ApoE mimetic ameliorates motor deficit and tissue damage in rat spinal cord injury.

The overall interest of my laboratory is to identify the underlying causes of neurodegenerative diseases such as Alzheimer's disease. Once causes or experimental endpoints are determined, then strategies to find chemicals which can ameliorate pathophysiological events can be devised. In general, we are working to create transgenic animals and validate them as models of human disease.

Our specific approach has been to study the function of apolipoprotein-E (apoE) which Roses and colleagues found to a susceptibility factor for the presence of AD. Currently, our data are pointing to a relationship between apoE and oxidative stress where apoE appears to modulate nitric oxide production in a species specific manner. To further test this idea, we have created transgenic mice expressing the entire human NOS2 gene which will now be tested in various models of neurodegeneration and inflammation. Similarly, we are developing transgenic animals which express the human TAU gene. When properly stressed, these TAU-transgenic animals may display the neurofibrillary tangle pathology which is associated with neurodegeneration in a wide variety of neurological diseases.

If our transgenic animals prove to be validated models of human
disease, then the process to screen for chemicals which might alter the disease outcome in those models can begin in earnest. Should compounds be identified, then the various phases of clinical trials may proceed.

At present, my community service includes participation on the Alzheimer's Association Medical and Scientific Advisory Board and on the Neurological Sciences III Study Section for the National Institutes of Health extramural research program. I have previously served in a similar capacity for the American Health Assistance Foundation and the Long Island Alzheimer's Foundation. I have also had the pleasure to serve as a scientific consultant for various biotechnology companies.

Keywords: Neurodegeneration, Alzheimer's, Transgenic, Animal Models, Amyloid, Apolipoprotein-E, Molecular Biology, Biochemistry

We have successfully developed various rodent models of brain and spinal cord injuries in our lab, such as focal cerebral ischemia, global cerebral ischemia, head trauma, subarachnoid hemorrhage, intracerebral hemorrhage, spinal cord ischemia and compression injury. We also established cardiac arrest and hemorrhagic shock models for studying multiple organ dysfunction.  Our current studies focus on two projects. One is to examine the efficacy of catalytic antioxidant in treating cerebral ischemia and the other is to examine the efficacy of post-conditioning on outcome of subarachnoid hemorrhage induced cognitive dysfunction.