A5102908864- Traumatic Brain Injury Research
- Genetics, Aging, and Longevity in Model Organisms
- Pain Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Tryptophan and brain disorders
- RNA and protein synthesis mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- CRISPR and Genetic Engineering
- Identity, Memory, and Therapy
- RNA modifications and cancer
- Anesthesia and Neurotoxicity Research
- RNA Research and Splicing
- Congenital heart defects research
- Cancer Genomics and Diagnostics
- Sleep and related disorders
- Resilience and Mental Health
- Botulinum Toxin and Related Neurological Disorders
- Epigenetics and DNA Methylation
- S100 Proteins and Annexins
- Computational Drug Discovery Methods
- RNA regulation and disease
- Molecular spectroscopy and chirality
- Extracellular vesicles in disease
- Genomics and Rare Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
2014-2025
National Institutes of Health
2014-2025
Predict (France)
2022-2024
Johns Hopkins University
2023-2024
Digestive Care (United States)
2022
National Institute of Nursing Research
2016-2021
Uniformed Services University of the Health Sciences
2017
Walter Reed Army Institute of Research
2017
Naval Medical Research Command
2017
United States Army Medical Research and Development Command
2017
Experimental findings suggest that oligomeric forms of the amyloid β protein (Aβ) play a critical role in Alzheimer's disease. Thus, elucidating their structure and mechanisms formation is for developing therapeutic agents. We use discrete molecular dynamics simulations four-bead model to study oligomerization two predominant alloforms, Aβ40 Aβ42, at atomic level. The incorporates backbone hydrogen-bond interactions amino acid-specific mediated through hydrophobic hydrophilic elements side...
Pathological sensations caused by peripheral painful neuropathy occurring in Type 2 diabetes mellitus (T2DM) are often described as 'sharp' and 'burning' commonly spontaneous origin. Proposed etiologies implicate dysfunction of nociceptive sensory neurons dorsal root ganglia (DRG) induced generation reactive oxygen species, microvascular defects, ongoing axonal degeneration regeneration. To investigate the molecular mechanisms contributing to diabetic pain, DRGs were acquired postmortem from...
Translocon clogging at the endoplasmic reticulum (ER) as a result of translation stalling triggers ribosome UFMylation, activating translocation-associated quality control (TAQC) to degrade clogged substrates. How cells sense UFMylation initiate TAQC is unclear. We conduct genome-wide CRISPR-Cas9 screen identify an uncharacterized membrane protein named SAYSD1 that facilitates TAQC. associates with Sec61 translocon and also recognizes both UFM1 directly, engaging stalled nascent chain ensure...
Abstract Diabetic peripheral neuropathy (DPN) is characterized by spontaneous pain in the extremities. Incidence of DPN continues to rise with global diabetes epidemic. However, there remains a lack safe, effective analgesics control this chronic painful condition. Dorsal root ganglia (DRG) contain soma sensory neurons and modulate signal transduction into central nervous system. In study, we aimed gain deeper understanding changes molecular pathways DRG patients pain. We recently reported...
<h3>Objective:</h3> To explore gene expression after moderate blast exposure (vs baseline) and proteomic changes moderate- low-) exposure. <h3>Methods:</h3> Military personnel (N = 69) donated blood for quantification of protein level, peak pressure exposures were detected by helmet sensors before during a training program (10 days total). On day 7, some participants (n 29) sustained (mean 7.9 psi) matched to with no/low-blast the 40). PAXgene tubes collected from one site at baseline 10;...
Posttraumatic stress disorder (PTSD) is associated with wide-spread immune dysregulation; however, little known about the gene expression differences attributed to each PTSD symptom cluster. This an important consideration when identifying diagnostic and treatment response markers in highly comorbid populations mental physical health conditions that share symptoms. To this aim, we utilized a transcriptome-wide analysis of differential peripheral blood by comparing military service members:...
Bone morphogenetic proteins (BMPs) belong to the transforming growth factor β (TGFβ) superfamily of secreted molecules. BMPs play essential roles in multiple developmental and homeostatic processes metazoans. Malfunction BMP pathway can cause a variety diseases humans, including cancer, skeletal disorders cardiovascular diseases. Identification factors that ensure proper spatiotemporal control signaling is critical for understanding how this regulated. We have used unique sensitive genetic...
Over four hundred different microRNAs (miRNAs) have been identified in the genome of model organism nematode Caenorhabditis elegans. As germline is dedicated to preservation each species, and almost half all cells an adult are germline, it likely that regulatory miRNAs important for development maintenance. In C. elegans miR35 family has strong maternal effects, contributing normal embryogenesis fecundity. To determine whether any particular greatly enriched we used RNA-seq compare miRNA...
