James Dunn, MD, PhD

Professor and Chief, Division of Pediatric Surgery, UCLA School of Medicine;
Professor in Bioengineering, UCLA School of Engineering.

A major interest of Dr. Dunn is to demonstrate that a specific putative stem cell can give rise to long-lived clones that have multi-lineage potential. His hypothesis is that refinement of methods to isolate and propagate gut stem/progenitors cells will facilitate the in vitro and in vivo development along the secretory lineage as defined by unique markers. His goals are to (A) refine the techniques and materials that will promote the growth of clusters or single cells in vitro and in vivo; (B) investigate the contribution of intestinal myofibroblasts to the intestinal stem cell niche; (C) modulate the ability of stem/progenitor cells to form fully mature enteroendocrine cells in both in vivo and in vitro models; and (D) identify and characterize other markers from uncommitted progenitors to mature enteroendocrine cells in mice. To address these goals Dr. Dunn is pursuing the following specific aims. Specific Aim 1: To develop methods that overcome the anchorage dependency of gut epithelial cells, and promotes the survival, growth and differentiation of these cells in both in vivo and in vitro settings. Specific Aim 2: To assess the role of pericryptal myofibroblast in modulating proliferation of stem cells and the maturation of enteroendocrine cells in a novel clonogenic cell culture system. Specific Aim 3: To modulate the maturation of enteroendocrine cells from isolated uncommitted and committed endocrine progenitors in an in vivo and in vitro model. Specific Aim 4: Develop and verify further a group of unique lineage-specific markers that define distinct stages in the progression from uncommitted progenitor cells to fully mature enteroendocrine cells.