project: (a) genetics/gene structure, (b) transport physiology, (c) protein localization, (d) protein structure, (e) protein - protein interactions and (f) functional roles in animal models and implications for disease. Previous studies have used Drosophila to elucidate function in epithelia. Recently we have taken advantage of the zebrafish genetic model to gain insight into the function of mammalian genes critical for renal uptake of monocarboxylates (lactate, pyruvate, short chain fatty acids, ketoacids). Presently we have cloned and analyzed function of anion transporters in the Slc4 and Slc26 gene families as well as the newly discovered Na+ monocarboxylate transporters of the Slc5 gene family.
Our current projects fall into five major areas:
- Na+ coupled bicarbonate transporters (SLC4 gene family)
- Acid-base transport by the SLC26 gene family
- Na+ coupled monocarboxylate cotransporters (SLC5A8, SLC5A12)
- Divalent cation transport
- Related ion-solute transporters of evolutionarily distant organisms, e.g., insects, fish, bacteria