A5060903493- Genetic Associations and Epidemiology
- Alzheimer's disease research and treatments
- Autophagy in Disease and Therapy
- Parkinson's Disease Mechanisms and Treatments
- Bioinformatics and Genomic Networks
- Lysosomal Storage Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Calcium signaling and nucleotide metabolism
- Cellular transport and secretion
- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Genetic Mapping and Diversity in Plants and Animals
- Epigenetics and DNA Methylation
- Neurological Disorders and Treatments
- Tryptophan and brain disorders
- Endoplasmic Reticulum Stress and Disease
- Inflammation biomarkers and pathways
- Genetic Neurodegenerative Diseases
- MicroRNA in disease regulation
- Hypothalamic control of reproductive hormones
- BRCA gene mutations in cancer
- Adipose Tissue and Metabolism
- Pharmaceutical Economics and Policy
- Extracellular vesicles in disease
- Immune responses and vaccinations
University of Pennsylvania
2017-2020
Harvard University
2013-2018
Massachusetts General Hospital
2012-2018
Institute for Neurodegenerative Disorders
2018
The University of Texas Health Science Center at San Antonio
2018
Pfizer (United States)
2015-2018
Boston University
2018
Erasmus MC
2018
Framingham Heart Study
2018
Therapeutics Clinical Research
2015-2017
Aggregation of alpha-synuclein (αsyn) and resulting cytotoxicity is a hallmark sporadic familial Parkinson's disease (PD) as well dementia with Lewy bodies, recent evidence implicating oligomeric pre-fibrillar forms αsyn the pathogenic species. Recent in vitro studies support idea transcellular spread extracellular, secreted across membranes. The aim this study to characterize oligomers determine their extracellular location.Using novel protein fragment complementation assay where fused...
Parkinson’s disease (PD) is characterized pathologically by intraneuronal inclusions called Lewy bodies, largely comprised of α-synuclein. Multiplication the α-synuclein gene locus increases expression and causes PD. Thus, overexpression wild-type toxic. In this study, we demonstrate that impairs macroautophagy in mammalian cells transgenic mice. Our data show compromises autophagy via Rab1a inhibition rescues defect caused Inhibition or knockdown mislocalization protein, Atg9, decreases...
Exosomes are cellular secretory vesicles containing microRNAs (miRNAs). Once secreted, exosomes able to attach recipient cells and release miRNAs potentially modulating the function of cell. We hypothesized that exosomal miRNA expression in brains patients diagnosed with schizophrenia (SZ) bipolar disorder (BD) might differ from controls, reflecting either disease-specific or common aberrations SZ BD patients. The sources analyzed samples included McLean 66 Cohort Collection (Harvard Brain...
Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture AD among other populations is less understood.We conducted a transethnic genome-wide association study (GWAS) late-onset Stage 1 sample including Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by Disease Genetics Consortium. Suggestive results from novel were followed up using summarized International Genomics Project GWAS dataset.Genome-wide...
Autophagy is a lysosome-dependent cellular catabolic mechanism that mediates the turnover of intracellular organelles and long-lived proteins. Reduced autophagic activity has been shown to lead accumulation misfolded proteins in neurons might be involved chronic neurodegenerative diseases. Here, we uncover an essential role for syntaxin-5 SNARE complex autophagy. Using genetic knockdown, show regulates later stages autophagy after initial formation autophagosomes. This acts on by regulating...
Abstract Alzheimer’s disease (AD) therapeutics based on the amyloid hypothesis have shown minimal efficacy in patients, suggesting that activity of beta (Aβ) represents only one aspect AD pathogenesis. Since neuroinflammation is thought to play an important role AD, we hypothesized cytokines may a direct promoting neuronal death. Here, profiled cytokine expression small cohort human and control brain tissues. We identified AD-associated using partial least squares regression correlate with...
Abstract Introduction Variability exists in the disease trajectories of Alzheimer's (AD) patients. We performed a genome‐wide association study to examine rate cognitive decline (ROD) patients with AD. Methods tested for interactions between genetic variants and time since diagnosis predict ROD composite score 3946 AD cases pathway analysis on top genes. Results Suggestive associations ( P < 1.0 × 10 −6 ) were observed chromosome 15 DNA polymerase‐γ (rs3176205, = 1.11 −7 ), 7 (rs60465337,...
Purpose: This study aimed to evaluate early-phase safety of subretinal application AAVanc80.CAG.USH1Ca1 (OT_USH_101) in wild-type (WT) pigs, examining the effects a vehicle control, low dose, and high dose. Methods: Twelve WT pigs (24 eyes) were divided into three groups: four each received bilateral injections either vehicle, dose (3.3 × 1010 vector genomes [vg] per eye), or (1.0 1011 vg eye). Total retinal thickness (TRT) was evaluated using optical coherence tomography function assessed...
Autophagy has been implicated in various physiological and disease conditions recent years. A number of small molecule modulators have identified, both as tools potential therapeutics. Despite extensive characterization autophagy yeast, mammalian pathways are not fully understood. Recently, calcium phosphate precipitates (CPP), which used to transfect DNA into cells, were reported induce autophagy, when assayed up 6 h after treatment. Because the widespread use this reagent, we attempted...
A growing number of PSEN1 mutations have been associated with dementia Lewy bodies and familial Alzheimer's disease concomitant α-synuclein pathology. The objective this study was to determine if plays a direct role in the development pathology these diseases. Using mass spectrometry, immunoelectron microscopy fluorescence lifetime image based on Forster resonance energy transfer (FLIM-FRET) we identified as novel interactor wild-type mouse brain tissue. interaction detected post-mortem...
Mutations in the glucocerebrosidase (GBA) gene are known to be a risk factor for Parkinson's disease (PD). Data on clinicopathological correlation limited. The purpose of this study was determine findings that might distinguish PD cases with and without mutations GBA gene.Data from Arizona Study Aging Neurodegenerative Disorders were used identify autopsied did or not have mutation. Clinical neuropathological data compared.Twelve had mutation 102 not. died younger (76 vs. 81 years age) but...
Through a targeted recruitment 23andMe has collected DNA and patient-reported symptoms from more than 10,000 subjects reporting physician-verified diagnosis of PD. This study evaluated the potential self-report, web-based questionnaires to rapidly assess disease natural history symptomology in genetically-defined PD populations. While average age-at-diagnosis was significantly lower GBA mutation carriers compared idiopathic PD, or iPD (idiopathic defined as no mutations LRRK2 G2019S...
The transition from vegetative growth to reproductive is carefully controlled by a number of independent signal transduction systems, one which interprets photoperiod. Photoperiodic control flowering time has been well-described in Arabidopsis and rice, revealing the presence generally common network regulatory proteins. Timely appropriate progression critical profitable production cultivated strawberry ( Fragaria × ananassa ), species that includes long-day, short-day, day-neutral...