The GI Stem Cell Research Lab has multiple projects within three major research themes geared toward finding novel treatments for aging and aging-related diseases and disorders.
These three research themes are:
- Understanding epigenetic regulation of gastric pacemaker stem cell aging
- Designing methods for regenerating aged gastric stem cells
- Developing novel therapeutics targeting wingless-type mouse mammary tumor virus (MMTV) integration site (Wnt) signaling in aging and cancer
Dr. Hayashi and his research team are investigating several ongoing projects.
Epigenetic regulation of gastric pacemaker stem cell aging
Age-related gastric dysfunction is associated with anorexia underlying sarcopenia and frailty, but the mechanisms of this dysfunction are incompletely understood. Interstitial cells of Cajal (ICC), the pacemaker and neuromodulator cells of the gastrointestinal (GI) tract, decline with age, as do ICC stem cells (ICC-SC). Research in Dr. Hayashi's lab seeks to unravel the molecular and epigenetic mechanisms of ICC-SC decline underlying aging-associated ICC depletion.
By identifying the factors responsible for mediating these mechanisms, the Hayashi lab hopes to develop novel therapeutic targets to counteract ICC-SC and ICC decline with age.
Regeneration of aged stem cells
Aging-associated depletion of ICC-SC is due to reduced extracellular signal-regulated kinase (ERK) signaling arising from the decline of insulin-like growth factor-1 (IGF-1) during aging. A project of Dr. Hayashi's research team is to examine whether ERK stimulation by IGF-1 can mitigate aging-related ICC and ICC-SC decline. His lab is also planning to evaluate the therapeutic efficacy of ICC-SC transplantation in age-related ICC-SC and ICC loss and gastric motor dysfunction.
These projects aim to identify a novel pharmacological and stem cell-based therapeutic approaches to restore gastric motor functions that decline with age. This research also explores the novel concept that improving gastric motor function is an important therapeutic strategy to combat aging-associated disorders and diseases, improve quality of life, and increase longevity.
Novel therapeutics targeting Wnt signaling for stem cell aging and cancer
The Wnt (wingless-type MMTV integration site family) pathway regulates normal stem cell self-renewal in several tissues. But overactive or uncontrolled Wnt signaling can induce cellular senescence, a state of permanent cell cycle arrest, or lead to cancer. Previously, Dr. Hayashi demonstrated that increased Wnt signaling induced ICC-SC cell cycle arrest leading to ICC loss with age.
The goal of this project is to determine why Wnt signaling can induce the cell cycle arrest stage (aging) or the overactive cell cycle stage (cancer).
Findings from this research may ultimately lead to new ways to modulate aged or cancer cells, thus reversing diseases and disabilities associated with aging and cancer.