A5025445829- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- Muscle Physiology and Disorders
- Pituitary Gland Disorders and Treatments
- Immune Response and Inflammation
- Synthesis and biological activity
- Neuroscience and Neuropharmacology Research
- Neonatal Health and Biochemistry
- Alzheimer's disease research and treatments
- Cannabis and Cannabinoid Research
- Hereditary Neurological Disorders
- Inflammatory mediators and NSAID effects
- Immune cells in cancer
- Biomedical Ethics and Regulation
- Cholinesterase and Neurodegenerative Diseases
- Cerebrospinal fluid and hydrocephalus
- Axon Guidance and Neuronal Signaling
- Ocular Diseases and Behçet’s Syndrome
- Antibiotics Pharmacokinetics and Efficacy
- Pharmacological Receptor Mechanisms and Effects
- Digital Media and Visual Art
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Synthesis and Reactions of Organic Compounds
- Esophageal and GI Pathology
Capital Health
2023-2024
Regional Medical Center
2024
University of Copenhagen
2021
Hospital Vozandes
2021
University of British Columbia
2010-2018
Child and Family Research Institute
2012-2018
Family Research Institute
2016
Okanagan University College
2010-2014
Rutgers New Jersey Medical School
2007-2008
Rutgers, The State University of New Jersey
2007-2008
Autosomal dominant diseases such as Huntington's disease (HD) are caused by a gain of function mutant protein and/or RNA. An ideal treatment for these is to selectively suppress expression the allele while preserving wild-type variant. RNase H active antisense oligonucleotides (ASOs) or small interfering RNAs can achieve selective suppression gene targeting single nucleotide polymorphisms (SNPs) associated with repeat expansion. ASOs have been previously shown discriminate changes in...
Huntington disease (HD) is a dominant, genetic neurodegenerative characterized by progressive loss of voluntary motor control, psychiatric disturbance, and cognitive decline, for which there currently no disease-modifying therapy. HD caused the expansion CAG tract in huntingtin (HTT) gene. The mutant HTT protein (muHTT) acquires toxic functions, significant evidence that muHTT lowering would be therapeutically efficacious. However, wild-type (wtHTT) serves vital making allele-specific...
Mutant huntingtin suppression with antisense oligonucleotides reverses cognitive impairments in a mouse model of Huntington’s disease.
Huntington disease (HD) model mice with heterozygous knock-in (KI) of an expanded CAG tract in exon 1 the mouse huntingtin (Htt) gene homolog genetically recapitulate mutation that causes HD, and might be favoured for preclinical studies. However, historically these have failed to phenotypically human disease. Thus, homozygous KI mice, which lack wildtype Htt, are much less relevant been used. The zQ175 was first exhibit significant HD-like phenotypes when heterozygous. In effort exacerbate...
Abstract Quantitation of huntingtin protein in the brain is needed, both as a marker Huntington disease (HD) progression and for use clinical gene silencing trials. Measurement cerebrospinal fluid could be biomarker huntingtin, but traditional quantitation methods have failed to detect fluid. Using micro-bead based immunoprecipitation flow cytometry (IP-FCM), we developed highly sensitive mutant detection assay. The sensitivity IP-FCM enables accurate HD patients model mice, demonstrating...
Huntington disease (HD) is an inherited, fatal neurodegenerative with no disease-modifying therapy currently available. In addition to characteristic motor deficits and atrophy of the caudate nucleus, signature hallmarks HD include behavioral abnormalities, immune activation, cortical white matter loss. The identification validation novel therapeutic targets that contribute these degenerative cellular processes may lead new interventions slow or even halt course this insidious disease....
Silencing the mutant huntingtin gene (muHTT) is a direct and simple therapeutic strategy for treatment of Huntington disease (HD) in principle. However, targeting HD mutation presents challenges because it an expansion common genetic element (a CAG tract) that found throughout genome. Moreover, HTT protein important neuronal health life, silencing strategies also reduce wild-type allele may not be well tolerated during long-term HD. Several are development target sites outside expansion,...
