Research 

About the Robert Guthrie Molecular Genetics Research Laboratory

The Robert Guthrie Molecular Genetics Research Laboratory is a sister laboratory to the clinical diagnostics laboratory. The research laboratory performs clinical and basic research in the School of Medicine & Biomedical Sciences at the University at Buffalo.
In addition to the Director, Dr. Georgirene Vladutiu, the research laboratory is staffed by Dr. Paul Isackson, Technical Director and Research Associate Professor of Pediatrics, Mrs. Shanping Huang, M.S., Research Technologist, and Ms. Catherine Kern, Research Assistant.  

Dr. Isackson is an accomplished scientist and molecular biologist with more than 80 publications in areas that include the regulation of expression of neurotrophic factors, protein kinases, and novel mutation detection in metabolic muscle diseases. Dr. Isackson has contributed significantly to our laboratory in the identification of more than 35 mutations causing disorders such as carnitine palmitoyltransferase (CPT) II deficiency, McArdle disease, myoadenylate deaminase deficiency and very long-chain acylCoA dehydrogenase deficiency. Dr. Isackson also performs ongoing genotype/phenotype correlations for these and other disease-causing mutations.
Mrs. Huang performs a variety of molecular analyses including SNP analysis in genome-wide association studies, DNA mutation screening in research study participants, statistical analysis of laboratory data, and database management. Mrs. Huang maintains the laboratory’s compliance records for institutional review board requirements.

Ms. Kern is the research study coordinator and serves as the liaison between patient participants, physician-scientist collaborators, and laboratory staff. She also maintains our participant information databases.

Ongoing Research Studies

Statin-Induced Myopathy Study

The benefits of statins are undisputed in reducing the risk of coronary heart disease and the progression of coronary atherosclerosis. Nevertheless, associated complications can be life-threatening. More than 38 million people in the U.S. will be taking statins by the end of 2008. Up to 7% (>2.6 million) will develop muscle symptoms and up to 0.5% (>190,000) may develop life-threatening myopathies. Our long-term goal is to identify clinically significant genetic variants associated with statin myopathy. Our hypothesis is that susceptibility to statin myopathy is complex and will include an increased prevalence of underlying hereditary muscle disorders as well as genetic variation in genes with broad regulatory roles in cellular metabolism and structure. This hypothesis is based on preliminary findings of significantly increased mutant alleles causative for 3 common metabolic myopathies in patients with statin myopathy vs. statin-tolerant patients (p=0.04). Up to 20- and 13-fold increases in mutant allele frequencies exist for McArdle disease and carnitine palmitoyltransferase II deficiency, respectively. Aim 1 will expand the number of candidate disorders and mutations evaluated in patients with statin myopathies.  Aim 2 will identify and characterize clinically significant associations between single nucleotide polymorphisms and statin myopathies in a case-control genome-wide association study using microarray analysis.

Funding: This and related projects are funded by grants from the National Heart, Lung, and Blood Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH

Study Participants: Any person who has taken a statin drug and developed severe myopathic or neuromyopathic side effects during therapy may enter the study (Test Participants). We also need participants who take statin drugs and have no muscle side effects (Control Participants). Potential participants in this study should contact Cathy Kern at 716-829-2695, Tuesday through Friday from 8AM until 4PM.

Statin Study Forms

• Statin-Induced Myopathy Flyer
• Statin-Induced Myopathy Consent Form
• Statin-Tolerant Control Consent Form
• Statin-Induced Myopathy Saliva Consent
• HIPAA Consent Form
• Statin Study Questionnaire

Publications by RGBGL staff