The process by which hormones, drugs and growth factors induce shortlived responses and longterm alterations in various cells is a rapidly growing research area. Elucidation of the detailed molecular mechanisms underlying these processes is expected to reveal important information on receptor function, and to provide new approaches for the design of treatment modalities for various diseases. In my laboratory we are investigating the biochemical pathways of cellular activation in two different cell systems: the human platelet and the neuron.
Our studies with human platelets focus on the process whereby interaction of an agonist with its receptors leads to the exposure of active fibrinogen binding sites at the platelet surface, resulting in platelet aggregation and vesicular secretion. We have isolated a monoclonal antibody that acts as an agonist and activates platelets. Currently we are completing the following investigations: 1)the purification of the surface protein(s) which serves as antigen for this antibody, 2)initiation of the cloning of the gene for this receptor protein, and 3)the identification of the biochemical pathways involved in its action. These studies are expected to add a new dimension to the understanding of molecular mechanisms which regulate homeostatic responses to vascular injury.
In parallel studies, we are investigating the interactions of the extracellular-mediator, the alkyether phospholipid PlateletActivatingFactor (PAF), with the nervous system, using cloned neuronal cell lines and primary CNS neurons grown and differentiated in culture. We have found that PAF activates receptoroperated calcium channels in neuron. By increasing intracellular freecalcium levels, low concentrations of PAF induce neurite extension, whereas higher concentrations of PAF are neurotoxic. Presently we are investigating the role of PAF in neuronal development and we are examining the exciting possibility that PAFantagonistic drugs can protect neurons from the irreversible degeneration induced during trauma, stroke and spinal cord injury.
RECENT PUBLICATIONS
Kornecki, E., Cooper, B. A. and Ehrlich, Y. H. 1988. Identification of a Unique Type of Thrombopathy of Human Platelets: Defect in the exposure of active fibrinogen receptors in a patient with Friedreich's Ataxia. J. Lab. Clin. Med. 111:618626.
Kornecki, E., Ehrlich, Y. H., Egbring, R., Gramse, M., Seitz, R., Eckardt, A., Lukasiewicz, H., Niewiarowski, S. 1988. GranulocytePlatelet Interactions and Platelet Fibrinogen Receptor Exposure. Amer. J. Physiol. 255:H 651 H658.
Kornecki, F., and Ehrlich, Y. H. 1988. Neuroregulatory and Neuropathological Actions of the eitherphospholipid PlateletActivating factor, Science 240:19721974.
Kornecki, F., Walkowiak, B., Naik, U. P. and Fhrlich, Y. H. 1990. Activation of Human Platelets by a Stimulatory Monoclonal Antibody. J. Biol. Chem. 265:1004210048.
ELIZABETH KORNECKI, Ph.D.
Associate Professor
Department of Anatomy and Cell Biology
Phone: 270-2377/4049, Fax: 270-3732
E-mail: ekornecki@downstate.edu
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