Huntington disease (HD) is a neurodegenerative caused by mutation in the huntingtin (HTT) gene. HTT large protein, interacts with many partners and involved cellular pathways, which are perturbed HD. Therapies targeting directly likely to provide most global benefit. Thus there need for preclinical models of HD recapitulating human genetics. We previously generated humanized mouse model HD, Hu97/18, intercrossing BACHD YAC18 mice knockout endogenous homolog (Hdh). Hu97/18 recapitulate...
Oxidative stress is a prominent feature of Huntington disease (HD), and we have shown previously that reduced levels hace1 (HECT domain Ankyrin repeat containing E3 ubiquitin protein ligase 1) in patient striatum may contribute to the pathogenesis HD. Hace1 promotes stability Nrf2 thus plays an important role antioxidant response mechanisms, which are dysfunctional Moreover, overexpression mitigates mutant huntingtin (mHTT)-induced oxidative vitro through promotion response. Here, show...
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human genetic polymorphism. The protects against malaria but was shown to worsen the clinical course after severe trauma. This study tested whether associated with altered cytokine responses in vitro and vivo affects survival endotoxemia or polymicrobial sepsis (cecal ligation puncture).Genotyping of animals carried out using novel improved allele-specific polymerase chain reaction assay. Macrophage splenocyte ex were compared...
Abstract Bone marrow (BM) dysfunction is an important component of immunomodulation. This study investigated alterations in cell content, apoptotic responses, and proliferation BM, blood, spleen endotoxemic mice (LPS from Escherichia coli). As the decreased antioxidant status associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to modulate innate immune response, we also tested whether a G6PD mutation (80% decrease cellular enzyme activity) alters BM responses...
Abstract Disclosure: G. Wintermyer: None. E. Villanueva: Oftentimes, Graves and Myasthenia Gravis present with very similar symptoms. This can complicate diagnoses of either. At the same time, cause thymic hyperplasia, there is a link between thymoma. In following, we discuss case that presented all three: 59-year-old female PMHx hyperlipidemia, GERD, hoarseness, anxiety developed sudden diplopia, unintentional weight loss, tremor, palpitation, ptosis for approximately one week. She had an...
Abstract Disclosure: S.Y. Rizvi: None. E. Villanueva: Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting many reproductive-age women, characterized by irregular menstrual cycles, hirsutism, and challenges with fertility. In this case study, we delve into the medical history of 24-year-old female presenting PCOS-related symptoms, infertility, unraveling multifaceted aspects her healthcare journey. Case Description: This patient's diagnostic path began when...
Parkinson's disease (PD) manifests in motor dysfunction, non-motor symptoms, and eventual dementia (PDD). Neuropathological hallmarks include nigrostriatal neurodegeneration, Lewy body (LB) pathology, neuroinflammation. Alpha-synuclein (α-syn), a primary component of LBs, is implicated PD pathogenesis, accumulating, aggregating both familial sporadic PD. However, as α-syn pathology often comorbid with amyloid-beta (Aβ) plaques phosphorylated tau (pTau) tangles PDD, it still unclear whether...
Huntington disease (HD) is a dominant, genetic neurodegenerative characterized by progressive loss of voluntary motor control, psychiatric disturbance, and cognitive decline, for which there currently no disease-modifying therapy. HD caused the expansion CAG tract in huntingtin (HTT) gene. The mutant HTT protein (muHTT) acquires toxic functions, significant evidence that muHTT lowering would be therapeutically efficacious. However, wild-type (wtHTT) serves vital making allele-specific...
Abstract Disclosure: G. Wintermyer: None. C. Arcilla: E. Villanueva: Autoimmune polyglandular syndrome type II (APS II) is a rare combination of multiple endocrine diseases. The most common associated diseases are diabetes I, Hashimoto thyroiditis, and Addison’s disease. Most patients present with nonspecific symptoms, typically in adulthood. Here we describe 19-year-old female APS II:A history depression presented to hospital severe nausea, vomiting chest pain. She was diagnosed...