A5101502575- Calpain Protease Function and Regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related molecular mechanisms research
- Genetic Mapping and Diversity in Plants and Animals
- Genetic and phenotypic traits in livestock
- Protease and Inhibitor Mechanisms
- Congenital heart defects research
- Atherosclerosis and Cardiovascular Diseases
- Barrier Structure and Function Studies
- Adipose Tissue and Metabolism
- MicroRNA in disease regulation
- Signaling Pathways in Disease
- Cardiomyopathy and Myosin Studies
- Tumors and Oncological Cases
- Cell Adhesion Molecules Research
- RNA Research and Splicing
- Immune Response and Inflammation
- Cardiac Fibrosis and Remodeling
- Ferroptosis and cancer prognosis
- Histiocytic Disorders and Treatments
- Cytokine Signaling Pathways and Interactions
- Neurological Disease Mechanisms and Treatments
- Vascular Malformations and Hemangiomas
Duke Medical Center
2013-2025
Duke University
2014-2023
Duke University Hospital
2013-2021
Laboratory of Molecular Genetics
2016
Sturge-Weber Syndrome (SWS) is a sporadic (non-inherited) syndrome characterized by capillary vascular malformations in the facial skin, leptomeninges, or choroid. A hallmark feature mosaic nature of phenotype. SWS caused somatic mutation GNAQ gene (p.R183Q), leading to activation G protein, Gαq. Decades ago, Rudolf Happle hypothesized as an example "paradominant inheritance", that is, "lethal (mutation) surviving mosaicism". He predicted "presence zygote will lead death embryo at early...
Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation. This process has been implicated in various diseases, including ischemic stroke. Ischemic stroke leads to oxidative stress, iron overload, and reactive oxygen species (ROS) accumulation, which collectively may trigger ferroptotic neuronal death. However, the regulatory mechanisms ferroptosis remain poorly understood. Previous studies have identified ataxia telangiectasia mutated (ATM), a DNA damage...
Identifying genetic variants that affect the level of cell cycle reentry and establishing degree progression in those could help guide development therapeutic interventions aimed at effecting cardiac regeneration. We observed C57Bl6/NCR (B6N) mice have a marked increase cardiomyocyte S-phase activity after permanent coronary artery ligation compared with infarcted DBA/2J (D2J) mice.
Risk for ischemic stroke has a strong genetic basis, but heritable factors also contribute to the extent of damage after occurred. We previously identified locus on distal mouse chromosome 7 that contributes over 50% variation in postischemic cerebral infarct volume observed between inbred strains. Here, we used ancestral haplotype analysis fine-map this 12 candidate genes. The gene encoding IL-21 receptor (Il21r) showed marked difference strain-specific transcription levels and coding...
During ischemic stroke, occlusion of the cerebrovasculature causes neuronal cell death (infarction), but naturally occurring genetic factors modulating infarction have been difficult to identify in human populations. In a surgically induced mouse model we previously mapped Civq1 distal chromosome 7 as quantitative trait locus determining infarct volume. this study, genome-wide association mapping using 32 inbred strains and an additional linkage scan for volume confirmed that size is...
Ischemic stroke caused by an embolus or local thrombosis results in neural tissue damage (an infarct) the territory of occluded cerebral artery. Decades studies have increased our understanding molecular events during infarction; however, translation these discoveries to druggable targets for ischemic treatment has been largely disappointing. Interleukin‐4 ( IL ‐4) is a multifunctional cytokine that exerts its cellular activities via interleukin‐4 receptor α ‐4Rα). This complex associated...
Abstract To identify genes involved in cerebral infarction, we have employed a forward genetic approach inbred mouse strains, using quantitative trait loci (QTL) mapping for infarct volume after middle artery occlusion. We had previously observed that is inversely correlated with collateral vessel density most strains. In this study, expanded the pool of allelic variation among classical strains by utilizing eight founder Collaborative Cross and found wild-derived strain, WSB/EiJ, breaks...
Although studies with inbred strains of mice have shown that infarct size is largely determined by the extent collateral vessel connections between arteries in brain enable reperfusion ischemic territory, we identified strain pairs do not vary this vascular phenotype, but which nonetheless exhibit large differences size. In study performed quantitative trait locus (QTL) mapping from an intercross two such strains, WSB/EiJ (WSB) and C57BL/6J (B6). This QTL revealed only one neuroprotective on...
Using the permanent middle cerebral artery occlusion (MCAO) model of stroke, we have demonstrated that different inbred mouse strains show profound differences in infarct volume, indicating infarction is under strong genetic control. To identify natural determinants modulating infarction, employed quantitative trait locus (QTL) linkage analysis and a genome-wide association study volume. We identified on distal chromosome 7 contributes over 50% variation as well other loci smaller effect....
Abstract To identify genes involved in cerebral infarction we have employed a forward genetic approach inbred mouse strains, using quantitative trait locus (QTL) mapping for infarct volume after middle artery occlusion. We had previously observed that is inversely correlated with collateral vessel density the strains. In this study, expanded pool of allelic variation among classical strains by utilizing eight founder Collaborative Cross and found wild-derived strain, WSB/EiJ, breaks general...
Abstract Ischemic stroke is caused by a disruption of the blood supply to brain leading neuronal cell death. Genetic studies ischemic have identified numerous gene variants that increase risk develop stroke. In stark contrast, genetic outcomes, such as infarct territory size, are confounded many uncontrollable variables, paucity targets for treatment an incipient Using genetically diverse inbred strains mice and surgically-induced model stroke, we used quantitative trait locus mapping...
Abstract Ischemic stroke, caused by vessel blockage, results in cerebral infarction; the death of brain tissue. Previously, quantitative trait locus mapping (QTL) infarct volume and collateral number identified a single, strong genetic regulating both phenotypes. Additional studies causative gene, encoding RAB GTPase Binding Effector Protein 2 ( Rabep2 ). However, there is yet no evidence that variation human ortholog this gene plays any role ischemic stroke outcomes. We established an vivo...