Research Assistant Professor of Neurology
Phone: (412) 648-9154
Specialized Areas of Interest
Molecular genetics of neurodegenerative diseases
Eric K. Hoffman, PhD, is initiating investigations to further define the role of oxidative damage in the neurodegenerative process associated with Parkinson’s disease. Efforts are underway to develop fluorescent biomarkers capable of detecting oxidative stress within cells using fluorescence resonance energy transfer (FRET) analysis. These DNA constructs are composed of the enhanced yellow fluorescent protein (EYFP) gene fused to the enhanced cyan fluorescent protein (ECFP) gene with an oxidation sensitive peptide derived from the thioredoxin gene separating EYFP and ECFP. It is anticipated that under physiologically normal conditions the ECFP protein will fluoresce due to FRET excitation via the adjacent EYFP protein. Upon oxidation of the disulfide bond in the thioredoxin peptide, the fluorescent proteins should undergo a conformational change such that the required distance for FRET excitation of ECFP (50-100 Angstroms) is exceeded, leading to a loss of ECFP fluorescence. Proof of concept experiments using this system are in progress. Once validated, this methodology will be a valuable asset in the study of cell culture and animal models of oxidative stress and neurodegeneration. Other studies in progress are aimed at elucidating the roles of transferrin and the transferrin receptor 2 proteins and mitochondria in oxidative stress and neuronal cell death. Efforts are underway to overexpress and reduce the expression of the transferrin receptor 2 gene in order to better understand the possible association of this protein with iron-induced oxidative damage in neurons. Dr. Hoffman has recently published the results of a study entitled “A Genome-wide Search for Alcoholism Susceptibility Genes” in the American Journal of Medical Genetics. Two additional manuscripts that describe the role dopaminergic and GABAergic genes play in predisposition to alcoholism have been submitted for publication.
In the 2006-2007 academic year, Dr. Hoffman plans to continue his research efforts on the mechanisms of oxidative stress and neurodegeneration. Studies will focus on the use of inducible gene expression systems and RNA interference methods as a means to further define the function of proteins that have been implicated in the etiology of Parkinson’s disease.
Dr. Hoffman's publications can be reviewed through the National Library of Medicine's publication database.