Research

 Robert Guthrie Biochemical & Molecular Genetics Laboratory  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 Jacobs School of Medicine & Biomedical Sciences at the University at Buffalo.

In addition to the Director, Dr. Georgirene Vladutiu, Dr. Paul Isackson, Technical Director and Research Associate Professor of Pediatrics, performs molecular research studies in the laboratory.

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 50 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.

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 40 million people are taking statins in the U.S. 10-15% of them will develop muscle symptoms and up to 0.5% (200,000) may develop life-threatening muscle disease. 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 was originally based on preliminary findings of significantly increased mutant alleles causative for 3 common metabolic myopathies in patients with severe 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. Employing whole exome and whole genome sequencing, we have expanded the number of candidate disorders and pathogenic variants evaluated in patients with statin myopathies and have found underlying genetic risk for a number of additional disorders. Manuscripts are in preparation describing our findings.

Funding: This and related projects have been funded by grants from the National Heart, Lung, and Blood Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, and the Paul J. Rich, Jr and Doris Miller Rich Research Fund.

Study Participants: Recruitment of participants for this study is closed at this time. We are in the process of performing the final analysis of data accrued.

Publications by RGBGL staff