Patients who had a mild ischaemic stroke present with subtle or resolving symptoms sometimes go undiagnosed, are excluded from treatment and in some cases clinically worsen. Circulating immune cells potential biomarkers that can assist diagnosis stroke. Understanding the transcriptomic changes of each cell population caused by is critical because they work closely complicated relationship. In this study, we investigated peripheral blood mononuclear (PBMCs) transcriptomics patients using...
Ribosome stalling during co-translational translocation at the ER causes translocon clogging and impairs protein biogenesis. Mammalian cells resolve via a poorly characterized translocation-associated quality control (TAQC) process. Here, we combine genome-wide CRISPR screen with live-cell imaging to dissect molecular linchpin of TAQC. We show that TAQC substrates translated from mRNAs bearing ribosome-stalling poly(A) sequence are degraded by lysosomes proteasome. By contrast, degradation...
Whole-genome sequencing is a powerful tool for analyzing genetic variation on global scale. One particularly useful application the identification of mutations obtained by classical phenotypic screens in model species. Sequence data from mutant strain aligned to reference genome, and then variants are called generate list candidate alleles. A number software pipelines mutation have been targeted C. elegans, with particular emphasis ease use, incorporation mapping data, subtraction background...
Abstract Autoimmune diseases such as rheumatoid arthritis (RA) can promote states of chronic inflammation with accompanying tissue destruction and pain. RA cause inflammatory synovitis in peripheral joints, particularly within the hands feet, but also sometimes trigger temporomandibular joint (TMJ) arthralgia. To better understand effects ongoing inflammation-induced pain signaling, dorsal root ganglia (DRGs) were acquired from individuals for transcriptomic study. We conducted RNA...
Heme-iron recycling from senescent red blood cells (erythrophagocytosis) accounts for the majority of total body iron in humans. Studies cultured have ascribed a role HRG1/SLC48A1 heme-iron transport but vivo function this heme transporter is unclear. Here we present genetic evidence zebrafish model that Hrg1 essential macrophage-mediated during erythrophagocytosis kidney. Furthermore, show Hrg1a and its paralog Hrg1b are functional transporters, ablation both transporters double knockout...
Excessive accumulation of amyloid beta (Aβ) and tau have been observed in older individuals with chronic neurological symptoms related to a traumatic brain injury (TBI), yet little is known about the possible role Aβ younger active duty service members following TBI. The purpose study was determine if 40 or 42 sustaining TBI young cohort military personnel.This cross-sectional who reported provided self-report psychological blood.An ultrasensitive single-molecule enzyme-linked immunosorbent...
Nutrient-driven O-GlcNAcylation has been linked to epigenetic regulation of gene expression in metazoans. In C. elegans, O-GlcNAc marks the promoters over 800 developmental, metabolic, and stress-related genes; these marked genes show a strong 5', promoter-proximal bias distribution RNA Polymerase II (Pol II). response starvation or feeding, steady state at remain nearly constant presumably due dynamic cycling mediated by transferase OGT-1 O-GlcNAcase OGA-1. However, viable mutants lacking...
Military personnel experience posttraumatic stress disorder (PTSD), which is associated with differential DNA methylation across the whole genome. However, relationship between these patterns and clinically relevant increases in PTSD severity not yet clearly understood. The purpose of this study was to identify differences symptoms investigate changes related military personnel. In pilot study, a cross-sectional comparison made (n = 8) combat-matched controls without 6). Symptom measures...
Next generation sequencing produces base calls with low quality scores that can affect the accuracy of identifying simple nucleotide variation calls, including single polymorphisms and small insertions deletions. Here we compare effectiveness two data preprocessing methods, masking trimming, on whole-genome sequence from Caenorhabditis elegans. Masking substitutes 'N's (undetermined bases), whereas trimming removes bases results in a shorter read lengths. We demonstrate is more effective...
Blast exposure is common in military personnel during training and combat operations, yet biological mechanisms related to cell survival function that coordinate recovery remain poorly understood. This study explored how moderate blast influences gene expression; specifically, gene-network changes following exposure. On day 1 (baseline) of a 10-day program, blood samples were drawn, health demographic information collected. Helmets equipped with bilateral sensors worn throughout measured...
The Mediterranean diet (MD) has been reported to have beneficial effects on breast cancer and cardiovascular diseases. Recently, microRNAs (miRNAs) suggested as biomarkers for the diagnosis disease prognosis in We evaluated influence of MD plasma-derived extracellular vesicle miRNA signature overweight survivors. Sixteen participants instructed adhere eight weeks were included this study. To curate differentially expressed miRNAs after intervention, we employed two methods: significance...
Repetitive low-level blast exposure is one of the major occupational health concerns among US military service members and law enforcement. This study seeks to identify gene expression using microRNA RNA sequencing in whole-blood samples from experienced breachers unexposed controls. We performed experimental Illumina’s HiSeq 2500 Sequencing System, analysis NanoString Technology nCounter miRNA panel total 15 14 age-, sex-, race-matched identified 10 significantly dysregulated genes between...