The candidate's goal is to develop a strong and independent program in vascular biology. In particular, he intends to apply a background in molecular mechanisms of gene regulation toward understanding certain fundamental processes involved in cardiovascular disease. The present proposal is focused on understanding how vascular smooth muscle cells modulate from a quiescent, contractile phenotype to a proliferative phenotype during vascular injury, as well as to study the mechanisms involved in induction to a contractile phenotype. In particular, the hypothesis that cellular growth-arrest is intimately associated with modulation to a contractile phenotype, will be tested. Furthermore, it is proposed that understanding the developmental regulation of smooth muscle cells may provide important insights into phenotypic modulation of smooth muscle cells during vascular injury. Experiments are described to isolate and characterize genes expressed in defined smooth muscle cell phenotype. Understanding the function and regulation of such genes may provide a better understanding of cardiovascular disease. Dr. Liau is an independent scientist in the Laboratory of Molecular Biology and is one of five senior investigators. He has approximately 500 sq. ft. of well equipped lab space with an adjacent office. The major interest of the investigators in the Laboratory of Molecular Biology are in growth factors with a particular emphasis on their role in modulating endothelial and smooth muscle cell biology . The natural overlap in research interests allows a great deal of interdepartmental interactions. iN addition, the biomedical research and development division is composed of eight additional departments, plus support facilities. Four of these departments are basic research groups in which projects are investigator-initiated and funded largely by outside granting agencies. The other departments are developmental groups involved projects deemed important to, and funded largely, by the American Red Cross. The research support services include a well-staffed computer center, a library which contains over 150 journal and periodical titles, an art and photography department, and instrument shop and a fully accredited vivarium. Dr. Liau will also have access to Core Facilities which can provide peptide and oligonucleotide synthesis, protein sequencing and antibody production. The candidate's position (Scientist I) is equivalent to an assistant professor level. At present, he has considerable administrative duties associated with Red Cross activity, as well as internal administration. The RCDA will allow Dr. Liau to devote essentially 100% of his time to research and research-related activities. It is expected that Dr. Liau will establish a record of outstanding contributions to his field, upon which he will be promoted to a senior scientist position. The budget support for Dr. Liau will continue at current levels for the period of the RCDA. In summary, the environment and resources to facilitate the development of Dr. Liau's career are excellent and the organization fully recognizes its interest in promoting that goal.