Dr. Kisby received his doctoral degree in Pharmacology/Toxicology from the University of Texas in Austin. He was a laboratory instructor in the College of Pharmacy at the University of Texas and, subsequently, Research Associate in the Institute of Neurotoxicology, Albert Einstein College of Medicine in New York. Dr. Kisby has special expertise in analytical toxicology and neurotoxicology.

My laboratory is currently investigating the underlying molecular mechanisms of chronic neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). A central hypothesis under study in our laboratory is that nervous tissue DNA damage and DNA repair play important roles in the neurodegenerative disease process. Our previous work demonstrated a strong link between environmental exposure to a natural genotoxin (i.e., cycasin or methylazoxymethanol beta-D-glucoside) and a neurological disorder found in the western Pacific with features of ALS, parkinsonism and an Alzheimer-like dementia (western Pacific ALS/PDC). Current studies are examining the mechanism by which cycasin or methylazoxymethanol (MAM, the active metabolite) initiates neuronal cell death. Since this agent is a known genotoxin, we are using mice that overexpress or are defective in different DNA repair pathways to explore the relationship between DNA damage and neuronal cell death. Using primary murine neuronal cultures and murine stem cells, the long-term impact of DNA damage on neuronal function in the developing nervous system is being examined by profiling the gene expression patterns of both mature (i.e., post-mitotic) or immature (i.e., proliferating) neurons and glial cells treated with MAM. A combination of gene targeting strategies and the expression of different DNA repair fusion proteins are currently being used to examine the regulation of DNA repair within neurons and its influence by various environmental or endogenous agents. Other areas under development include determining if various environmental (e.g., diet, stress) or endogenous (e.g., aging) factors influence nervous tissue DNA repair.

Selected Publications

Meira, L.b., Devaraj, S., Kisby, G.E., Burns, D.K., Daniel, R.L., Hammer, R.E., Grundy, S., Jialal, I., and Friedberg, E.C. (2001) Heterozygosity for the mouse Apex gene results in phenotypes associated with oxidative stress. Cancer Research 61, 5552-5557.

Kisby, G.E., Springer, N., and Spencer, P.S. (2000) In vitro neurotoxic and DNA-damaging properties of nitrogen mustard (HN2). Journal of Applied Toxicology 20, S35-S41.

Spencer, P.S. Kisby, G.E., Palmer, V.S. and Obendorf, P. (2000) Cycasin, methylazoxymethanol, and related compounds. In: Experimental and Clinical Neurotoxicology, 2nd edition, (Spencer, P.S. and Schaumburg, H.H., eds. ), Oxford, New York, pp. 436-447.

Esclaire, F., Kisby, G.E., Milne, J., Lesort, M., Spencer, P., and Hugon, J. (1999) The Guam cycad toxin methylazoxymethanol damages neuronal DNA and modulates tau mRNA expression and excitotoxicity. Experimental Neurology 155,11-21.

Hugon, J., Esclaire, F., Lesort, M., Kisby, G.E., and Spencer, P.S. (1999) Toxic neuronal apoptosis and modifications of tau and APP gene and protein expressions. Drug Metabolism Reviews 31, 635-647.

Kisby, G.E., Kabel, H., Hugon, J., and Spencer, P.S. (1999) Damage and Repair of nerve cell DNA in toxic stress. Drug Metabolism Reviews 31, 589-618.