HNF1B is a transcription factor involved in the epigenetic bookmarking whose mutations are known to be responsible for renal developmental defects and renal disease. The goal of this project is to elucidate the cellular and molecular mechanisms that accounts for the development of renal lesions after HNF1B inactivation in adult kidney. While much is known about the role of HNF1B in kidney development, with mutations in HNF1B being a primary cause of Congenital Abnormalities of the Kidney and Urinary Tract (CAKUT), little is known about its possible function in tissue homeostasis in the adult kidney. With the use of an inducible kidney specific inactivation, our results have shown that when HNF1B is inactivated in adult mouse kidneys there is a rapid and drastic tubular atrophy and interstitial fibrosis. This phenotype recapitulates the traits observed in many HNF1B adult patients. This research project will use transcriptomic analysis (bulk and single cell) and chromatin immunoprecipitation (ChIP-seq) approaches, to assess the identity of the genetic program of HNF1B in adult kidney to clarify the functions played by this transcription factor in adult kidneys. In parallel, the candidate will characterize the cellular events that lead to tubular atrophy and fibrosis.
- Improve our understanding of the molecular mechanisms that account for the function played by HNF1B in postnatal life;
- Identify the genetic networks responsible for the specific phenotype linked to HNF1B deficiency;