Francis A. Flomerfelt, Ph.D.
Cellular interaction between lymphoid cells and stromal cell-derived signals is required to support T cell development. Dr. Flomerfelt is interested in identifying the modulators of thymus function and T cell development. To investigate the role of thymic stromal cells, he has cloned genes specifically expressed in these cells. One of these, the TBATA gene product, is specifically expressed in thymic stromal cells. Dr. Flomerfelt helped develop a mouse model to determine the function of the TBATA gene product. The goal of these studies is to develop treatments that improve thymic function in patients.
1) modulators of thymus function, 2) thymic stromal cells, 3) T cell development
The thymus is the major site for the production of T cells in vertebrates. The cellular components of the thymus can be divided into two broad groups. Lymphoid cells are derived from bone marrow stem cells. This group of cells includes thymocytes, which are the major cellular component of the thymus. The other group, collectively known as stromal cells, develops mostly from epithelial cells derived from endoderm of the third pharyngeal pouch, ectoderm of the corresponding brachial clefts, and mesoderm from the pharyngeal arch. Cellular interaction between lymphoid cells and stromal cell-derived signals is required to support T cell development.
A major lab interest is in the identification of modulators of thymus function and T cell development. Because of the interdependence between lymphoid and stromal cells, both cell types are involved in the control of thymus function. However, until recently, it was not appreciated that stromal cells appear to play a major role in regulation of thymus function. One of the better-known examples is the role of stromal cells in age-related decline of thymus function. This was illustrated by showing that bone marrow transplants were equally successful when done in young mice using bone marrow cells from old or young mice. The reciprocal experiment, using old mice as the host, results in sub-optimal thymic-dependent T cell reconstitution regardless of the source of bone marrow. Although it is accepted that changes in properties of thymic stromal cell are a major component of age-related decline in thymic function, there is little information on the molecular details that underlie this and other types of controls mediated by thymic stromal cells. To begin studies to investigate the role of thymic stromal cells, we cloned genes specifically expressed in thymic stromal cells. One of these, the TBATA gene product, is specifically expressed in thymic stromal cells. We have developed a mouse knockout model and are focused on determining the function of TBATA. Our goals include using this information to develop treatments to manipulate thymic stromal cells to improve thymus function in patients.
- J. Immunol. Methods. 375: 84-92, 2012. [ Journal Article ]
Rapamycin generates anti-apoptotic human Th1/Tc1 cells via autophagy for induction of xenogeneic GVHD.Autophagy. 6: 2010. [ Journal Article ]
- J. Exp. Med.. 207: 2521-32, 2010. [ Journal Article ]
- Curr. Opin. Immunol.. 16: 151-6, 2004. [ Journal Article ]
- Int. Immunol.. 24: 661-71, 2012. [ Journal Article ]
Frank is a Staff Scientist in the Experimental Transplantation and Immunology Branch of the NCI. He attended Iowa State University as an undergraduate and went to the University of Arizona for graduate studies.