A5077861340- Amyotrophic Lateral Sclerosis Research
- Virus-based gene therapy research
- Viral Infections and Immunology Research
- Neurogenetic and Muscular Disorders Research
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Pluripotent Stem Cells Research
- Biochemical Acid Research Studies
- RNA modifications and cancer
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Macrophage Migration Inhibitory Factor
- Biotechnology and Related Fields
- Neuroinflammation and Neurodegeneration Mechanisms
- Prion Diseases and Protein Misfolding
- RNA and protein synthesis mechanisms
- Biomedical Ethics and Regulation
- Metabolism and Genetic Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- RNA regulation and disease
- Nuclear Receptors and Signaling
- Autism Spectrum Disorder Research
- Cytomegalovirus and herpesvirus research
- Muscle Physiology and Disorders
University of Missouri
2024-2025
Nationwide Children's Hospital
2021-2024
Industrial University of Santander
2016-2023
Fundación Cardiovascular de Colombia
2019-2023
RNA helicases constitute a large protein family implicated in cellular homeostasis and disease development. Here, we show that the helicase IGHMBP2, linked to neuromuscular disorder spinal muscular atrophy with respiratory distress type 1 (SMARD1), associates polysomes impacts translation of mRNAs containing short, GC-rich, structured 5′ UTRs. The absence IGHMBP2 causes ribosome stalling at start codon target mRNAs, leading reduced efficiency. main mRNA targets IGHMBP2-mediated regulation...
Repeat expansions in the C9ORF72 gene are a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Considerable progress has been made identifying C9ORF72-mediated disease resolving its underlying etiopathogenesis. The contributions intrinsic mitochondrial deficits as well chronic endoplasmic reticulum stress to development C9ORF72-linked pathology established. Nevertheless, date, no cure or effective therapy is available, thus attempts find potential drug target,...
Abstract Patient diversity and unknown disease cause are major challenges for drug development clinical trial design amyotrophic lateral sclerosis (ALS). Transgenic animal models do not adequately reflect the heterogeneity of ALS. Direct reprogramming patient fibroblasts to neuronal progenitor cells subsequent differentiation into astrocytes allows rapid generation relevant cell types. Thus, this methodology can facilitate compound testing in a diverse genetic background resulting more...
Neutralizing antibody (NAb) activity against the viral capsid of adeno-associated (AAV) vectors decreases transduction efficiency, thus limiting transgene expression. Several reports have mentioned a variation in NAb prevalence according to age, AAV serotype, and, most importantly, geographic location. There are currently no specifically describing anti-AAV Latin America. Here, we describe different serotypes (AAV1, AAV2, and AAV9) Colombian patients with heart failure (HF) (referred as...
The neurodevelopmental disorder Pitt Hopkins syndrome (PTHS) causes clinical symptoms similar to Rett (RTT) patients. However, RTT is caused by MECP2 mutations whereas in the TCF4 gene lead PTHS. mechanistic commonalities underling these two disorders are unknown, but their shared symptomology suggest that convergent pathway-level disruption likely exists. We reprogrammed patient skin derived fibroblasts into induced neuronal progenitor cells. Interestingly, we discovered MeCP2 levels were...
Spinal Muscular Atrophy (SMA) is the leading genetic cause of infant mortality. The most common form SMA caused by mutations in SMN1 gene, located on 5q (SMA). On other hand, IGHMBP2 lead to a large disease spectrum with no clear genotype-phenotype correlation, which includes Distress type 1 (SMARD1), an extremely rare SMA, and Charcot-Marie-Tooth 2S (CMT2S). We optimized patient-derived vitro model system that allows us expand research pathogenesis gene function, as well test response AAV...
Anc80L65 is a synthetic, ancestral adeno-associated virus that has high tropism toward retinal photoreceptors after subretinal injection in mice and non-human primates. We characterized, for the first time, post-intravitreal cell-specific transduction profile of compared with AAV9. Here we use AAV9 to intravitreally deliver copy gene encoding GFP into WT C57Bl/6J mice. expression was driven by one two clinically relevant promoters, chicken β actin (CB) or truncated MECP2 (P546). After...
Research on neurological disorders focuses primarily the impact of neurons disease mechanisms. Limited availability animal models severely impacts study cell type specific contributions to disease. Moreover, usually do not reflect variability in mutations and courses seen human patients. Reprogramming methods for generation induced pluripotent stem cells (iPSCs) have revolutionized patient research created valuable tools studying However, iPSC technology has disadvantages such as time, labor...
<title>Abstract</title> Repeat expansions in the <italic>C9ORF72</italic> gene are a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Considerable progress has been made identifying <italic>C9ORF72</italic>-mediated disease resolving its underlying etiopathogenesis. The contributions intrinsic mitochondrial deficits as well chronic endoplasmic reticulum stress to development C9ORF72-linked pathology is established, Nevertheless, date, no cure or effective...
Research on neurological disorders focuses primarily the impact of neurons disease mechanisms. Limited availability animal models severely impacts study cell type specific contributions to disease. Moreover, usually do not reflect variability in mutations and courses seen human patients. Reprogramming methods for generation induced pluripotent stem cells (iPSCs) have revolutionized patient research created valuable tools studying However, iPSC technology has disadvantages such as time, labor...
RNA helicases constitute a large protein family implicated in cellular homeostasis and disease development. Here we show that the helicase Ighmbp2, linked to neuromuscular disorder SMARD1 associates with polysomes impacts on translation of mRNAs containing short, GC-rich highly structured 5’UTRs. Absence Ighmbp2 causes ribosome stalling at start codon target mRNAs, leading their reduced efficiency. The main mRNA targets Ighmbp2mediated regulation encode for components THO complex link...