As we grow older our organs do not function as efficiently and following injury or disease are less able to repair themselves, leading to many health problems we associate with ageing. Nerves surround organs in our bodies and interact with progenitor cells, the initiators of development within each organ, and without nerve input progenitor cells diminish. My group investigates how the progenitor cells and nerves interact in ageing organs. I predict that if communication between nerves and progenitor cells is improved the ageing organ will work better and be more able to repair/regenerate itself and this would greatly improve patient quality of life.
Human tissues regenerate during embryogenesis, yet lose this ability in adulthood, particularly with advanced age, a process that remains incompletely understood. With age the functionality of tissues and the ability to repair/regenerate following injury and disease is substantially reduced, leading to many of the hallmark diseases of aging. The mechanistic role of progenitor cells particularly interests me, particularly the reactivation/manipulation of resident progenitor cells to maintain tissue homeostasis and repair during ageing. Using the acini-ductal network of the developing and adult human and murine salivary gland as models of epithelial organogenesis and homeostasis, I have previously demonstrated that parasympathetic nerves preferentially establish, maintain and replenish functional saliva-producing acinar cells via regulation of the transcription factor SOX2. My group investigates how age influences the nerve to progenitor cell communication necessary for adult organ homeostasis and regeneration, and how the SOX2+ progenitor cells themselves and their interactions with the niche change throughout development and adult ageing. Understanding the effect age plays on the progenitor cell to niche interaction will allow a more targeted approach to reinnervating ageing organs and as such improving organ function and regeneration.
The University of Edinburgh Chancellor’s Fellowship (2017-2022)
Saul Villeda, University of California San Francisco, USA http://profiles.ucsf.edu/saul.villeda
Michael Sherratt, The University of Manchester https://www.research.manchester.ac.uk/portal/michael.j.sherratt.html