A5041356208- Automotive and Human Injury Biomechanics
- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Transportation Safety and Impact Analysis
- Traffic and Road Safety
- Genomics, phytochemicals, and oxidative stress
- Cell Adhesion Molecules Research
- Musculoskeletal pain and rehabilitation
- Lung Cancer Research Studies
- MicroRNA in disease regulation
- Cancer Research and Treatments
- Microtubule and mitosis dynamics
- Autonomous Vehicle Technology and Safety
- Genomics and Chromatin Dynamics
- Injury Epidemiology and Prevention
- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Circular RNAs in diseases
- ATP Synthase and ATPases Research
- Ubiquitin and proteasome pathways
- Traumatic Brain Injury Research
- Plant Molecular Biology Research
Washington University in St. Louis
2021-2025
University of North Carolina at Chapel Hill
2019-2023
UNC Lineberger Comprehensive Cancer Center
2019-2023
University of Michigan
1973-2023
Michigan United
2013
Human Pumilio proteins, PUM1 and PUM2, are sequence specific RNA-binding proteins that regulate protein expression. We used RNA-seq, rigorous statistical testing an experimentally derived fold change cut-off to identify nearly 1000 target RNAs-including mRNAs non-coding RNAs-that functionally regulated by PUMs. Bioinformatic analysis defined a PUM Response Element (PRE) was significantly enriched in transcripts increased abundance matches the consensus. created computational model...
Abstract Nuclear factor erythroid 2-related 2 (NFE2L2/NRF2) is a critical mediator of the cellular oxidative stress response. Aberrant activation NRF2 common in lung and upper aerodigestive cancers, where it promotes tumor initiation progression confers resistance to chemotherapy, radiation therapy, immune checkpoint inhibitors. As such, therapeutic inhibitors are actively being sought. We previously reported that antiparasitic drug Pyrimethamine (PYR) inhibits cell lines NRF2-inducible...
Mutant KRAS promotes mitosis by stimulating phosphorylation of the adaptor protein FADD.
Head-first free falls of 30 children, 1-10 yr old, and one adult, 21 were studied to determine fall circumstances injuries sustained. The six children adult simulated using the MVMA Two-Dimensional Crash Victim Simulator computer model. data show that head-first onto rigid surfaces from heights as low 2 m can result in serious injuries. Conservative head injury tolerance limits are estimated be 200-250g for peak acceleration.
In addition to their degradative role in protein turnover, proteases play a key as positive or negative regulators of signal transduction pathways and therefore dysregulation contributes many disease states. Regulatory roles include hormone-like triggering G protein-coupled signaling (Protease-Activated-Receptors); shedding ligands such EGF, Notch Fas; events that lead apoptotic cell death. Dysregulated activation apoptosis by the caspase family has been linked diseases cancer, autoimmunity...
Nuclear factor erythroid 2-related 2 (NFE2L2, also known as NRF2) is a transcription and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent recurrent in human cancer, but conversely NRF2 activity diminishes with age neurodegenerative metabolic disorders. Although NRF2-activating drugs are clinically beneficial, inhibitors do not yet exist. Here, we describe use gain-of-function genetic screen the kinome to identify new druggable regulators signaling. We found...
Abstract Lung squamous carcinoma (LUSC) is a highly metastatic disease with poor prognosis. Using an integrated screening approach, we found that miR-671-5p reduces LUSC metastasis by inhibiting circular RNA (circRNA), CDR1as. Although the putative function of circRNA through miRNA sponging, more potently silenced axis CDR1as and its antisense transcript, cerebellar degeneration related protein 1 (CDR1). Silencing or CDR1 significantly inhibited metastases was sufficient to promote migration...
Activation of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or NRF2) transcription is a critical and evolutionarily conserved cellular response to oxidative stress, metabolic xenobiotic insult. Deficiency NRF2 results in hypersensitivity variety stressors, whereas its aberrant activation contributes several cancer types, most commonly squamous cell carcinomas esophagus, oral cavity, bladder, lung. Between 10% 35% patients with display hyperactive signaling, harboring activating...
