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Ceramide-Rich Platforms Functionalize Gemcitabine Uptake
Our data indicate that in select settings activation of acid sphingomyelinase (ASMase)/ceramide signaling in tumor endothelial cells by radiation and certain chemotherapies synergi...
Chemotherapy-induced vascular cognitive impairment: role of endothelial senescence
Project Summary Many long-term survivors of cancer experience progressive chemotherapy-induced cognitive impairment (CICI, commonly referred to as "chemobrain"). Importan...
Normalizing aberrant metabolism in ovarian cancer by a unique drug delivery system
Gene silencing using small interfering RNA (siRNA) is a viable therapeutic approach but, limited in translation due to lack of effective delivery systems. Developing effective and...
A versatile "pan-spike-in" internal reference genome methodology for quantitative ChIP-seq normalization
Project summary: ChIP-seq has enabled the mapping of genomic occupancy of many chromatin factors and epigenetic histone modifications, linked to normal growth and development and t...
Applying and advancing modern approaches for studying the joint impacts of environmental chemicals on pregnancy outcomes
Preterm birth is a significant public health challenge due to increasing rates over time, as well as serious consequences for infant mortality, childhood morbidity, and economic co...
Assessing the Influence of the Human Lipidome on Risk of Diabetes in a Minority Population
PROJECT SUMMARY Type 2 diabetes is a major public health concern. Diabetes currently affects 25.8 million people in the US alone and 90-95% of all cases are type 2. There are many...
Defining the role of Mst1/Mst2 in regulating metabolic alterations in Ras driven NSCLC
PROJECT SUMMARY/ABSTRACT Non-small cell lung cancer (NSCLC) remains the most commonly diagnosed malignancy and leading cause of cancer related deaths worldwide; yet there is a fund...
DNA-based Immune Phenotyping in HNSCC for Biomarkers of Response to Immunotherapy
PROJECT SUMMARY/ABSTRACT Head and Neck Squamous Cell Carcinomas (HNSCCs) are devastating upper airway tumors that are associated with an immunosuppressive network impacting the tum...
Therapeutic Targeting Mitochondrial C1 Metabolism
ABSTRACT Metabolic reprogramming is an important hallmark of cancer. Of the altered metabolic pathways associated with malignancy, one-carbon (C1) metabolism is particularly notabl...
DEHART: Dose-Escalated Hypofractionated Adaptive Radiation Therapy for Head and Neck Cancers
Abstract Locoregional failure remains the principal mode of mortality in head and neck squamous cell carcinomas (HNSCCs) treated with conventional chemoradiation therapy over 7 wee...
Role of MIF and CD74 in the pathogenesis of emphysema
PROJECT SUMMARY Emphysema is a common pathologic manifestation of Chronic Obstructive Pulmonary Disease (COPD), the fourth leading cause of death in the United States. The most imp...
Discovery and development of artificial nucleic acid ligands to probe cellular interactions
Discovery and development of artificial nucleic acid ligands to probe cellular interactions The regulation followed by measurement of cellular events, such as intercellular communi...
Understanding and Targeting Tiam1 in Cancer
Project Summary: Understanding the detailed mechanisms that underlie proliferative signal transduction pathways is of critical importance for developing strategies for diagnosis an...
2/3 Genomics of Schizophrenia in the South African Xhosa
PROJECT DESCRIPTION The goal of this international collaborative project, in response to PAR-20-027, is to characterize the genetic architecture of schizophrenia in the Xhosa popul...
mTOR-Mediated Desaturation of Fatty Acids in Hepatic Insulin Resistance.
Discharged members of the US Armed Services are at an increased risk of metabolic disease which is exemplified by the prevalence of type 2 diabetes mellitus (T2DM) affecting an est...
COVID-19: Characterizing trained immune responses to COVID-19
In late 2019, a novel human betacoronavirus emerged in Wuhan, China and subsequently led to pandemic spread. Designated Severe Acute Respiratory Virus 2 (SARS CoV-2), this virus ha...
CMA: Network plasticity in acquired epileptogenesis
Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and a major source of disability in the veteran population as it is frequently caused by war-time head in...
Pathologic Signaling Pathways in AML Cells
Abstract: Acute myeloid leukemia (AML) is a serious blood cancer that affects United States Veterans and other individuals. Multiple studies have demonstrated that active signaling...
Preoptic/Hypothalamic Mechanisms of Sleep-Wake Regulation
ABSTRACT Chronic sleep disturbance is a frequent and challenging problem of human aging. In the US an estimated 39.6 million people including 8.5 million Veterans are aged 65 or ol...
A role and regulation of glucose responsive lipolysis in pancreatic beta cells
T2D is a major health problem for US veterans that imposes significant physical, financial, and emotional tolls. Thus, there is a strong and urgent need for an effective and widely...