Transporters-mediated metabolic communication lab
New metabolic pathways governing bioenergetics in the immune system, renal epithelia and liver.
We study the molecular basis of novel metabolic communication pathways that regulate bioenergetics in multiple tissues. When impaired, these processes hamper immune responses, cellular metabolism and may lead to metabolic and inflammatory diseases. These include inflammatory bowel diseases, kidney diseases and cancer.
About
Our major interest is in the mechanism and function of transmembrane proteins mediating the transport of electrolytes and metabolic products as it relates to disease states. Our research focuses on slc26 and slc13 transporters since very little was known about members of this family, however, a rapidly growing number of diseases that are linked to disruption of genes encoding Slc26 and slc13 transporters underscores their physiological importance. Using bioinformatics tools and various experimental techniques we have established a novel structure-function and protein-protein interaction models of these transporters utilizing computer modeling and experimental results in vitro and in vivo. Our study of biophysical, biochemical and functional properties of transporter function had a major impact on our understanding of Cl-, pH and carboxylic acid homeostasis mechanisms and metabolism in physiological and pathophysiological conditions.
Funding
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Selected Publications
1. Verma, A., Pittala, S., Alhozeel, B., Shteinfer-Kuzmine, A., Ohana, E., Gupta, R., Chung, J. H., and Shoshan-Barmatz, V. (2022) The role of the mitochondrial protein VDAC1 in inflammatory bowel disease: a potential therapeutic target. Molecular therapy : the journal of the American Society of Gene Therapy 30, 726-744
2. Rosenberg, G., Yehezkel, D., Hoffman, D., Mattioli, C. C., Fremder, M., Ben-Arosh, H., Vainman, L., Nissani, N., Hen-Avivi, S., Brenner, S., Itkin, M., Malitsky, S., Ohana, E., Ben-Moshe, N. B., and Avraham, R. (2021) Host succinate is an activation signal for Salmonella virulence during intracellular infection. Science 371, 400-405
3. Fremder, M., Kim, S. W., Khamaysi, A., Shimshilashvili, L., Eini-Rider, H., Park, I. S., Hadad, U., Cheon, J. H., and Ohana, E. (2021) A transepithelial pathway delivers succinate to macrophages, thus perpetuating their pro-inflammatory metabolic state. Cell reports 36, 109521
4. Shimshilashvili, L., Aharon, S., Moe, O. W., and Ohana, E. (2020) Novel Human Polymorphisms Define a Key Role for the SLC26A6-STAS Domain in Protection From Ca(2+)-Oxalate Lithogenesis. Frontiers in pharmacology 11, 405
5. Luscher, B. P., Vachel, L., Ohana, E., and Muallem, S. (2020) Cl(-) as a bona fide signaling ion. American journal of physiology. Cell physiology 318, C125-C136
6. Khamaysi, A., Aharon, S., Eini-Rider, H., and Ohana, E. (2020) A dynamic anchor domain in slc13 transporters controls metabolite transport. The Journal of biological chemistry 295, 8155-8163
7. Khamaysi, A., Anbtawee-Jomaa, S., Fremder, M., Eini-Rider, H., Shimshilashvili, L., Aharon, S., Aizenshtein, E., Shlomi, T., Noguchi, A., Springer, D., Moe, O. W., Shcheynikov, N., Muallem, S., and Ohana, E. (2019) Systemic Succinate Homeostasis and Local Succinate Signaling Affect Blood Pressure and Modify Risks for Calcium Oxalate Lithogenesis. Journal of the American Society of Nephrology : JASN
8. Vachel, L., Shcheynikov, N., Yamazaki, O., Fremder, M., Ohana, E., Son, A., Shin, D. M., Yamazaki-Nakazawa, A., Yang, C. R., Knepper, M. A., and Muallem, S. (2018) Modulation of Cl(-) signaling and ion transport by recruitment of kinases and phosphatases mediated by the regulatory protein IRBIT. Science signaling 11
9. Wedenoja, S., Khamaysi, A., Shimshilashvili, L., Anbtawe-Jomaa, S., Elomaa, O., Toppari, J., Hoglund, P., Aittomaki, K., Holmberg, C., Hovatta, O., Tapanainen, J. S., Ohana, E., and Kere, J. (2017) A missense mutation in SLC26A3 is associated with human male subfertility and impaired activation of CFTR. Scientific reports 7, 14208
