A5033621010- Amyotrophic Lateral Sclerosis Research
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Neurogenetic and Muscular Disorders Research
- Neuroendocrine regulation and behavior
- Autism Spectrum Disorder Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Evolutionary Psychology and Human Behavior
- Neurogenesis and neuroplasticity mechanisms
- Ubiquitin and proteasome pathways
- Metal complexes synthesis and properties
- Prion Diseases and Protein Misfolding
- Infant Health and Development
- Cancer therapeutics and mechanisms
- Sleep and Wakefulness Research
- Genetic Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
- Tryptophan and brain disorders
- Alzheimer's disease research and treatments
- Muscle Physiology and Disorders
University of North Carolina at Chapel Hill
2014-2024
University of North Carolina Health Care
2022
New York State Office for People With Developmental Disabilities
2019
Indiana University School of Medicine
2013-2016
Technical University of Munich
2011-2012
Abbott (Sweden)
2011
Umeå University
2011
Abbott Fund
2011
Klinik für Frauenheilkunde
2007-2008
The heparan sulfate proteoglycan syndecan-1 (Sdc1) modulates cell proliferation, adhesion, migration and angiogenesis. Proteinase-mediated shedding converts Sdc1 from a membrane-bound coreceptor into soluble effector capable of binding the same ligands. In breast carcinomas, overexpression correlates with poor prognosis an aggressive phenotype. To distinguish between roles shed forms in cancer progression, human MCF-7 cells were stably transfected plasmids overexpressing wild-type (WT),...
The transcription factor c-Myc (or "Myc") is a master regulator of pathways driving cell growth and proliferation. MYC deregulated in many human cancers, making its downstream target genes attractive candidates for drug development. We report the unexpected finding that B-cell lymphomas from mice patients exhibit striking correlation between high levels Myc checkpoint kinase 1 (Chk1).By vitro biology studies as well preclinical using genetically engineered mouse model, we evaluated role Chk1...
Highlights•Mutation of Arc ubiquitination sites slows degradation•Arc knockin mice have enhanced mGluR-LTD•The persistence reduces cognitive flexibilitySummaryNeuronal activity regulates the transcription and translation immediate-early gene Arc/Arg3.1, a key mediator synaptic plasticity. Proteasome-dependent degradation tightly limits its temporal expression, yet significance this regulation remains unknown. We disrupted control by creating an mouse (ArcKR) where predominant were mutated....
Epidemiological studies suggest that heavy alcohol use early in life is associated with increased risk for Alzheimer's disease (AD). However, mechanisms connecting AD have not been identified. Both and feature proinflammatory signaling. Therefore, we hypothesized adolescent binge ethanol would increase molecular behavioral pathology adulthood through The 3xTg-AD mouse model (APPSwe, tauP301, Psen1tm1Mpm) which features amyloid (Aβ) tau beginning at 6-12 months underwent intermittent (AIE, 5...
Patients with autism spectrum disorder (ASD) experience high rates of sleep disruption beginning early in life; however, the developmental consequences this are not understood. We examined behavior and developing mice bearing C-terminal truncation mutation high-confidence ASD risk gene SHANK3 (Shank3ΔC). hypothesized that may be an sign divergence, clinically relevant Shank3WT/ΔC at increased lasting deleterious outcomes following life disruption.We recorded Shank3ΔC/ΔC, Shank3WT/ΔC,...
Social deficits are a hallmark feature of autism spectrum disorder (ASD) and related developmental syndromes. Although there is no standard treatment for social dysfunction, clinical studies have identified oxytocin as potential therapeutic with prosocial efficacy. We previously reported that peripheral can increase sociability ameliorate repetitive stereotypy in adolescent mice from the C58/J model ASD-like behavior. In present study, we determined effects were not limited to period, since...
Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, lack of speech, ataxia, EEG abnormalities, and epilepsy. Seizures in individuals with AS are common, debilitating, often drug resistant. Thus, there an unmet need for better treatment options. Cannabidiol (CBD), major phytocannabinoid constituent cannabis, has shown antiseizure activity behavioral benefits preclinical clinical studies some disorders associated epilepsy, suggesting that the same...
