A5051644824- Amyotrophic Lateral Sclerosis Research
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA regulation and disease
- Neurotransmitter Receptor Influence on Behavior
- Muscle Physiology and Disorders
- Chemical synthesis and alkaloids
- Glioma Diagnosis and Treatment
- Psychedelics and Drug Studies
- Trace Elements in Health
- Nuclear Structure and Function
- Single-cell and spatial transcriptomics
- Endoplasmic Reticulum Stress and Disease
- Genetic Neurodegenerative Diseases
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- Metabolism and Genetic Disorders
- Ubiquitin and proteasome pathways
- Biochemical Acid Research Studies
- Dementia and Cognitive Impairment Research
Mayo Clinic in Arizona
2021-2024
WinnMed
2022-2024
Barrow Neurological Institute
2019-2023
Mayo Clinic in Florida
2022
Amyotrophic Lateral Sclerosis (ALS), is a fatal neurodegenerative disorder, with TDP-43 inclusions as major pathological hallmark. Using Drosophila model of proteinopathy we found significant alterations in glucose metabolism including increased pyruvate, suggesting that modulating glycolysis may be neuroprotective. Indeed, high sugar diet improves locomotor and lifespan defects caused by motor neurons or glia, but not muscle, metabolic dysregulation occurs the nervous system. Overexpressing...
Abstract The most common inherited cause of two genetically and clinico-pathologically overlapping neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD), is the presence expanded GGGGCC intronic hexanucleotide repeats in C9orf72 gene. Aside from haploinsufficiency toxic RNA foci, another non-exclusive disease mechanism non-canonical translation repeat into five different dipeptide proteins (DPRs), which form neuronal inclusions affected patient brains....
While motor and cortical neurons are affected in C9orf72 amyotrophic lateral sclerosis frontotemporal dementia (ALS/FTD), it remains largely unknown if how non-neuronal cells induce or exacerbate neuronal damage. We differentiated ALS/FTD patient-derived induced pluripotent stem into microglia (iPSC-MG) examined their intrinsic phenotypes. Similar to iPSC neurons, iPSC-MG mono-cultures form G 4 C 2 repeat RNA foci, exhibit reduced protein levels, generate dipeptide proteins. Healthy control...
Abstract The choroid plexus, a tissue responsible for producing cerebrospinal fluid, is found predominantly in the lateral and fourth ventricles of brain. This highly vascularized ciliated made up specialized epithelial cells capillary networks surrounded by connective tissue. Given complex structure this can potentially result contamination during routine dissection. Bulk single-cell RNA sequencing studies, as well genome-wide situ hybridization experiments (Allen Brain Atlas), have...
Disruption in copper homeostasis causes a number of cognitive and motor deficits. Wilson's disease Menkes are neurodevelopmental disorders resulting from mutations the transporters ATP7A ATP7B, with also causing occipital horn syndrome, distal neuropathy. A 65 year old male presenting brachial amyotrophic diplegia diagnosed lateral sclerosis (ALS) was found to harbor p.Met1311Val (M1311V) substitution variant ATP7A. ALS is fatal neurodegenerative associated progressive muscle weakness,...
Abstract Psilocybin is a psychedelic tryptamine that has emerged as potential candidate for the treatment of variety conditions, including resistant depression and post-traumatic stress disorder. Clinical trials which have assessed efficacy psilocybin these conditions report rapid sustained improvement in patient- clinician-rated scores. The established mechanism action psychedelics such agonism serotonin 2A receptor (5HT R), however, downstream events mediate their therapeutic effects...
Summary While motor and cortical neurons are affected in C9orf72 ALS/FTD, it remains still largely unknown if how non-neuronal cells induce or exacerbate neuronal damage. We generated ALS/FTD patient-derived induced pluripotent stem differentiated into microglia (iPSC-MG) examined their intrinsic phenotypes. Similar to iPSC neurons, iPSC-MG mono-cultures form G 4 C 2 repeat RNA foci, exhibit reduced protein levels generate dipeptide proteins. Healthy control equivalently express microglial...
Lewy body dementia and Alzheimer's disease (AD) are leading causes of cognitive impairment, characterized by distinct but overlapping neuropathological hallmarks. (LBD) is alpha-synuclein aggregates in the form bodies as well deposition extracellular amyloid plaques, with many cases also exhibiting neurofibrillary tangle (NFT) pathology. In contrast, plaques tangles. Both conditions often co-occur additional changes, such vascular TDP-43 To elucidate shared molecular signatures underlying...
Abstract Amyotrophic Lateral Sclerosis (ALS), is a fatal neurodegenerative disorder, with TDP-43 inclusions as major pathological hallmark. Using Drosophila model of proteinopathy we found significant alterations in glucose metabolism including increased pyruvate, suggesting that modulating glycolysis may be neuroprotective. Indeed, high sugar diet improves locomotor and lifespan defects caused by motor neurons or glia, but not muscle, metabolic dysregulation occurs the nervous system....
Abstract Background Lewy body dementia (LBD) is one of the most common causes and characterized by deposition extracellular amyloid plaques intracellular accumulation alpha‐synuclein in form bodies neurites. Many these individuals also have concomitant neuropathological changes such as vascular disease, tangles, TDP‐43. Like Alzheimer’s APOE4 significant genetic risk factor for development LBD. We sought to survey landscape transcriptional cingulate cortex from a large cohort LBD cases...
Abstract Glioblastoma (GBM), the most common primary brain tumor in adults, remains uniformly fatal due to lack of effective targeted therapies for this aggressive malignancy. Genomic amplification epidermal growth factor receptor (EGFR) occurs 40-60% GBM. Half all EGFR-amplified cases GBM also harbor EGFRvIII, a constitutively active, truncated variant EGFR. The incidence EGFR alterations makes inhibition EGFR/EGFRvIII an attractive therapeutic approach. Depatuxizumab mafodotin (ABT-414) is...