2006 Dickinson W. Richards Memorial Lecture—Wading in the Genomic Pool for Insights Into Lung Vascular Pathobiology
The completion of the Human Genome Project enabled rapid, high-throughput genotyping and gene expression profiling, thereby ushering in the era of genomic medicine. The promise of molecular/ genomic medicine is that we may rapidly ascertain a patient’s genetic and molecular profile and thus target highly individualized therapies appropriate to that patient with little risk and high likelihood of success. In this lecture, we present currently available approaches to investigate potential genetic susceptibility factors that have led to the identification of several genes that impact susceptibility, protection, or severity in enigmatic and complex pulmonary syndromes such as acute lung injury (ALI). We highlight the utility of combining advanced bioinformatic techniques with multispecies gene expression profiling as a way to broaden our net for ALI-related genes. This genome-wise approach is the ideal complement to more traditional, hypothesis-based testing of candidate genes. We anticipate that the genome-wide approach will fuel additional analysis of new candidates while allowing for a wide-angle view of key biological processes such as inflammation, coagulation, and cell proliferation. It remains challenging to determine exactly which environmental and genetic factors are relevant within well-phenotyped populations of patients with complex lung disease (such as ALI/ARDS), and we continue to be constrained by our incomplete current understanding of how various factors interact. Nevertheless, with the dawn of the genomic era, the study of lung pathobiology and the elucidation of the molecular basis of complex lung disorders remains a lofty but achievable goal.