Our research tackles insulin resistance, with a particular focus on the effect of this disease on wound healing processes.
Our research tackles insulin resistance, a condition associated with obesity and type II diabetes in which our tissues gradually lose their capacity to respond to the hormone insulin. We are interested in how insulin resistance affects our body’s ability to repair itself when damaged. Within a given tissue, stromal-epithelial interactions are essential for maintaining a balance between scarring and epithelialization during injury. Our major goal is to understand how insulin regulates these local interactions to influence the wound healing process in health and disease.
We have recently shown that insulin can remotely control epithelial progenitor cells in the liver by promoting local paracrine signals from their stromal niche (Manzano-Núñez F, et al. PLoS Biol. 2019). In doing so, we were the first to demonstrate a role for insulin signals in the regulation of fibroblast growth factor 7 (FGF7), a driver of epithelial wound healing in organs such as skin. We are currently working to unravel the mechanism(s) underlying this novel signaling crosstalk by pursuing the following questions:
- How does the spatial patterning of insulin sensitivity in epithelial progenitor cells direct local sensitivity to paracrine FGFs?
- How does insulin resistance in stroma limit the survival of FGF7-producing cells to the advantage of those that produce scar tissue?
- How does insulin resistance affect stromal-epithelial interactions during the progression of human liver cancer?
Get to know us better
The people who make it all possible
Matilde D' Angelo
Mª José Arambul Anthony
Our scientific contributions
Insulin resistance disrupts epithelial repair and niche-progenitor Fgf signaling during chronic liver injury
F. MANZANO-NUNEZ, M. ARAMBUL-ANTHONY, A. ALBINANA, A. TASSIAS, C. UMANZOR, I. GASCO, A. HERRERA, J. VILA, D. BURKS and L. NOON
PLOS BIOLOGY, 2019 Jan,  DOI:  10.1371/journal.pbio.2006972,  Vol. 17,  pag. e2006972
Autophagy is a gatekeeper of hepatic differentiation and carcinogenesis by controlling the degradation of Yap
Lee YA, Noon LA, Akat KM, Ybanez MD, Lee TF, Berres ML, Fujiwara N, Goossens N, Chou HI, Parvin-Nejad FP, Khambu B, Kramer EGM, Gordon R, Pfleger C, Germain D, John GR, Campbell KN, Yue Z, Yin XM, Cuervo AM, Czaja MJ, Fiel MI, Hoshida Y and Friedman SL
Nature Communications, 2018 Nov,  DOI:  10.1038/s41467-018-07338-z,  Vol. 9,  pag. 4962-4962
Contributions of metabolic dysregulation and inflammation to nonalcoholic steatohepatitis, hepatic fibrosis, and cancer.
Lade A, Noon LA and Friedman SL
CURRENT OPINION IN ONCOLOGY, 2014 Jan,  DOI:  10.1097/CCO.0000000000000042,  Vol. 26,  pag. 100-107
A High-Throughput In Situ Method for Estimation of Hepatocyte Nuclear Ploidy in Mice
F. MANZANO-NUNEZ, R. PETERS, D. BURKS and L. NOON
Jove-Journal of Visualized Experiments, 2020 Apr,  DOI:  10.3791/60095,  Vol. ,  pag. e60095