Konrad Pazdrak, MD, PhD

Senior Scientist, Biomolecular Resources Facility Instructor, Department of Biochemistry and Molecular Biology

2.230 Basic Science Building
301 University Blvd.
Galveston, TX 77555-0645
Phone: 409-747-0916
Fax: 409-747-4753
Email: kopazdra@utmb.edu

Research Interests

None of the currently available treatments for asthma and allergic disease are curative, but merely treat or prevent symptoms. The increasing incidence of asthma and allergic diseases emphasizes emphasizes the need to identify new therapeutic targets for the treatment of allergic inflammation. Animal models of asthma validate links between eosinophils and allergic pulmonary pathologies, arguing for the development of eosinophil targetd therapies in chronic allergic diseases. In spite of widely appreciated consensus on the need for targeting eosinophils for therapeutic purposes and magnitude of knowledge on the mechanism of eosinophil activation, there is still critical gap in the knowledge, how eosinophils maintain their activated phenotype status in the lung tissue. My long-term goal is to elucidate regulatory mechanisms controlling expression of effector proteins in activated eosinophils as a prerequisite to the development of therapeutic targets that can be used to attenuate eosinophilic inflammation. My former and current research interests include delineation of signaling pathways downstream of GM-CSF/IL-5/IL-3 receptor critical for eosinophil survival and activation. Although much is known about signal initiation from GM-CSF receptor, the mechanisms underlying propagation and maintenance of activating signals are not fully understood. For example, diminished expression of the GM-CSF receptor and decreased responsiveness of cells to cytokine stimulation does not parallel sustained upregulation of GM-CSF-induced effector proteins and functions. This incomplete understanding of signaling maintenance from GM-CSF receptor, may explain why, to date, no therapeutic target has been established to successfully eliminate lung activated eosinophils in human trials. Our current investigations employ systematic proteomic analysis of: 1). In vivo and in vitro activated eosinophil, 2). Signaling pathways downstream of GM-CSF receptor, 3). Cross talk between signaling pathways/networks from growth factor and adhesion molecules in activated eosinophils. The research conducted in our lab is significant because incomplete understanding of mechanisms of eosinophil activation in adhesion dependent/cytokine independent manner is one major roadblock to developing anti-eosinophilic human asthma therapies. We are in unique position, having both access to high throughput proteomic analysis, bioinformatics resources and experience of investigating biology of human eosinophils. By identifying unique proteome of activated eosinophil and key molecules governing intracellular signaling, our studies have a potential for guiding the discovery of new eosinophil-specific signaling pathways and the rational development of cell/receptor specific therapies for modulation of eosinophilic/allergic inflammation.

Selected Publications

  1. Pazdrak K., Schreiber D., Forsythe P., Justement L. R. Alam. The intracellular signal transduction mechanism of interleukin 5 in eosinophils: the involvement of lyn tyrosine kinase and the ras-raf-1-mek-microtubule-associated protein kinase pathway. Journal of Experimental Medicine. 181 (5):1827-34, 1995.
  2. Pazdrak K., Justement L., Alam.R . Mechanism of inhibition of eosinophil activation by transforming growth factor-beta. Inhibition of Lyn, MAP, Jak2 kinases and STAT-1 nuclear factor. Journal of Immunology. 155(9):4454-8, 1995.
  3. Pazdrak K., Adachi T., Alam R. Src homology 2 protein tyrosine phosphatase (SHPTP2)/Src homology 2 phosphatase 2 (SHP2) tyrosine phosphatase is a positive regulator of the interelukin 5 receptor signal transduction pathways leading to prolongation of eosinophil survival. Journal of Experimental Medicine. 186(4):561-8, 1997.
  4. Olszewska-Pazdrak B., Pazdrak K., Ogra P.L. Garofalo R. Respiratory syncytial virus-infected pulmonary epithelial cells induce eosinophil degranulation by a CD18-mediated mechanism. Journal of Immunology. 160(10):4889-95, 1998.
  5. Gorski P. Krakowiak A, Pazdrak K, Palczynski C, Ruta U., Walusiak J. Nasal challenge test in the diagnosis of allergic respiratory diseases in subjects occupationally exposed to high molecular allergen (flour). Occupational Medicine (Oxford). 48(2):91-7, 1998.
  6. Krakowiak A., Gorski P., Pazdrak K., Ruta U. Airway response to formaldehyde inhalation in asthmatic subjects with suspected respiratory formaldehyde sensitization. American Journal of Industrial Medicine. 33(3):274-81, 1998.
  7. Pazdrak K., Olszewska-Pazdrak B., Stafford S., Garofalo R.P. Alam R. Lyn, Jak2, and raf-1 kinases are critical for the antiapoptotic effect of interleukin 5, whereas only raf-1 kinase is essential for eosinophil activation and degranulation. Journal of Experimental Medicine. 188(3):421-9, 1998.
  8. Adachi T., Pazdrak K., Stafford S., Alam R. The mapping of the Lyn kinase binding site of the common beta subunit of IL-3/granulocyte-macrophage colony-stimulating factor/IL-5 receptor. Journal of Immunology. 162(3):1496-501, 1999.
  9. Pazdrak K. Olszewska-Pazdrak B., Liu T., Takizawa R., Brasier A., Garofalo R. Casola A.: Raf-MAP Activation is Involved in Post Transcriptional Regulation of RSV-Induced RANTES Gene Expression. American Journal of Physiology Lung Cellular and Molecular Physiology. 2002 283(2):L364-72.
  10. Pazdrak K, X.Z. Shi, S.K. Sarna. TNFalpha suppresses human colonic circular smooth muscle contractility by SP1- and NF-kappaB-mediated induction of ICAM-1. Gastroenterology, 2004 Oct;127(4):1096-109.
  11. Shi XZ, Pazdrak K., Saada N., Dai B., Palade P., Sarna SK. Negative transcriptional regulation of human colonic smooth muscle Cav 1.2 channels by p50 and p65 subunits of nuclear factor kappa B. Gastroenterology 2005;129:1518-1532