We are interested in the function of lipids in both the normal nervous system (signal transduction, receptor expression) and in the dysfunctioning nervous system (inherited storage diseases, autoimmune diseases and hypoxia).

Most of our work uses either cell lines of nervous system origin into which we have stably transfected, by electroporation of DNA constructs, the receptors we are studying (serotonin or opioid), primary cultures (embryonic chick neurons or rat oligodendrocytes) or lymphoblastoid cell
lines from patients with inherited storage diseases.

We are interested in the role of lipids in stabilizing stress-sensitive receptors such as the 5HT1A serotonin and the opioid d2 and k1 subtypes and influencing their coupling to G-protein-mediated signal transduction pathways (phospholipases and adenylate cylases).   All three receptors have been cloned and our approach is to transfect the cDNA for these receptors into cells with different lipid compositions and look for both changes in lipids and different coupling.  We are also interested in the mechanism by which opioids (and insulin) are able to generate the diacylglycerol necessary to activate a specific protein kinase C isoform (e) involved ingrowth and development during a pre-apoptotic phase of embryonic chick neuronal development.

In addition, a series of studies on the response of differentiating oligodendrocytes to hypoxia has led from initial observations of the inhibition of synthesis of specific myelin lipids and proteins and the turning off of some signal transduction syustmes (e.g.: phospholipase C) to the induction of ferritin in these cells by oxygen deprivation.   We employ all the tools of biochemistry and molecular biology to elucidate the fundamental mechanisms involved in these processes.

Our third model for stress-induced neural damage involves naturally-occurring human mutations in lysosomal hydrolases.  To study this we immortalize the patient's lymphocytes, PCR amplify the cDNA for the enzyme protein of interest and determine the point mutation responsible for the enzyme deficiency.  In this way we are constructing a structure-function map of ß-hexosaminidase, an enzyme whose deficiency causes Tay Sachs disease when completely deficient and motor neuron disease (Lou Gehrig's disease phocopy) when partially deficient. 

Dawson, G., Dawson, S.A. and Goswami, R. (1997) Chronic exposure to kappa opioids enhances the susceptibility of immortalized neurons (F-11k7) to apoptosis-inducing drugs by a mechanism that involves ceramide. J.Neurochem., 68:2363-2370.

 Wiesner, D., Kilkus, J., Gottschalk, A.R., Quintans, J., and Dawson, G. (1997) Anti-immunoglobulin-induced apoptosis in WEHI-231 cells involves the slow formation of ceramide from sphingomyelin and is blocked by bclxL. J. Biol. Chem, 272:9868-9846.

 Mangoura, D.M., and Dawson, G. (1998) Programmed cell death in cortical chick embryo astrocytes is associated with activation of protein kinase PK60 and ceramide formation. J. Neurochem., 70:130-138.

 Goswami, R., Dawson, S.A., and Dawson, G. (1998) Cyclic AMP protects against staurosporine and wortmannin-induced apoptosis and opioid-enhanced apoptosis in both embryonic and immortalized (F-11k7) neurons. J. Neurochem., 70:

 Blackman, S.C., Dawson, G., Antonakis, K., and leBreton, G.C. (1998) The identification and characterization of oligodendrocyte thromboxane A2 receptors. J. Biol. Chem., 273:475-483.