Associate Professor of Internal Medicine and Adjunct Assistant Professor of Human Genetics
Ion Transport, Kinase, Drosophila, Kidney, Osmoregulation, Blood Pressure, Salt Sensitivity, Potassium, Sodium
Ion transport, the vectorial movement of ions across cell membranes, is a fundamental process that is essential to normal physiology and is perturbed in a variety of disease processes. In the kidney, epithelial ion transport regulates the concentration of ions, such as sodium and potassium, and determines extracellular volume and blood pressure. Kidney dysfunction can lead to perturbations in these regulatory processes, resulting in electrolyte disturbances, hypotension, or hypertension.
My laboratory uses the fruit fly Drosophila melanogaster as a model organism to study ion transport processes relevant to human physiology. Drosophila has a short life cycle, sophisticated genetics, and in many cases single gene representation of mammalian multi-gene families, simplifying analysis of pathways of interest. Our goal is to use to the fly to study ion transporters and channels that are conserved in humans, as well as the molecular mechanisms of regulation of these transporters and channels. One area of focus is the SLC12 family of cation-chloride transporters, such as the potassium-chloride cotransporter and the sodium-potassium-2 chloride cotransporter, and their regulation by WNK and SPAK/OSR1 kinases, which have been implicated in hypertensive disorders in humans. We are also studying potassium and chloride channels, which have also been implicated in several human disorders. We study these pathways in the fly renal (Malpighian) tubule and hindgut, in which epithelial ion transport is required for ionic and osmotic homeostasis. Our goal is to understand these transporters, channels and their regulation in greater mechanistic detail, identify new regulatory factors, and translate these insights into improved understanding of ion transport processes in health and disease.
- Pleinis JM, Norrell L, Akella R, Humphreys JM, He H, Sun Q, Zhang F, Sosa-Pagan J, Morrison DE, Schellinger JN, Jackson LK, Goldsmith EJ, Rodan AR (2021). WNKs are potassium-sensitive kinases. Am J Physiol Cell Physiol, 320: C703-C721.
- Talsness DM, Owings KG, Coelho E, Mercenne G, Pleinis JM, Partha R, Hope KA, Zuberi AR, Clark NL, Lutz CM, Rodan AR, Chow CY (2020). A Drosophila screen identifies NKCC1 as a modifier of NGLY1 deficiency. eLife, 9: e57831.
- Jonusaite S, Beyenbach KW, Meyer H, Paululat A, Izumi Y, Furuse M, Rodan AR (2020). The septate junction protein Mesh is required for epithelial morphogenesis, ion transport and paracellular permeability in the Drosophila Malpighian tubule. Am J Physiol Cell Physiol, 318: C675-C694
- Beyenbach KW, Schoene F, Breitsprecher LF, Tiburcy F, Furuse M, Izumi Y, Meyer H, Rodan AR, Paululat A (2020). The septate junction protein Tetraspanin 2A is critical to the structure and function of Malpighian tubules in Drosophila melanogaster. Am J Physiol Cell Physiol, doi: 10.1152/ajpcell.00061.2020 [Epub ahead of print].
- Rodan AR (2019) The Drosophila Malpighian tubule as a model for mammalian tubule function. Curr Opin Nephrol Hypertens doi: 10.1097/MNH.0000000000000521 [Epub ahead of print]
- Stenesen D, Moehlman AT, Schellinger JN, Rodan AR*, Krämer H (2019). The glial sodium-potassium-2-chloride cotransporter is required for synaptic transmission in the Drosophila visual system. Sci Rep, 9: 2475. *, co-corresponding author.
- Lakshmipathi J, Wheatley W, Kumar A, Mercenne G, Rodan AR, Kohan DE (2019). Identification of NFAT5 as a transcriptional regulator of the EDN1 gene in collecting duct. Am J Physiol Renal Physiol, 316: F481-F487
- Rodan AR (2019) Intracellular chloride: a regulator of transepithelial transport in the distal nephron. Curr Opin Neph Hypertens 28: 360-367
- Sun Q, Wu Y, Jonusaite S, Pleinis JM, Humphreys JM, He H, Schellinger JN, Akella R, Stenesen D, Krämer H, Goldsmith EJ, Rodan AR (2018). Intracellular chloride and scaffold protein Mo25 cooperatively regulate transepithelial ion transport through WNK signaling in the Malpighian tubule. J Am Soc Nephrol, 29: 1449-1461
- Rodan AR(2018) WNK-SPAK/OSR1 signaling: lessons learned from an insect renal epithelium. Am J Physiol Renal Physiol doi: 10.1152/ajprenal.00176.2018. [Epub ahead of print]
- Rodan AR (2017) Potassium: friend or foe? Pediatr Nephrol 32: 1109-1121
- Cheng CJ, Rodan AR and Huang CL. (2017) Emerging targets of diuretic therapy. Clinical Pharmacology & Therapeutics, doi: 10.1002/cpt.754 [epub ahead of print]
- Rodan AR and Jenny A. (2017) WNK kinases in development and disease. In: Andreas Jenny, editor, Protein Kinases in Development and Disease, Curr Topics Dev Biol, Burlington: Academic Press, 123: 1-47
- Mahajan A, Rodan AR, Le TH, Gaulton KJ, Haessler J, Stilp AM, Kamatani Y, Zhu G, Sofer T, Puri S, Schellinger JN, Chu PL, Cechova S, van Zuydam N; SUMMIT Consortium; BioBank Japan Project, Arnlov J, Flessner MF, Giedraitis V, Heath AC, Kubo M, Larsson A, Lindgren CM, Madden PA, Montgomery GW, Papanicolaou GJ, Reiner AP, Sundström J, Thornton TA, Lind L, Ingelsson E, Cai J, Martin NG, Kooperberg C, Matsuda K, Whitfield JB, Okada Y, Laurie CC, Morris AP, Franceschini N. (2016) Trans-ethnic fine mapping highlights kidney-function genes linked to salt sensitivity. Am J Hum Genet 99: 636-646
- Wu Y, Baum M, Huang C-L, Rodan AR. (2015) Two inwardly-rectifying potassium channels, Irk1 and Irk2, play redundant roles in Drosophila renal tubule function. Am J Physiol Regul Integr Comp Physiol 309: R747-56
- Schellinger JN and Rodan AR. (2015) Use of the Ramsay assay to measure fluid secretion and ion flux rates in the Drosophila melanogaster Malpighian tubule. J Vis Exp 105: e53144
- Wu Y, Schellinger JN, Huang CL, Rodan AR. (2014) Hypotonicity stimulates potassium flux through the WNK-SPAK/OSR1 kinase cascade and the Ncc69 sodium-potassium-2-chloride cotransporter in the Drosophila renal tubule. J Biol Chem 289: 26131-42
- Rodan AR, Baum M, and Huang CL. (2012) The Drosophila NKCC Ncc69 is required for normal renal tubule function. Am J Physiol Cell Physiol 303: C883-C894.