The Neurogenetics Laboratory is engaged in the identification and understanding of genetic factors that influence diseases and conditions of mid- and late life. The primary targets of our investigations are Huntington’s disease (HD), Parkinson’s disease (PD), and obesity, although we also study pulmonary function, cardiovascular disease, and osteoporosis.
Our research paradigms apply methodologies which combine five main areas of expertise:
- Genetic epidemiological studies into the patterns of disease expression in families and communities, examining the influence and interaction of genetic and environmental risk factors influencing disease risk.
- Genome-wide analysis of DNA sequence polymorphisms by “genome wide association studies” (GWAS), gene expression profiling by RNA-sequencing, and regulatory mechanisms by genome wide micro-RNA sequencing and by genome wide chromatin immunoprecipitation sequencing (ChIP-Seq), to identify genes, gene expression and regulatory mechanisms associated with disease risk.
- Statistical genetic methods to analyze and model the association of disease related phenotypes with the various components of genetic information described above.
- Bioinformatic assessment of gene sets and pathways as well as gene structure and function to gain insight into the genetic mechanisms implicated in disease expression.
- Cell biology and model organism studies of implicated genes and pathways to elucidate the mechanisms of disease expression and targets for therapeutic intervention.
The application of a variety of genetic analytic methods of the targeted traits and diseases is a major emphasis of the lab.
The lab has a long-standing interest in Huntington’s disease and participated in the cloning of the gene for Huntington’s disease in 1993, as well as a wide range of research investigations for this disease. We have been affiliated with the New England Huntington’s disease “Center Without Walls” since its inception in 1980. Our HD studies are best characterized as ‘Neurobiological Studies’ in that they encompass investigations into the mechanisms of disease expression, including complex genetic modifier studies and a series of neuropathological studies of effects of disease expression in the brain.
We initiated the genetic linkage scan project in the Framingham Study, and a genetic linkage and GWAS scans in Parkinson’s disease. Our Parkinson’s disease genetic study, known as the “GenePD” study, involved an international collaboration of more than twenty clinical centers in Parkinson’s disease.
Currently, the lab is engaged in studies of mRNA, sncRNA and ChIP Sequencing to elucidate the roles of genes and regulation of gene expression in neurodegeneration with an emphasis on Huntington’s disease and Parkinson’s disease. Our studies implicating GAK in alpha-synuclein toxicity in PD models, led to award of R01-NS076843-02 (Characterization of the Role of cyclin G-Associated Kinase in Parkinson disease, Myers PI) which focuses on RNA-Sequencing in PD and control brains. We recently initiated a combined ChIP-Sequencing / RNA-Sequencing study in Huntington’s and control brains which led to award of R01-NS073947-02 (Epigenetic Markers in Huntington Disease Brain, Myers PI).
NIH Funding Support:
R01-NS073947 (Epigenetic Markers in Huntington Disease Brain, Myers PI)
R01-NS076843 (Characterization of the Role of cyclin G-Associated Kinase in Parkinson disease, Myers PI)
R01-HL088215 (Genomic Scan for Atherosclerosis Pathway Genes in African Americans from FHS-SCAN, Michael A. Province PI, Myers Subcontract PI)
R01-AR/AG-41398 (Risk Factors for Age Related Bone Loss in the Framingham Study, Douglas Kiel PI, Myers Investigator)
Foundation Funding Support:
The Jerry MacDonald Huntington Disease Research Fund
The Coogan Family Research Fund for Parkinson’s disease
The Robert P. and Judith N. Goldberg Parkinson Research Foundation