Epigenetic programming of kidney development

B05

Project Summary

The number of nephrons is a major determinant for the development of chronic kidney disease and hypertension. We hypothesise a link between environmental factors, epigenetic modification and nephron formation. To identify the complex gene regulatory networks of nephron programming influenced by DNA methylation, transcriptome analysis will be combined with DNA methylation analysis on DNA methyltransferase-deficient renal cell populations. In addition, known maternal environmental determinants of nephron formation will be tested for their influence on DNA methylation.

Selected project-relevant publications

  • Huber T.B. and Holthofer H. (2017) From genetics to personalized nephrology: kidney research at a tipping point. Cell Tissue Res 369, 1-4.
  • Assady S., Wanner N., Skorecki K.L. and Huber T.B. (2017) New Insights into Podocyte Biology in Glomerular Health and Disease. J Am Soc Nephrol 28, 1707-1715.
  • Fantus D., Rogers N.M., Grahammer F., Huber T.B. and Thomson A.W. (2016) Roles of mTOR complexes in the kidney: implications for renal disease and transplantation. Nat Rev Nephrol 12, 587-609.
  • Sheikh B.N., Bechtel-Walz W., Lucci J., Karpiuk O., Hild I., Hartleben B., Vornweg J., Helmstadter M., Sahyoun A.H., Bhardwaj V., Stehle T., Diehl S., Kretz O., Voss A.K., Thomas T., Manke T., Huber T.B. and Akhtar A. (2015) MOF maintains transcriptional programs regulating cellular stress response. Oncogene 35, 2698-2710
  • Godel M., Grahammer F. and Huber T.B. (2015) Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med 372, 1073.
  • Chung J.J., Huber T.B., Godel M., Jarad G., Hartleben B., Kwoh C., Keil A., Karpitskiy A., Hu J., Huh C.J., Cella M., Gross R.W., Miner J.H. and Shaw A.S. (2015) Albumin-associated free fatty acids induce macropinocytosis in podocytes. J Clin Invest 125, 2307-2316.
  • Grahammer F., Haenisch N., Steinhardt F., Sander L., Roerden M., Arnold F., Cordts T., Wanner N., Reichardt W., Kerjaschki D., Ruegg M.A., Hall M.N., Moulin P., Busch H., Boerries M., Walz G., Artunc F. and Huber T.B. (2014) mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress. Proc Natl Acad Sci U S A 111, E2817-2826.
  • Canaud G., Bienaime F., Viau A., Treins C., Baron W., Nguyen C., Burtin M., Berissi S., Giannakakis K., Muda A.O., Zschiedrich S., Huber T.B., Friedlander G., Legendre C., Pontoglio M., Pende M. and Terzi F. (2013) AKT2 is essential to maintain podocyte viability and function during chronic kidney disease. Nat Med 19, 1288-1296.
  • Bechtel W., Helmstadter M., Balica J., Hartleben B., Schell C. and Huber T.B. (2013) The class III phosphatidylinositol 3-kinase PIK3C3/VPS34 regulates endocytosis and autophagosome-autolysosome formation in podocytes. Autophagy 9, 1097-1099.