Tomek Kordula, Ph.D.Associate Professor of Biochemistry & Molecular Biology
PO Box 980614
Richmond, VA 23298-0614
- M.S., 1988, Jagiellonian University, Poland
- Ph.D., 1992, Jagiellonian University, Poland
Department of Biochemistry & Molecular Biology, University of Georgia, 1993-1996
The overall research interest of the laboratory is focused on the molecular mechanisms regulating both tissue-specific and cytokine-induced gene transcription. The Serpin gene cluster located on chromosome 14 contains at least 12 serpin genes that are specifically expressed in different tissues. The distal part of this cluster is occupied by three genes that are all expressed in hepatocytes; however, only one gene encoding an amyloid-associated protein a1-antichymotrypsin (ACT) is expressed in astrocytes. ACT associates with b-amyloid peptide, and its overexpression enhances formation of b amyloid plaques in a double transgenic model of Alzheimer’s disease. We are studying molecular mechanisms that govern basal astrocyte-specific expression of the ACT gene, and its stimulation by proinflammatory cytokines. We have shown that the tissue-specific chromatin structure determines expression of the ACT gene in astrocytes. This structure is determined by yet to be identified astrocyte-specific transcription factor. In addition, we have characterized molecular mechanisms that control ACT expression in astrocytes exposed to several cytokines including IL-1, TNF, IL-6 and oncostatin M.
Genes encoding components of the plasminogen activator system are tightly regulated in astrocytes by several cytokines and growth factors. This transcriptional regulation is one of the molecular mechanisms precisely controlling proteolytic balance at the site of brain injury, allowing migration and repopulation of injury sites. We are studying both the signaling pathways and transcription factors that regulate transcription of genes encoding components of the plasminogen activator system in astrocytes in response to cytokines and growth factors.
In order to accomplish our goals we use tissue culture systems and in vitro approaches.