Skip to main content

Epigenetics and development

Marco Pontoglio
Team description

Our research centers on understanding the mechanisms governing gene expression and morphogenesis. Specifically, we investigate the roles of two transcription factors, HNF1alpha and HNF1beta, encoded by the HNF1A and HNF1B genes. Mutations in these genes are associated with diabetes and renal developmental disorders.

Cell growth, differentiation, and morphogenesis are critical events, and their disruption can result in severe developmental pathologies. These intricate processes are predominantly regulated by complex transcriptional networks in which transcription factors play a pivotal role. Analyzing the functions of transcription factors and understanding the mechanisms underlying their actions provide a unique perspective for comprehending intricate biological processes and pathophysiology. In recent years, as a paradigm for our research, we have focused on investigating the roles of HNF1alpha and HNF1beta, a small family of transcription factors known for their association with severe human diseases.

Our research objectives can be summarized in the following areas:

  • Genetic Programs - Explore the genetic programs controlled by HNF1A and HNF1B, particularly in epithelial morphogenesis and differentiation, with a focus on kidney development.
  • Epigenetic Inheritance - Investigate the unique epigenetic "bookmarking" properties of HNF1A and HNF1B.
  • Phenotypic Variability - Identify the mechanisms underlying the diverse phenotypes associated with HNF1A and HNF1B deficiencies, including the involvement of modifier genes.
  • Pharmacological Intervention - Evaluate the potential therapeutic benefits of specific compounds to restore HNF1B activity.

In pursuing these objectives, our research aims to shed light on the fundamental biological processes controlled by HNF1A and HNF1B, ultimately contributing to a better understanding of the complex mechanisms underlying severe human diseases and potential therapeutic interventions

Key publications
Isnard P, Vergnaud P, Garbay S, Jamme M, Eloudzeri M, Karras A, Anglicheau D, Galantine V, Jalal Eddine A, Gosset C, Pourcine F, Zarhrate M, Gibier JB, Rensen E, Pietropaoli S, Barba-Spaeth G, Duong-Van-Huyen JP, Molina TJ, Mueller F, Zimmer C, Pontoglio M, Terzi F, Rabant M. A specific molecular signature in SARS-CoV-2-infected kidney biopsies. JCI Insight. 2023; Mar 8;8(5):e165192. doi: 10.1172/jci.insight.165192. PMID: 36749641 ; PMCID: PMC10077488.
Miao Z, Balzer MS, Ma Z, Liu H, Wu J, Shrestha R, Aranyi T, Kwan A, Kondo A, Pontoglio M, Kim J, Li M, Kaestner KH, Susztak K. Single cell regulatory landscape of the mouse kidney highlights cellular differentiation programs and disease targets. Nat Commun. 2021; Apr 15;12(1):2277. doi: 10.1038/s41467-021-22266-1. PMID: 33859189 ; PMCID: PMC8050063.
Blanc T, Goudin N, Zaidan M, Traore MG, Bienaime F, Turinsky L, Garbay S, Nguyen C, Burtin M, Friedlander G, Terzi F, Pontoglio M. Three-dimensional architecture of nephrons in the normal and cystic kidney. Kidney Int. 2021; Mar;99(3):632-645. doi: 10.1016/j.kint.2020.09.032. PMID: 33137337 .
Fiorentino A, Christophorou A, Massa F, Garbay S, Chiral M, Ramsing M, Rasmussen M, Gubler MC, Bessieres B, Heidet L, Fischer E, Pontoglio M. Developmental Renal Glomerular Defects at the Origin of Glomerulocystic Disease. Cell Rep. 2020; Oct 27;33(4):108304. doi: 10.1016/j.celrep.2020.108304. PMID: 33113370 .
Phelep A, Laouari D, Bharti K, Burtin M, Tammaccaro S, Garbay S, Nguyen C, Vasseur F, Blanc T, Berissi S, Langa-Vives F, Fischer E, Druilhe A, Arnheiter H, Friedlander G, Pontoglio M, Terzi F. MITF - A controls branching morphogenesis and nephron endowment. PLoS Genet. 2017; Dec 14;13(12):e1007093. doi: 10.1371/journal.pgen.1007093. PMID: 29240767 ; PMCID: PMC5746285.
Funding and grants