TDP-43 proteinopathies including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by aggregation mislocalization of the nucleic acid-binding protein subsequent neuronal dysfunction. Here, we developed endogenous models sporadic proteinopathy based on principle that disease-associated acetylation at lysine 145 (K145) alters conformation, impairs RNA-binding capacity, induces downstream mis-regulation target genes....
Mice with knockdown of the N-methyl-<smlcap>d</smlcap>-aspartate (NMDA) receptor NR1 subunit, encoded by gene <i>Grin1,</i> have been investigated as a model for intrinsic NMDA hypofunction hypothesized schizophrenia. Previous work has shown that adult <i>Grin1</i> mutant mice overt deficits in habituation and sensorimotor gating, exaggerated reactivity to environmental stimuli, reduced social approach, other alterations reflect behavioral manifestations...
TDP-43 proteinopathies including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by aggregation mislocalization of the nucleic acid-binding protein subsequent neuronal dysfunction. Here, we developed endogenous models sporadic proteinopathy based on principle that disease-associated acetylation at lysine 145 (K145) alters conformation, impairs RNA-binding capacity, induces downstream mis-regulation target genes....
LAMA2-related muscular dystrophy (LAMA2 MD) is the most common and fatal form of early-onset congenital dystrophies. Due to large size laminin α2 cDNA heterotrimeric structure protein, it challenging develop a gene-replacement therapy. Our group has developed novel adeno-associated viral (AAV) vector carrying mini-agrin, which non-homologous functional substitute for mutated α2. A significant therapeutic effect in skeletal muscle was observed our previous study using AAV serotype 1 (AAV1)....
Abstract Background Sleep is an essential process that supports brain health and cognitive function in part through the modification of neuronal synapses. disruption, impaired synaptic processes, are common features neurodegenerative diseases, including Alzheimer’s disease (AD). However, casual role sleep disruption progression not clear. Neurofibrillary tangles, made from hyperphosphorylated aggregated Tau protein, form one major hallmark pathologies seen AD contribute to decline, synapse...
Abstract Underlying drivers of late-onset Alzheimer’s disease (LOAD) pathology remain unknown. However, multiple biologically diverse risk factors share a common pathological progression. To identify convergent molecular abnormalities that drive LOAD pathogenesis we compared two midlife for LOAD, heavy alcohol use and obesity. This revealed disrupted lipophagy is an underlying cause pathogenesis. Both exposures reduced lysosomal flux, with loss neuronal acid lipase (LAL). resulted in lipid...
Sleep disruption and impaired synaptic processes are common features in neurodegenerative diseases, including Alzheimer's disease (AD). Hyperphosphorylated Tau is known to accumulate at neuronal synapses AD, contributing synapse dysfunction. However, it remains unclear how sleep pathology interact contribute cognitive decline. Here, we examined sex-specific onset consequences of loss AD/tauopathy model PS19 mice. Using a piezoelectric home-cage monitoring system, showed mice exhibited...
The Cks1 component of the SCF(Skp2) complex is necessary for p27(Kip1) ubiquitylation and degradation. expression elevated in various B cell malignancies including Burkitt lymphoma multiple myeloma. We have previously shown that loss results levels delayed tumor development a mouse model Myc-induced lymphoma. Surprisingly, Skp2 same also resulted but exhibited no impact on onset. This raises possibility could other oncogenic activities than suppressing p27(Kip1). To challenge this notion we...
Angelman syndrome (AS), a neurodevelopmental disorder associated with intellectual disability, is caused by loss of maternal allele expression UBE3A in neurons. Mouse models AS faithfully recapitulate disease phenotypes across multiple domains, including behavior. Yet AS, there has been only limited study behaviors encoded the prefrontal cortex, region broadly involved executive function and cognition. Because cognitive impairment core feature it critical to develop behavioral readouts...
In recent years, several genome-wide association studies have identified candidate regions for genetic susceptibility in major mood disorders. Most notable are a locus chromosome 3p21, encompassing the genes NEK4-ITIH1-ITIH3-ITIH4. Three of these represent heavy chains composite protein inter-α-inhibitor (IαI). order to further establish associations with disorders, we evaluated behavioral phenotypes mice deficient either Ambp/bikunin, which is necessary functional ITIH1 and ITIH3 complexes,...