Tudorita Tumbar, professor of molecular biology and genetics in the College of Arts and Sciences, has received three related grants for the next five years, totaling $7.7 million, from the National Institutes of Health (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
The work aims to understand how stem cells function to fuel normal tissue maintenance and to repair injuries in actively regenerative tissues, such as skin. Discoveries could contribute to treatments for burns and skin aging.
Using mouse genetics and genomics, the Tumbar Lab is investigating the molecular mechanisms employed by stem cells to perform their normal function. Perturbations in these stem cell related mechanisms are thought to lead to many devastating conditions, such as cancer, vascular disease and aging.
Tissue stem cells are rare and difficult to identify and study in the intact mammalian tissue, but using innovative mouse genetic approaches the Tumbar Lab has been able to make new discoveries with respect to several aspects of stem cell organization using mouse skin as a model.
Epidermis is a skin component that is most essential for animal’s survival by providing the body’s barrier function. The Tumbar lab uncovered a novel spatial organization of two populations of epidermal stem cells in spatial domains with distinct exposure to the environment outside our bodies. Tumbar believes the more embedded domains contain more active stem cells that are kept protected from exposure to UV irradiation and from other challenges.
“We are currently investigating the physiological significance of spatial epidermal domain organization and the specific genes and molecular pathways involved in setting up this domain organization during organismal development,” Tumbar said. “In future, targeting these pathways may help in better manipulation of stem cells for building organotypic skin cultures for burn victims or enhance tissue regeneration in aged skin.”
This project is funded by a $2.6 million grant “Defining the heterogeneity of cell lineages in the inter-follicular epidermis.”
The other two NIH projects examine the molecular mechanisms that control function in a second population of skin stem cells, located in the hair follicle.
“Aside from their obvious function of growing new hair shafts that span epidermis, the hair follicle stem cells which reside embedded deep into the dermis have important functions in the organization of other cell types in the skin,” Tumbar said.
One important project in the lab is on the molecular cross-talking of hair follicle stem cells with endothelial cells, which are components of the vasculature. This ongoing work is supported by the $2.3 million grant, “Investigating the coordinated endothelial-epithelial interactions in adult hair cycle of mouse skin.”
The third project, a collaboration with John Lis, the Barbara McClintock Professor of molecular biology and genetics in the College of Agriculture and Life Sciences, is supported by the $2.8 million grant, “Tissue biology studies of histone modification, nascent transcription, and post-transcription regulation.” The study examines how hair follicle stem cells organize their genomes and control gene expression during normal hair growth and in response to wounding.
“These cell-intrinsic mechanisms of tight controlling gene expression allow tissue stem cells to maintain a dormant yet plastic cell fate state, poised for rapid activation and differentiation to more specialized cell types needed for tissue function,” Tumbar said.