Our Science – Flomerfelt Website

Francis A. Flomerfelt, Ph.D.

Experimental Transplantation and Immunology Branch Transplantation Immunology Section Staff Scientist Center for Cancer Research National Cancer Institute Building 10 - Magnuson CC, Room 6N102 Bethesda, MD 20892-1203 Phone:   301-402-4316 Fax:   301-451-8299 E-Mail:   flomerff@mail.nih.gov

Biography

Flomerfelt FA, El Kassar N, Gurunathan C, Chua KS, League SC, Schmitz S, Gershon TR, Kapoor V, Yan XY, Schwartz RH, Gress RE. (2010) Tbata modulates thymic stromal cell proliferation and thymus function. J Exp Med. 2010 Oct 25;207(11):2521-32. Epub 2010 Oct 11.

Flomerfelt, F.A., Kim M.G., and Schwartz, R.H. (2000). Spatial, a gene expressed in thymic stromal cells, depends on 3-dimensional thymus organization for its expression. Genes and Immunity, 1(6):391-401

Chen, C., Kim, M.G., Lyu, M.S., Kozak, C., Schwartz, R.H., and Flomerfelt,F.A. (2000). Characterization of the mouse gene, human promoter, and human cDNA of TSCOT reveals strong interspecies homology. Biochim Biophys Acta. 493(1-2):159-69.

Flomerfelt, F.A., Briehl, M.M., Dowd, D.A., Dieken, E.S. and Miesfeld, R.L. (1993). Elevated glutathione S-transferase gene expression is an early event during steroid-induced lymphocyte apoptosis, J. Cell Physiol. 154: 573-581.

Flomerfelt, F.A. and Miesfeld, R.L. (1994) Recessive mutations in a common pathway block thymocyte apoptosis induced by multiple signals, J. Cell Biology 127:1729-1742.

Research

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 recently cloned genes specifically expressed in thymic stromal cells. One of these, the SPATIAL gene product, is specifically expressed in thymic stromal cells. We have developed a mouse knockout model and are focused on determining the function of SPATIAL. Our goals include using this information to develop treatments to manipulate thymic stromal cells to improve thymus function in patients.

This page was last updated on 2/26/2013.