Associate Professor of Internal Medicine and Adjunct Associate Professor of Human Genetics
Ion Transport, Kinase, Drosophila, Kidney, Osmoregulation, Blood Pressure, Salt Sensitivity, Potassium, Sodium, Metabolism
The kidney plays a central role in maintaining homeostasis of ions and water in the body. However, the diet of early humans (low sodium, high potassium) is the opposite of the modern diet (high sodium, low potassium). My laboratory is interested in how the kidney responds to the high sodium, low potassium diet in ways that are both adaptive and maladaptive.
Underlying the kidneys’ ability to regulate salt and water is the process of ion transport, the vectorial movement of ions across cell membranes. My laboratory uses the fruit fly Drosophila melanogaster as a model organism to study ion transport processes relevant to human physiology. Drosophila have a short life cycle, sophisticated genetics, and in many cases single gene representation of mammalian multi-gene families, simplifying analysis of pathways of interest. One project in the lab is focused on WNK kinases, which are mutated in a human disorder characterized by high blood pressure and high potassium. We are studying how these kinases are directly regulated by ions and in turn regulate ion transporters and channels. A second project deals with how flies respond to high salt diet, with a focus on genes that increase or decrease the ability to cope with high salt, and interactions between metabolism and salt sensitivity. In a third project, we are investigating membrane trafficking pathways that we identified in a forward genetic screen for genes that interact with WNK. Our goal is to understand the regulatory and ion transport mechanisms underlying the response to varying diets and to translate these insights into improved understanding of ion transport processes in health and disease.
- Rodan AR (2022) Regulation of distal nephron transport by intracellular chloride and potassium. Nephron, 147: 203-211. doi: 10.1159/000526051
- Goldsmith EJ and Rodan AR (2023) Intracellular ion control of WNK signaling. Annual Review of Physiology, 85: 383-406. doi: 10.1146/annurev-physiol-031522-080651
- Boyd-Shiwarski CR, Shiwarski DJ, Griffiths SE, Beacham RT, Norrell L, Morrison DE, Wang J, Mann J, Tennant W, Anderson EN, Franks J, Calderon M, Connolly KA, Cheema MU, Weaver CJ, Nkashama LJ, Weckerly CC, Querry KE, Bhan Pandey U, Donnelly CJ, Sun D, Rodan AR, Subramanya AR. (2022) WNK kinases sense molecular crowding and rescue cell volume via phase separation. Cell, 185: 4488-4506. doi: 10.1016/j.cell.2022.09.042.
- Jonusaite S and Rodan AR (2021). Molecular basis for epithelial morphogenesis and ion transport in the Malpighian tubule. Curr Opin Insect Sci, 47: 7-11.
- Hyndman KA, Isaeva E, Palygin O, Mendoza LD, Rodan AR, Staruschenko A, Pollock JS (2021). Role of collecting duct principal cell NOS1b in sodium and potassium homeostasis. Physiol Rep, 9: e15080. Doi: 10.14814/phy2.15080
- Schellinger JN, Sun Q, Pleinis JM, An SW, Hu J, Mercenne G, Titos I, Huang CL, Rothenfluh A, Rodan AR (2022). Chloride oscillation in pacemaker neurons regulates circadian rhythms through a chloride-sensing WNK kinase signaling cascade. Current Biology, 32: 1-10. doi: 10.1016/j.cub.2022.03.017
- Balderas E, Eberhardt DR, Lee S, Pleinis JM, Sommakia S, Balynas AM, Yin X, Parker MC, Maguire CT, Cho S, Szulik M, Bakhtina A, Bia RD, Friederich MW, Locke TM, Van Hove JLK, Drakos SG, Sancak Y, Tristani-Firouzi M, Franklin S, Rodan AR, Chaudhuri D (2022). Mitochondrial calcium uniporter stabilization preserves energetic homeostasis during Complex I impairment. Nat Commun, 13: 2769. doi: 10.1038/s41467-022-30236-4
- 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.