The central objective of the research in our laboratory is to understand the tissue-specific regulation of gene transcription in  brain and liver cells. We are studying the transcriptional regulation of a cluster of human genes encoding members of the serine proteinase inhibitor (serpin) family that has been mapped to a 280 kbp region of chromosome 14q32.1.  The serpin genes are organized into two subclusters that are most likely regulated by independent mechanisms.  The distal subcluster contains genes coding for kallistatin (KAL), protein C inhibitor (PCI) and alpha-1-antichymotrypsin (ACT).  All of these genes are highly transcribed in hepatocytes and hepatoma cells but only the ACT gene is expressed in astrocytes.
    In addition, ACT is a strong positive acute phase reactant activated by several proinflammatory cytokines both in the brain and liver.  Drastically increased levels of ACT have been found in the brains of Alzheimer's patients with the ACT protein co-localized with filamentous deposits containing polymers of beta-amyloid peptide.  Recently, ACT has also been shown to enhance formation of beta-amyloid deposits in a double transgenic mouse model of Alzheimer's disease.
    In human astrocytes, expression of ACT is regulated by inflammatory cytokines including IL-1, TNF, oncostatin M (OSM) and complexes of IL-6/soluble IL-6 receptor.  We have already identified an IL-1/TNF-resonsive enhancer and a proximal OSM/IL-6-responsive element upstream of the coding region of the ACT gene.  Furthermore, our recent results suggest that astrocyte and hepatocyte specific chromatin structures of the distal serpin subcluster determine the expression of serpin genes in astrocytes and hepatocytes.  Currently, we are using several molecular and cell biology approaches to identify the astrocyte-specific factors that determine the chromatin structure of the distal serpin subcluster .  Identifying the mechanism(s) responsible for the astrocyte-specific transcriptional regulation of the ACT gene is critical for a full understanding of the astrocyte-specific expression of ACT and its role in the etiology of Alzheimer's disease.

Goldstein, J.M., Nelson, D., Kordula, T. Mayo, J.A. and Travis, J. Extracellular Arginine Aminopeptidase from Streptococcus gordonii FSS2. Infection and Immunity, 70, 836-843, 2002.

Kordula, T., Banbula, A., Macomson, J. and Travis, J. Isolation and properties of Stachyrase A; a chymotrypsin-like serine proteinase from Stachybotrys chartarum. Infection and Immunity, 70, 419-421, 2002.

Kasza, A., Kowanetz, M., Poslednik, K., Witek, B., Kordula T. and Koj, A. Epidermal Growth Factor and proinflammatory cytokine regulate expression of plasminogen activation system in U373-MG astrocytoma cells. Cytokine, 16, 187-190, 2001.

Goldstein, J.M., Banbula, A., Kordula, T., Mayo, J.A. and Travis, J. A Novel Extracellular x-Prolyl Dipeptidyl-Peptidase fromStreptococcus gordonii FSS2: An Emerging Subfamily of Viridans Streptococcal x-Pro DPPs.Infection and Immunity, 69, 5494-501, 2001.

Kasza, A., Rogowski, K., Kilarski, W., Sobota, R., Bernas, T., Dobrucki, J., Travis, J., Koj, A., Bugno, M. and Kordula, T. Differential effects of Oncostatin M and Leukemia Inhibitory Factor expression in astrocytoma cells. Biochem. J., 355, 307-314, 2001.

Kordula, T., Bugno, M., Rydel, R.E., and Travis, J. Mechanism of interleukin-1 and tumor necrosis factor a-dependent regulation of alpha-1-antichymotrypsin gene in human astrocytes. J. Neurosciences, 20, 7510-7516, 2000.

Sobota, R., Szwed, M., Kasza, A., Bugno, M. and Kordula, T. Parthenolide Inhibits activation of Signal Transducers and Activators of Transcription (STATs) induced by cytokines of the IL-6 family. Biochem. Biophys. Res. Commun., 267, 329-333. 2000.

T. Kordula's list of publications

National Institute of Health (NIH)
National Institute of Biotechnology Information (NCBI)
ExPASy Molecular Biology Server
BLAST Searches from NCBI
PubMed search engine from NCBI
Medline from BioMedNet
Ohio Link
Science Citation Index Expanded (ISI)
Pedro's BioMolecular Research Tools
Grantsnet - funding sources

Pedro's listing of online journals

Annual Review of Biochemistry
Annual Review of Genetics
Annual Review of Immunology
Biochemical Journal
Cell
EMBO Journal
Genes and Development
Glia
Immunity
Journal of Biological Chemistry
Journal of Immunology
Journal of Neuroscience
Molecular and Cellular Biology
Molecular Cell
Nature
Neuron
Nucleic Acids Research
Proceedings of National Academy of Sciences, USA
Science

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