A5077386855- RNA regulation and disease
- Parkinson's Disease Mechanisms and Treatments
- MicroRNA in disease regulation
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Nuclear Receptors and Signaling
- Autism Spectrum Disorder Research
- Genomics and Chromatin Dynamics
- Neurological disorders and treatments
- Cancer-related molecular mechanisms research
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Microbial Metabolic Engineering and Bioproduction
- Muscle Physiology and Disorders
- Cancer-related gene regulation
- Genomic variations and chromosomal abnormalities
- Genetic Mapping and Diversity in Plants and Animals
- Genomics and Rare Diseases
- Insurance and Financial Risk Management
- Process Optimization and Integration
- Lysosomal Storage Disorders Research
- Firm Innovation and Growth
- Microbial Community Ecology and Physiology
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
Boston University
2010-2016
Constructor University
2007
Parkinson disease (PD) is a neurodegenerative characterized by the accumulation of alpha-synuclein (SNCA) and other proteins in aggregates termed "Lewy Bodies" within neurons. PD has both genetic environmental risk factors, while processes leading to aberrant protein aggregation are unknown, past work points abnormal levels SNCA proteins. Although several genome-wide studies have been performed for PD, these focused on DNA sequence variants association (GWAS) RNA (microarray...
Transcriptional dysregulation has long been recognized as central to the pathogenesis of Huntington's disease (HD). MicroRNAs (miRNAs) represent a major system post-transcriptional regulation, by either preventing translational initiation or targeting transcripts for storage degradation. Using next-generation miRNA sequencing in prefrontal cortex (Brodmann Area 9) twelve HD and nine controls, we identified five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-615-3p miR-1247-5p)...
Copy number variants (CNVs) are known to cause Mendelian forms of Parkinson disease (PD), most notably in SNCA and PARK2. PARK2 has a recessive mode inheritance; however, recent evidence demonstrates that single CNV (but not missense mutation) may increase risk for PD. We recently performed genome-wide association study PD excluded individuals have either LRRK2 mutation or two mutations. Data from the Illumina370Duo arrays were re-clustered using only white with high quality intensity data,...
The recent Parkinson Disease GWAS Consortium meta-analysis and replication study reports association at several previously confirmed risk loci SNCA, MAPT, GAK/DGKQ, HLA identified a novel locus RIT2. To further explore functional consequences of these associations, we investigated modification gene expression in prefrontal cortex brain samples pathologically PD cases (N = 26) controls 24) by 67 associated SNPs 5 loci. Association between the eSNPs was evaluated using 2-degrees freedom test...
MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression mainly through translational repression of target mRNA molecules. More than 2700 human miRNAs have been identified and some known to be associated with disease phenotypes display tissue-specific patterns expression. We used high-throughput small RNA sequencing discover novel in 93 post-mortem prefrontal cortex samples from individuals Huntington's (n = 28) or Parkinson's 29) controls without neurological impairment...
Genome-wide association studies (GWAS) have identified the GAK/DGKQ/IDUA region on 4p16.3 among top three risk loci for Parkinson's disease (PD), but specific gene and mechanism are unclear. Here, we report transcripts containing 3' clathrin-binding domain of GAK by RNA deep-sequencing in post-mortem human brain tissue as having increased expression PD. Furthermore, carriers PD GWAS SNPs show decreased one these transcripts, GAK25 (Gencode Transcript 009), which correlates with genes...
Metabolic engineering design methodology has evolved from using pathway-centric, random and empirical-based methods to systems-wide, rational integrated computational experimental approaches. Persistent during these advances been the desire develop strategies that address multiple simultaneous goals, such as maximizing productivity, while minimizing raw material costs. Here, we use constraint-based modeling systematically combinations of medium compositions gene-deletion strains for three...
Duplications and triplications of the α-synuclein ( SNCA ) gene increase risk for PD, suggesting increased expression levels to be associated with PD risk. However, past studies in brain tissue report inconsistent results. We examined full-length transcript (140 amino acid protein isoform), as well total mRNA 165 frontal cortex samples (101 64 control) using quantitative real-time polymerase chain reaction. Additionally, we evaluated relationship eight SNPs both 5′ 3′ regions levels. The...