Professor, Department of Biomedical Sciences
Department of Biomedical Sciences
James H Quillen College of Medicine
PO Box 70582
Stanton-Gerber Hall, Room B213
Phone: 423 439-2010
1. Ocular tissue size control
2. Taste bud regeneration
3. Stem cell self-renewal and fate
Our research is focused on the retinal pigment epithelium (RPE), a tissue layer that is essential for coordinated maturation of neurons and glial cells in developing retinas, as well as for metabolic support of photoreceptor cells, the rods and cones, in mature retinas. Unlike most mammalian tissues, the RPE achieves its adult proportions through an increase in both cell number and cell size. Overall growth occurs in two partially overlapping phases, with cell division occurring primarily during the embryonic period and cell enlargement during postnatal development. We are specifically interested in genes that regulate the balance between cell proliferation and cell mass, and how these interact with the cell differentiation program. To examine these questions we are using a variety of approaches to study mice that have been genetically engineered to contain mutations in specific genes that control the cell division cycle. Our results have shown that in animals lacking the p27(Kip1) gene, an important cell cycle inhibitory protein, the RPE undergoes additional nuclear and cellular divisions. However, while the mutant epithelium contains approximately twice as many cells as wild-type controls, each cell in the monolayer is, on average, one-half normal size. This results in a tissue that displays few changes in its overall structure. On the other hand, retinas from these same p27(Kip1) “knock-out” animals exhibit large areas of detachment in which the physical interaction of the RPE with photoreceptor cells is severely disrupted. These studies have potential relevance for human diseases such as proliferative retinopathy and macular degeneration, in which there is an abnormal increase or decrease, respectively, in the number of RPE cells.
Accelerated turnover of taste bud cells in mice deficient for the cyclin-dependent kinase inhibitor p27Kip1.
Harrison TA, Smith Adams LB, Moore PD, Perna MK, Sword JD, Defoe DM. BMC Neurosci. 2011 Apr 20;12:34
Defects in retinal pigment epithelium cell proliferation and retinal attachment in mutant mice with p27(Kip1) gene ablation.
Defoe DM, Adams LB, Sun J, Wisecarver SN, Levine EM. Mol Vis. 2007 Feb 27;13:273-86