10. Roy, S., Dey, K., Hershfinkel, M., Ohana, E., and Sekler, I. (2017) Identification of residues that control Li(+) versus Na(+) dependent Ca(2+) exchange at the transport site of the mitochondrial NCLX. Biochimica et biophysica acta. Molecular cell research 1864, 997-1008
11. Shcheynikov, N., Son, A., Hong, J. H., Yamazaki, O., Ohana, E., Kurtz, I., Shin, D. M., and Muallem, S. (2015) Intracellular Cl- as a signaling ion that potently regulates Na+/HCO3- transporters. Proceedings of the National Academy of Sciences of the United States of America 112, E329-337
12. Ohana, E. (2015) Transepithelial ion transport across duct cells of the salivary gland. Oral diseases 21, 826-835
13. Park, M., Ohana, E., Choi, S. Y., Lee, M. S., Park, J. H., and Muallem, S. (2014) Multiple roles of the SO4(2-)/Cl-/OH- exchanger protein Slc26a2 in chondrocyte functions. The Journal of biological chemistry 289, 1993-2001
14. Ohana, E., Shcheynikov, N., Moe, O. W., and Muallem, S. (2013) SLC26A6 and NaDC-1 transporters interact to regulate oxalate and citrate homeostasis. Journal of the American Society of Nephrology : JASN 24, 1617-1626
15. Hong, J. H., Yang, D., Shcheynikov, N., Ohana, E., Shin, D. M., and Muallem, S. (2013) Convergence of IRBIT, phosphatidylinositol (4,5) bisphosphate, and WNK/SPAK kinases in regulation of the Na+-HCO3- cotransporters family. Proceedings of the National Academy of Sciences of the United States of America 110, 4105-4110
16. Park, S., Hong, J. H., Ohana, E., and Muallem, S. (2012) The WNK/SPAK and IRBIT/PP1 pathways in epithelial fluid and electrolyte transport. Physiology 27, 291-299
17. Ohana, E., Shcheynikov, N., Park, M., and Muallem, S. (2012) Solute carrier family 26 member a2 (Slc26a2) protein functions as an electroneutral SOFormula/OH-/Cl- exchanger regulated by extracellular Cl. The Journal of biological chemistry 287, 5122-5132
18. Lee, M. G., Ohana, E., Park, H. W., Yang, D., and Muallem, S. (2012) Molecular mechanism of pancreatic and salivary gland fluid and HCO3 secretion. Physiological reviews 92, 39-74
19. Ohana, E., Shcheynikov, N., Yang, D., So, I., and Muallem, S. (2011) Determinants of coupled transport and uncoupled current by the electrogenic SLC26 transporters. The Journal of general physiology 137, 239-251
20. Yang, D., Shcheynikov, N., Zeng, W., Ohana, E., So, I., Ando, H., Mizutani, A., Mikoshiba, K., and Muallem, S. (2009) IRBIT coordinates epithelial fluid and HCO3- secretion by stimulating the transporters pNBC1 and CFTR in the murine pancreatic duct. The Journal of clinical investigation 119, 193-202
21. Ohana, E., Yang, D., Shcheynikov, N., and Muallem, S. (2009) Diverse transport modes by the solute carrier 26 family of anion transporters. The Journal of physiology 587, 2179-2185
22. Ohana, E., Hoch, E., Keasar, C., Kambe, T., Yifrach, O., Hershfinkel, M., and Sekler, I. (2009) Identification of the Zn2+ binding site and mode of operation of a mammalian Zn2+ transporter. The Journal of biological chemistry 284, 17677-17686
23. Ohana, E., Sekler, I., Kaisman, T., Kahn, N., Cove, J., Silverman, W. F., Amsterdam, A., and Hershfinkel, M. (2006) Silencing of ZnT-1 expression enhances heavy metal influx and toxicity. Journal of molecular medicine 84, 753-763
24. Segal, D., Ohana, E., Besser, L., Hershfinkel, M., Moran, A., and Sekler, I. (2004) A role for ZnT-1 in regulating cellular cation influx. Biochemical and biophysical research communications 323, 1145-1150
25. Palty, R., Ohana, E., Hershfinkel, M., Volokita, M., Elgazar, V., Beharier, O., Silverman, W. F., Argaman, M., and Sekler, I. (2004) Lithium-calcium exchange is mediated by a distinct potassium-independent sodium-calcium exchanger. The Journal of biological chemistry 279, 25234-25240
26. Ohana, E., Segal, D., Palty, R., Ton-That, D., Moran, A., Sensi, S. L., Weiss, J. H., Hershfinkel, M., and Sekler, I. (2004) A sodium zinc exchange mechanism is mediating extrusion of zinc in mammalian cells. The Journal of biological chemistry 279, 4278-4284
Contact info
The department of clinical biochemistry and pharmacology,
Faculty of Health sciences, Ben-Gurion university,
Soroka Medical Center, bldg. 12, 4th floor
Be'er Sheva, Israel
+972-53-3351695