This paper presents the various features and operational properties of a two-dimensional mathematical model crash victim motions. The this include: (1) An eight mass representation human body where contact between vehicle is represented in terms independent force-deformation vehicle. (2) extensible multijoint neck realistically flexible shoulder joint. (3) A real- line interior or exterior shape given as network points. (4) Specific predictive restraint device submodels for airbag, energy...
During recent years, the Highway Safety Research Institute (HSRI) has developed and validated two- three-dimensional models describing motions forces acting upon an occupant during a collision. These inexpensive-to-operate are performing with approximately 90% accuracy in parametric studies of classical crash configurations. In our own validation procedures, contacts automobile development design groups, discussions federal agencies, certain shortcomings mathematical modeling procedures have...
Ovarian cancer is the fifth leading cause of cancer-related deaths among American women. Platinum-based chemotherapy, such as cisplatin, represents standard-of-care for ovarian cancer. However, toxicity and acquired resistance to cisplatin have proven challenging in treatment patients with cancer.Using a genetically engineered mouse model endometrioid adenocarcinoma (OEA) combination molecular-imaging technologies, we studied activation AKT serine/threonine kinase response long-term...
NRF2 is a master transcription factor that regulates the stress response. frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy radiation therapy. Therefore, great need exists for inhibitors targeted therapy of
Abstract Histone methyltransferases play essential roles in the organization and function of chromatin. They are also frequently mutated human diseases including cancer 1 . One such often methyltransferase, SETD2, associates co-transcriptionally with RNA polymerase II catalyzes histone H3 lysine 36 trimethylation (H3K36me3) – a modification that contributes to gene transcription, splicing, DNA repair 2 While studies on SETD2 have largely focused consequences its catalytic activity,...
A parameter study is performed involving several analytical vehicle occupant models in current use, with investigation of neck representations a primary goal. Side, oblique, and rear impact situations are investigated. Attention given to the effects varying head-neck mass moments inertia, anthropometry, muscle strength, location, as well strength motion-limiting stops. model that replaces conventional simple ball-joint two-joint, extensible studied. This also makes use joint-stop ellipses...
Aberrant activation or suppression of WNT/β-catenin signaling contributes to cancer initiation and progression, neurodegeneration, bone disease. However, despite great need more than 40 years research, targeted therapies for the WNT pathway have yet be fully realized. Kinases are considered exceptionally druggable occupy key nodes within network, but several pathway-relevant kinases remain understudied "dark." Here, we studied function casein kinase 1γ (CSNK1γ) subfamily human their roles in...
This study examined risk factors for injury, injury prevalence, safety gear use, and skating habits of adult recreational in-line skaters.Randomly selected skaters in 6 major US cities were interviewed.Only 6% consistently wore all 4 recommended types gear. Skaters with greater experience more likely to perform tricks, wear less gear, sustain an injury.More experienced are at increased injury. Safety use alarmingly low skaters, especially skaters. Safe education programs should consider...
Occupant response to side-impact collisions is studied with a mathematical vehicle/occupant model, the NVMA Two-Dimensional Crash Victim Simulator. A primary goal investigation of head-torso relative motion and neck forces moments. The subject pool consisted six carefully defined population segments which represented young, middle-age, elderly male female adults average stature. simulations make use much pertinent data resulting from volunteer testing program, including head-neck lateral...
Abstract Objective: NRF2 is a master transcription factor that regulates the stress response. frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy radiation therapy. Therefore, great need exists for inhibitors targeted therapy of NRF2high ESCC. Design: We performed high-throughput screening two compound libraries from hit compounds were further validated ESCC cells genetically modified mouse model. Mechanism action one...
Abstract NFE2L2/NRF2 is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent recurrent in human cancer, conversely NRF2 protein levels as well activity diminished with age neurodegenerative disorders. Though activating drugs are clinically beneficial, inhibitors do not yet exist. Here we used gain-of-function genetic screen the kinome to identify new druggable regulators signaling. We found that understudied kinase Brain Specific Kinase...