The healthy human respiratory tract is lined with a pseudostratified epithelia composed of ∼80% ciliated cells and ∼20% goblet cells. These cells produce and are bathed by a layer of airway surface liquid (ASL), which plays a critical role in lung defense by helping to maintain the sterility of the lu ...
Cystic fibrosis is characterized by excessive pulmonary inflammation, which presents early in life and becomes self-sustaining, eventually leading to the destruction of the lung. Treating inflammation is one of the most pressing needs in CF therapy and has been shown to slow lung function ...
Cystic fibrosis (CF) is a lethal genetic disorder, characterized by both clinical and genetic complexities, and arises as a result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The gene encodes a Cl− channel belonging to the ABC (ATP Binding Cassette) ...
CFTR functions as a chloride channel at the apical membrane of airway, gastrointestinal, and other epithelial cells. Immunofluorescence microscopy is commonly used to assess the subcellular localization and relative abundance of CFTR. Visualization of heterologously overe ...
Mutation of the CFTR chloride channel was identified as the genetic basis of cystic fibrosis over 20 years ago; however, correlation of the pathophysiological changes occurring in CF lung disease with the mutation of a chloride channel is ongoing. The failure of innate lung defense in CF, and the su ...
One of the main functions of the airway mucosa is to maintain a mechanical barrier at the air–surface interface and to protect the respiratory tract from external injuries. Differentiation of human airway epithelial cells (hAECs) to polarized airway mucosa can be reproduced in vitro by cult ...
Bicarbonate serves many functions in our body. It is the predominant buffer maintaining a physiological pH in the blood and within our cells. It is also essential for proper digestion of nutrients and solubilization of complex protein mixtures, such as digestive enzymes and mucins, in epithe ...
MicroRNAs (miRNAs) are small, single-stranded RNA molecules encoded by genes that are transcribed from DNA but not translated into protein (noncoding RNA). The ability of miRNA to regulate the expression of, as yet, an unknown quantity of targets has recently become an area of huge interest to re ...
New technologies allow for genome-scale measurement of DNA methylation. In an effort to increase the clinical utility of DNA methylation as a biomarker, we have adapted a commercial bisulfite epigenotyping assay for genome-wide methylation profiling in archival formalin-fixed p ...
The introduction of microarray technology, which is a multiplexed hybridization-based process, allows simultaneous analysis of a large number of nucleic acid transcripts. This massively parallel analysis of a cellular genome will become essential for guiding disease diagnos ...
The Science of Genomes: Only within the past few decades have scientists progressed from the analysis of a single or a small number of genes at once to the investigation of thousands of genes, going from the study of the units of inheritance to the investigation of the whole genome of an organism. The science ...
The future success of translational research is critically dependent on the procurement and availability of high-quality tissue specimens linked to accurate histopathologic and clinical information about the individual banked specimen. The international community has a ...
Despite the tremendous perceived value, and the predicted high abundance, of disease-associated tissue biomarkers, the number of biomarkers that have been validated for routine clinical use is very low. The major roadblock has been the sample-to-sample variability and perishabil ...
Modern ethical codes in medicine were developed following World War II to provide respect for persons, beneficence, and justice in clinical research. Clinical trial medicine involves greater scrutiny than most research activities. In every instance, clinical trials have institu ...
The accelerating science of molecular profiling has necessitated a rapid evolution in clinical trial design. Traditional clinical research begins with Phase I studies to characterize dose-limiting toxicities and defines maximally tolerated doses of drugs in small numbers of pa ...
Molecular profiling, which is the application of molecular diagnostics technology to tissue and blood �specimens, is an integral element in the new era of molecular medicine and individualized therapy. Molecular diagnostics is a fertile ground for small business development beca ...
This chapter describes the basic categories for regulatory approval to sell/market a molecular profiling technology. The US Food and Drug Administration regulates and provides guidance, for marketing in vitro diagnostic devices (IVD). Three different paths currently exist for o ...
Patents are designed to protect and encourage creativity and innovation. Patenting a biomedical discovery can be a requirement before a pharmaceutical company or biotech entity will invest in the lengthy and costly clinical testing necessary to achieve patient benefit. Although sc ...
All investigators face the same challenge – the highly competitive nature of the grant review process. Innovation alone is not enough to ensure grant supported funding. Applied clinical research requires a diverse collaborative team of investigators with specialized skills, a supp ...
Despite an increased investment in research and development, there has been a steady decline in the number of drugs brought to market over the past 40 years. The tools of personalized medicine are refining diseases into molecular categories, and future therapeutics may be dictated by a patient ...

