A5068155775- Hearing, Cochlea, Tinnitus, Genetics
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- RNA regulation and disease
- Neurogenetic and Muscular Disorders Research
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Emergency and Acute Care Studies
- DNA Repair Mechanisms
- Disaster Response and Management
- BRCA gene mutations in cancer
- Hearing Loss and Rehabilitation
- Connexins and lens biology
- Ear Surgery and Otitis Media
- Cancer-related molecular mechanisms research
- Trauma and Emergency Care Studies
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Vestibular and auditory disorders
- Genetic Neurodegenerative Diseases
- Prenatal Screening and Diagnostics
- MicroRNA in disease regulation
- Alzheimer's disease research and treatments
- Antimicrobial Peptides and Activities
- melanin and skin pigmentation
Rosalind Franklin University of Medicine and Science
2011-2022
Apolipoprotein E receptor 2 (ApoER2) is an apolipoprotein involved in long-term potentiation, learning, and memory. Given its role cognition association with the Alzheimer's disease (AD) risk gene, apoE, ApoER2 has been proposed to be AD, though a for not clear. signaling requires amino acids encoded by alternatively spliced exon 19. Here, we report that balance of 19 splicing deregulated postmortem brain tissue from AD patients transgenic mouse model To test designed antisense...
The Parkinson disease (PD) genetic LRRK2 gain-of-function mutations may relate to the ER pathological changes seen in PD patients at postmortem. Human induced pluripotent stem cell (iPSC)-derived neurons with pathogenic G2019S mutation exhibited neurite collapse when challenged Ca2+ influx sarco/ER Ca2+-ATPase inhibitor thapsigargin (THP). Baseline levels measured indicator CEPIA-ER were lower human neurons, including differentiated midbrain dopamine vitro. After THP challenge,...
Abstract The BRCA1 tumor suppressor contributes to the repair of DNA double-strand breaks (DSB) through homologous recombination, but mechanism is unknown. rapid accumulation into nuclear foci in response induction suggests that may function an early step pathway. We examined role one such step, resection DSBs generate ssDNA. appearance ssDNA ionizing radiation similar formation, suggesting two processes are related. Furthermore, colocalizes sites induced by radiation. Overexpression causes...
There is at present no cure or effective therapy for spinal muscular atrophy (SMA), a neurodegenerative disease that the leading genetic cause of infant mortality. SMA usually results from loss SMN1 (survival motor neuron 1) gene, which leads to selective degeneration. SMN2 nearly identical but has nucleotide replacement causes exon 7 skipping, resulting in truncated, unstable version protein. all patients, and correcting splicing promising approach therapy. We identified tetracycline-like...
Spinal muscular atrophy (SMA) is a neurological disorder characterized by motor neuron degeneration and progressive muscle paralysis. The disease caused reduction in survival of (SMN) protein resulting from homozygous deletion the SMN1 gene. SMN also encoded SMN2. However, splicing SMN2 exon 7 defective, consequently, majority transcripts produce truncated, unstable protein. itself has role splicing. required for biogenesis spliceosomal snRNPs, which are essential components reaction. We now...
Spinal muscular atrophy (SMA) is one of the most common inherited causes pediatric mortality. SMA caused by deletions or mutations in survival motor neuron 1 (SMN1) gene, which results SMN protein deficiency. Humans have a centromeric copy SMN2, nearly identical to SMN1. However, SMN2 cannot compensate for loss SMN1 because has single-nucleotide difference exon 7, negatively affects splicing exon. As result, mRNA produced from lacks 7. lacking 7 encodes truncated with reduced functionality....
The absence of functional outer hair cells is a component several forms hereditary hearing impairment, including Usher syndrome, the most common cause concurrent and vision loss. Antisense oligonucleotide (ASO) treatment mice with human mutation, Ush1c c.216G>A, corrects gene expression significantly improves hearing, as measured by auditory-evoked brainstem responses (ABRs), well inner cell (IHC OHC) bundle morphology. However, it not clear whether improvement in achieved ASO involves...
Usher syndrome is a syndromic form of hereditary hearing impairment that includes sensorineural loss and delayed-onset retinitis pigmentosa (RP). Type 1 (USH1) characterized by congenital profound vestibular areflexia, with adolescent-onset RP. Systemic treatment antisense oligonucleotides (ASOs) targeting the human USH1C c.216G>A splicing mutation in knockin mouse model USH1 restores balance. Herein, we explore effect delivering ASOs locally to ear treat dysfunction associated syndrome....
Congenital diseases account for a large portion of pediatric illness. Prenatal screening and diagnosis permit early detection many genetic diseases. Fetal therapeutic strategies to manage disease processes in utero represent powerful new approach clinical care. A safe effective fetal pharmacotherapy designed modulate gene expression ideally would avoid direct mechanical engagement the fetus present an external reservoir drug. The amniotic cavity surrounding could serve as ideal drug...
Usher syndrome type 1C (USH1C/harmonin) is associated with profound retinal, auditory and vestibular dysfunction. We have previously reported on an antisense oligonucleotide (ASO-29) that dramatically improves function balance behavior in mice homozygous for the harmonin mutation Ush1c c.216G > A following a single systemic administration. The findings were suggestive of improved function; however, no direct assessment was made. Here, we measured sensory evoked potentials (VsEPs) to directly...
Disabling hearing loss impacts ∼466 million individuals worldwide with 34 children affected. Gene and pharmacotherapeutic strategies to rescue auditory function in mouse models of human deafness are most effective when administered before onset, after which therapeutic efficacy is significantly diminished or lost. We hypothesize that preemptive correction a mutation the fetal inner ear prior maturation sensory epithelium will optimally restore function. previously demonstrated transuterine...