A5014713306- Hearing, Cochlea, Tinnitus, Genetics
- Hearing Loss and Rehabilitation
- Vestibular and auditory disorders
- RNA modifications and cancer
- RNA Research and Splicing
- RNA regulation and disease
- Acoustic Wave Phenomena Research
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- RNA and protein synthesis mechanisms
- Lipid Membrane Structure and Behavior
- Mitochondrial Function and Pathology
- Machine Learning in Bioinformatics
- Histone Deacetylase Inhibitors Research
- GABA and Rice Research
- Cardiac Valve Diseases and Treatments
- Adenosine and Purinergic Signaling
- Enzyme Structure and Function
- Calcium signaling and nucleotide metabolism
- Signaling Pathways in Disease
- Visual perception and processing mechanisms
- Animal Vocal Communication and Behavior
- Pulmonary Hypertension Research and Treatments
- Biochemical and Molecular Research
- Ubiquitin and proteasome pathways
Harvard University
2007-2022
Eaton (United States)
2018-2022
Massachusetts Eye and Ear Infirmary
2018-2022
Rockefeller University
2019
Brigham and Women's Hospital
2007-2016
Tufts University
2010-2015
Tufts Medical Center
2010
University of Richmond
2006
Mammalian stress granules (SGs) contain stalled translation preinitiation complexes that are assembled into discrete by specific RNA-binding proteins such as G3BP. We now show cells lacking both G3BP1 and G3BP2 cannot form SGs in response to eukaryotic initiation factor 2α phosphorylation or eIF4A inhibition, but still SG-competent when challenged with severe heat osmotic stress. Rescue experiments using mutants G3BP1-F33W, a mutant unable bind G3BP partner Caprin1 USP10, rescues SG...
When exposed to continuous high-level noise, cochlear neurons are more susceptible damage than hair cells (HCs): exposures causing temporary threshold shifts (TTS) without permanent HC can destroy ribbon synapses, permanently silencing the they formerly activated. While this "hidden hearing loss" has little effect on thresholds in quiet, neural degeneration degrades noise and may be an important elicitor of tinnitus. Similar sensory pathologies seen after blast injury, even if shift (PTS) is...
Abstract Overexposure to intense noise can destroy the synapses between auditory nerve fibers and their hair cell targets without destroying cells themselves. In adult mice, this synaptopathy is immediate largely irreversible, whereas, in guinea pigs, counts of immunostained synaptic puncta recover with increasing post-exposure survival. Here, we asked whether recovery simply reflects changes immunostaining, or there actual retraction extension neurites and/or synaptogenesis. Analysis...
Noise exposures causing only transient threshold shifts can destroy auditory-nerve synapses without damaging hair cells. Here, we asked whether virally mediated neurotrophin3 (NT3) overexpression repair this damage. CBA/CaJ mice at 6 wks were injected unilaterally with adeno-associated virus (AAV) containing either NT3 or GFP genes, via the posterior semicircular canal, 3 prior to, 5 hrs after, noise exposure. Controls included exposed animals receiving vehicle only, and unexposed virus....
In CBA/CaJ mice, confocal analysis has shown that acoustic overexposure can immediately destroy synapses between auditory-nerve fibers (ANFs) and their peripheral targets, the inner hair cells (IHCs), years later, a corresponding number of ANF cell bodies degenerate. guinea pig, post-exposure disappearance pre-synaptic ribbons be equally dramatic, however, recovery to near-baseline counts been reported. Since are confounded by thresholding issues, fall rise synaptic ribbon could represent...
Meniere's disease (MD), a degenerative inner ear disorder, is characterized by debilitating episodic vertigo "attacks" and hearing fluctuations, progressing to permanent sensory impairment. The prevailing dogma attributes these symptoms an abnormal fluid buildup, known as endolymphatic hydrops (EH), with concomitant rise of pressure repetitive microtrauma epithelia. However, this pressure-based mechanism lacks direct experimental evidence fails explain key clinical aspects MD - exposing...
Normal hearing requires proper differentiation of afferent ribbon synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) that carry acoustic information to the brain. Within individual IHCs, presynaptic ribbons show a size gradient with larger on modiolar face smaller pillar face. This structural is associated spontaneous rates threshold sensitivity, which essential for wide dynamic range hearing. Despite their importance hearing, mechanisms direct are poorly defined. We...
Pulmonary artery hypertension (PAH) is characterized by elevated pulmonary resistance and increased medial thickness due to deregulation of vascular remodeling. Inactivating mutations the BMPRII gene, which encodes a receptor for bone morphogenetic proteins (BMPs), are identified in ∼60% familial PAH (FPAH) ∼30% idiopathic (IPAH) patients. It has been hypothesized that constitutive reduction BMP signal may cause abnormal remodeling promoting dedifferentiation smooth muscle cells (vSMCs)....
Higher Eukaryotic Glutamate Dehydrogenases show complex allosteric regulation. More primitive eukaryotes and prokaryotes have glutamate dehydrogenases that while calalyzing the same reaction no, or very limited, regulatory properties. Data mining of a wide variety dehydrogenase sequences structures has led to insights into structure function relationships in this important enzyme forms basis current experimental investigations. By examining comparing amino acid Dehydrogenase both higher we...