Overview
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
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
Current Appointments & Affiliations
Adjunct Associate Professor in Neurology
·
2015 - Present
Neurology, Behavioral Neurology,
Neurology
Recent Publications
Apolipoprotein E4 and Alzheimer's disease causality under adverse environments and potential intervention by senolytic nutrients.
Journal Article Clinical nutrition ESPEN · December 2024 Apolipoprotein E (apoE) has a pivotal role in Alzheimer's Disease (AD) pathophysiology. APOE4 has been recognized as a risk factor for developing late-onset AD. Recently, APOE4 homozygosity was regarded as a new familial genetic trait of AD. In this opinio ... Full text CitePros and Cons of APOE4 Homozygosity and Effects on Neuroplasticity, Malnutrition, and Infections in Early Life Adversity, Alzheimer's Disease, and Alzheimer's Prevention.
Journal Article Journal of Alzheimer's disease : JAD · January 2024 Fortea et al.'s. (2024) recent data analysis elegantly calls attention to familial late-onset Alzheimer's disease (AD) with APOE4 homozygosity. The article by Grant (2024) reviews the factors associated with AD, particularly the APOE genotype and lifestyle ... Full text CiteApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers.
Journal Article Pharmaceutics · March 2023 Apolipoprotein E (apoE) mimetic peptides are engineered fragments of the native apoE protein's LDL-receptor binding site that improve the outcomes following a brain injury and intestinal inflammation in a variety of models. The vicious cycle of enteric inf ... Full text CiteRecent Grants
A Mouse Model of Inflammation in Alzheimer's Disease
ResearchCo Investigator · Awarded by National Institutes of Health · 2009 - 2014The amyloid cascade in a novel mouse model of Alzheimer's disease
ResearchCo Investigator · Awarded by National Institutes of Health · 2009 - 2014Immune Responsiveness, APOE/Gender in Neurodegeneration
ResearchCo Investigator · Awarded by National Institutes of Health · 2004 - 2009View All Grants
Education, Training & Certifications
Dartmouth College ·
1983
Ph.D.