- Developmental Biology and Gene Regulation
- RNA modifications and cancer
- Cancer-related gene regulation
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Fatty Acid Research and Health
- Muscle activation and electromyography studies
- Pluripotent Stem Cells Research
- Prosthetics and Rehabilitation Robotics
- Esophageal Cancer Research and Treatment
- Cancer-related molecular mechanisms research
- Total Knee Arthroplasty Outcomes
- Diabetic Foot Ulcer Assessment and Management
- TGF-β signaling in diseases
- MicroRNA in disease regulation
- Cancer Cells and Metastasis
- Dietary Effects on Health
- Kruppel-like factors research
- Mechanisms of cancer metastasis
- Drug-Induced Adverse Reactions
- Diet and metabolism studies
- Regulation of Appetite and Obesity
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Bacterial Infections and Vaccines
- Chemotherapy-related skin toxicity
West Virginia University
2022
University of Louisville
2022
University of Miami
2011-2017
Sylvester Comprehensive Cancer Center
2011-2017
Molecular Oncology (United States)
2011-2017
Wake Forest University
2006-2013
Winston-Salem/Forsyth County Schools
2009
Institute of Molecular Medicine
2007
University of Washington Medical Center
1995
Over the past 100 years, changes in food supply Western nations have resulted alterations dietary fatty acid consumption, leading to a dramatic increase ratio of omega-6 (ω6) ω3 polyunsaturated acids (PUFA) circulation and tissues. Increased ω6/ω3 ratios are hypothesized inflammatory mediator production, higher incidence diseases, may impact gene expression. To determine effect reducing on expression pathway genes mononuclear cells, healthy humans were placed controlled diet for 1 week, then...
Esophageal adenocarcinoma ranks sixth in cancer mortality the world and its incidence has risen dramatically Western population over last decades. Data presented herein strongly suggest that Notch signaling is critical for esophageal underlies resistance to chemotherapy. We present evidence drives a stem cell phenotype by regulating genes establish stemness. Using patient-derived xenograft models, we demonstrate inhibition of gamma-secretase inhibitors (GSI) efficacious downsizing tumor...
Abstract In many cancers, aberrant Notch activity has been demonstrated to play a role in the initiation and maintenance of neoplastic phenotype cancer stem cells, which may allude its additional involvement metastasis resistance therapy. Therefore, is an exceedingly attractive therapeutic target cancer, but full range potential targets within pathway underexplored. To date, there are no small-molecule inhibitors that directly intracellular or assembly transcriptional activation complex....
Abstract Background Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic (SDA, 18:4n-3) α (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic (AA) metabolism improve disorders. Methods The diet of mild asthmatics patients was supplemented for three weeks varying doses two seed (borage oil [ Borago officinalis , BO] echium Echium...
Abstract The Notch signaling pathway governs many distinct cellular processes by regulating transcriptional programs. response initiated is highly cell context dependent, indicating that multiple factors influence target gene selection and activity. However, the mechanism which drives transcription not well understood. Herein, we identify characterize a novel Notch-interacting protein, activation complex kinase (NACK), acts as coactivator. We show NACK associates with on DNA, mediates...
Above-knee (AK) amputation substantially increases the metabolic cost of ambulation. Although biomechanical mechanisms contributing to increase have not been well studied, it has assumed that altered center-of-mass (COM) kinematics and increased mechanical work account for adverse effect on oxygen consumption. To understand better relationship between cost, 8 normal subjects traumatic AK amputees were studied during overground Using segmental energy inverse dynamics analyses, trunk COM...
Notch transmembrane receptors direct essential cellular processes, such as proliferation and differentiation, through cell-to-cell interactions. Inappropriate release of the intracellular domain (N(ICD)) from plasma membrane results in accumulation deregulated nuclear N(ICD) that has been linked to human cancers, notably T-cell acute lymphoblastic leukemia (T-ALL). Nuclear forms a transcriptional activation complex by interacting with coactivator protein Mastermind-like 1 DNA binding CSL...
The metabolic costs of above-knee amputee ambulation are significantly greater than normal. role prosthetic mass and distribution on the walking has received limited study. eight unilateral traumatic amputees were therefore studied under varying conditions. All subjects active young with a common prescription, which included total contact ischial containment, suction suspension socket graphlite knee assembly hydraulic unit, Seattle Light Foot (Model Instrument Development, Seattle, WA)....
It is well established that Notch functions as a transcriptional activator through the formation of ternary complex comprises Notch, Maml, and CSL. This then serves to recruit additional cofactors link higher order complexes. The mechanistic details these events remain unclear. report reveals can direct repressor terminate gene expression select target genes. Herein, it demonstrated p19Arf Klf4 are transcriptionally repressed in Notch-dependent manner. Furthermore, results indicate recruits...
Introduction Hypersensitivity reactions (HSR) are a known adverse effect of paclitaxel, occurring in approximately 10% patients, typically during the first or second infusion medication. Corticosteroids, histamine-1 and histamine-2 receptor antagonists given prior to paclitaxel infusions reduce incidence HSR. There limited data that suggest administration cetirizine platinum as secondary prophylaxis may HSR rates. Methods The objective this study was assess impact novel hypersensitivity...
364 Background: Paclitaxel is a commonly used chemotherapy agent effective in various malignancies. It known to cause serious and potentially life-threatening hypersensitivity reactions (HRs). Pre-medication protocols have been employed, however approximately 10% of patients will still experience these (1). On an internal review at the University Louisville, Brown Cancer Center (UofL, BCC) there has considerable increase incidence paclitaxel HRs from 4.2% March 2020 - 2021 14.8% April 2022....
Aging is characterized by an increase in inflammation and immune senescence, which occurs conjunction with changes circulating levels of polyunsaturated fatty acids (PUFA) such as arachidonic acid (AA). Caloric restriction (CR) has been shown to reduce lifespan aged animals. The objective this study was determine the influence aging CR on PUFA levels. Age accompanied a marked AA humans rats. To understand relationship between acids, rats were placed ad libitum (AL) or diets serum determined...
<div>Abstract<p>In many cancers, aberrant Notch activity has been demonstrated to play a role in the initiation and maintenance of neoplastic phenotype cancer stem cells, which may allude its additional involvement metastasis resistance therapy. Therefore, is an exceedingly attractive therapeutic target cancer, but full range potential targets within pathway underexplored. To date, there are no small-molecule inhibitors that directly intracellular or assembly transcriptional...
<div>Abstract<p>In many cancers, aberrant Notch activity has been demonstrated to play a role in the initiation and maintenance of neoplastic phenotype cancer stem cells, which may allude its additional involvement metastasis resistance therapy. Therefore, is an exceedingly attractive therapeutic target cancer, but full range potential targets within pathway underexplored. To date, there are no small-molecule inhibitors that directly intracellular or assembly transcriptional...
<p>Explanation of experimental details for additional methods.</p>
<p>IMR-1 treatment does not induce weight loss in treated mice.</p>
<p>IMR-1 inhibits tumor growth in OE19 xenograft tumor.</p>
<p>Description of the contents supplementary figures 1, 2 and 3.</p>
<p>Primary screen of CADD-derived compounds.</p>
<p>Figure S1 EAC has ligand dependent activation of Notch. Figure S2 Activations Notch were elevated in esophageal adenocarcinoma cell lines. S3 Activation signaling promotes proliferation cells. S4 derived tumor spheres display characteristics cancer stem Table Active NOTCH is associated with poor prognosis EAC.</p>