The applicant describes a five year program leading to independent translational research related to pulmonary and critical care medicine. Although trained as a neuroscientist, the investigator is motivated by clinical experience to propose a career dedicated to the development of molecular diagnostic and targeted therapeutic approaches to medicine, in particular to lung cancer and critical illness. Practical skills in functional genomics, proteomics, molecular biology, biostatistics, and machine learning will be fostered in the laboratory of Dr. Todd Golub, himself an accomplished clinical scientist with a vital independent research program. Director of Cancer Genomics at the Whitehead Institute Center for Genome Research, Dr. Golub is a pioneer and internationally recognized leader in the application of genomics approaches to cancer biology, especially classification and prognosis. This immersion will be complemented by formal instruction in genomics and computational biology, and reinforced by active advising from a team of domain experts. The proposed research plan starts from the tenet that delayed or inaccurate diagnoses can be lethal. Most lung cancer patients present with advanced disease, when the prognosis is grave; many of the critically ill can be given no better than phenomenological descriptions of their disease. The Human Genome Project and other developments in biology and technology have advanced unbiased, whole-genome discovery efforts for improved markers of disease. The principal investigator will undertake such an effort, by 1) creating datasets by mass spectrometry from serum samples of lung cancer patients and controls; 2) defining signatures of disease using machine learning approaches; and 3) identifying proteins and peptides comprising the diagnostic signatures. While the investigator hopes to develop functional lung cancer biomarkers, the methodologies are intended to be applicable throughout medicine. The combined resources of the Massachusetts General Hospital, the Dana Farber Cancer Institute, and the Whitehead Institute will be available to the applicant. These rich environments will promote the success of the serum biomarker discovery project, and the larger cultivation of the investigator towards a goal of independence and productivity in academic medicine.