David W. Brown

Learn More
MicroRNAs (miRNAs) are regulatory RNAs found in multicellular eukaryotes, including humans, where they are implicated in cancer. The let-7 miRNA times seam cell terminal differentiation in C. elegans. Here we show that the let-7 family negatively regulates let-60/RAS. Loss of let-60/RAS suppresses let-7, and the let-60/RAS 3'UTR contains multiple let-7(More)
Cancer stem cells (CSCs), or tumor-initiating cells, are involved in tumor progression and metastasis. MicroRNAs (miRNAs) regulate both normal stem cells and CSCs, and dysregulation of miRNAs has been implicated in tumorigenesis. CSCs in many tumors--including cancers of the breast, pancreas, head and neck, colon, small intestine, liver, stomach, bladder(More)
MicroRNAs play important roles in animal development, cell differentiation, and metabolism and have been implicated in human cancer. The let-7 microRNA controls the timing of cell cycle exit and terminal differentiation in Caenorhabditis elegans and is poorly expressed or deleted in human lung tumors. Here, we show that let-7 is highly expressed in normal(More)
MicroRNAs have essential functional roles in brain development and neuronal specification but their roles in neurodegenerative diseases such as Alzheimer's disease (AD) is unknown. Using a sensitive qRT-PCR platform we identified regional and stage-specific deregulation of miRNA expression in AD patient brains. We used experimental validation in addition to(More)
Tumor suppressor microRNAs (miRNA) provide a new opportunity to treat cancer. This approach, "miRNA replacement therapy," is based on the concept that the reintroduction of miRNAs depleted in cancer cells reactivates cellular pathways that drive a therapeutic response. Here, we describe the development of a therapeutic formulation using chemically(More)
Oxidative stress may play a role in the pathophysiology of diabetes and cardiovascular disease, but little is known about antioxidant status among individuals with the metabolic syndrome who are at high risk for developing these conditions. Using data from the Third National Health and Nutrition Examination Survey (1988-1994), we compared circulating(More)
BACKGROUND Although the benefits of regular physical activity on morbidity and mortality are established, relationships between recommended levels of physical activity and health-related quality of life (HRQOL) have not been described. The authors examined whether recommended levels of physical activity were associated with better HRQOL and perceived health(More)
The decrease in plasticity that occurs in the central nervous system during postnatal development is accompanied by the appearance of perineuronal nets (PNNs) around the cell body and dendrites of many classes of neuron. These structures are composed of extracellular matrix molecules, such as chondroitin sulfate proteoglycans (CSPGs), hyaluronan (HA),(More)
MicroRNAs (miRNA), a class of natural RNA-interfering agents, have recently been identified as attractive targets for therapeutic intervention. The rationale for developing miRNA therapeutics is based on the premise that aberrantly expressed miRNAs play key roles in the development of human disease, and that correcting these miRNA deficiencies by either(More)
In the period 1992-2000, the Public Health Laboratory Service Communicable Disease Surveillance Centre collected standardized epidemiologic data on 1,877 general outbreaks of Norovirus (formerly "Norwalk-like virus") infection in England and Wales. Seventy-nine percent of general outbreaks occurred in health-care institutions, i.e., hospitals (40%) and(More)