HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Garcia, J. G. N. Search for Related Content PubMed Articles by Garcia, J. G. N.

Introduction

University of Chicago, Chicago, Illinois

Acute and chronic pulmonary disorders account for a major component of health care expenditures, increased morbidity, and shortened patient survival in the United States and worldwide. Even though the study of the molecular basis of complex lung disorders is a meritorious goal, until recently, this took place on a gene-by-gene basis—that is, with the study of individual genes. The disconnect with this approach, however, is the realization that alterations in organ function produced by disease processes require carefully orchestrated spatial and temporal expression of tens to hundreds of genes. Clearly, new, far-reaching exploratory technologies are critically necessary to alter the sobering clinical statistics by providing new insights into lung pathobiology.

Fortunately, the completion of the Human Genome Project has provided these technologies, enabling rapid, high-throughput genotyping and ushering in the dawn of genomic medicine. There is now ready access to the complete genome sequences of more than 50 prokaryotes; eukaryotic model organisms; and mouse, rat, and dog genome sequences. Large-scale, high-throughput gene expression profiling has sparked efforts to identify specific expression patterns that may aid diagnosis and prognostication, guide therapy, and contribute to our overall understanding of human disease. The ability to monitor the steady-state expression of thousands of genes in a single experiment has literally revolutionized our ability to visualize the cellular environment as a whole.

Knowing the sequence of an organism's genome, whether human or fruit fly, however, is only the first step in developing a thorough understanding of its biology. Despite this genomic information and an explosion in information relating to disease-specific pathogenesis, the ability to identify appropriate diagnostic and therapeutic targets remains limited. New genomic techniques, including the identification and establishment of single nucleotide polymorphisms, new methods of characterizing quantitative trait loci, identification of new pathways of cell function/regulation, new analysis of mechanisms of transcriptional and post-transcriptional regulation, protein–protein interactions, and cross-talk between signaling cascades, as well as parallel developments in computational analysis have now become the conceptual framework for translational biomedical research. While this underscores the fact that genomic data and techniques are increasingly applied to the study of biological problems, significant genomic challenges remain, including the following: characterization of gene products, understanding their role in physiology, and delineating their association with human diseases. Given the expense involved in some genomic studies, it remains unclear as to how many samples, which platforms, what time points, and, more pragmatically, which experimental models are the most appropriate to study. Another real challenge facing the current generation of translational researchers is how best to analyze the unprecedented quantities of data generated by these approaches: that is, how to collect and integrate these data and how to use the available tools and techniques to produce a comprehensive understanding of fundamental biological processes both in health and in disease. Nevertheless, it is clear that characterization of genes abnormally expressed in diseased tissues provides the promise for the identification of novel genes that serve as biomarkers, diagnostic markers, prognostic indicators, and targets for therapeutic intervention.

In this issue of the Proceedings, a cast of highly qualified experts in clinical pulmonary medicine, comparative genomics, microarray platforms, genetic epidemiology, statistical genetics, proteomics, and bioinformatics addresses the promise of molecular/genomic medicine as it applies to pulmonary pathobiology. These state-of-the-art discussions present current approaches by which to investigate the myriad potential factors that drive susceptibility and severity of enigmatic and complex acute and chronic pulmonary disorders. For example, several articles highlight the utility of combining advanced bioinformatic techniques with multispecies gene expression profiling as a way to broaden our net for identifying lung-related genes, an approach ideal to complement more traditional, hypothesis-based testing of candidate genes. Another relevant—and as yet unsolved—challenge addressed by our team of experts is the determination of exactly which environmental and genetic factors are relevant within well-phenotyped populations of patients with complex lung disease, because the science continues to be constrained by incomplete understanding of gene–environment interactions. We have also attempted to cover available genetic/genomic/proteomic knowledge across a spectrum of lung disease and selected conditions, not only because of their imposing morbidity and mortality and the need for improved therapeutic options but to elucidate thematic associations across diverse ontologies, such as innate immunity, coagulation, angiogenesis, and vascular development.

The genomic era continues to provide the promise of translating basic genetics, biochemistry, and cell biology into pathophysiologic cascades that permit precise intervention targeting. In the end, what becomes ever increasingly clear is that the genomic era, in its truest sense, represents the powerful capacity of genomics to bring clinicians, clinician-scientists, biomedical biologists, and genetic epidemiologists together for a common goal in a way not previously imagined. For pulmonary scientists, the quest remains to understand the genetic basis of highly complex lung pathophysiology as well as the role of genes in normal human lung development and physiology. With the dawn of the genomic era, the elucidation of the molecular basis of complex lung disorders and the development of highly individualized therapies, appropriate to that patient and with little risk and high likelihood of success, remain a lofty but achievable goal.

FOOTNOTES

Conflict of Interest Statement: J.G.N.G. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Garcia, J. G. N. Search for Related Content PubMed Articles by Garcia, J. G. N.