This proposal establishes a five year plan for Dr. Ronald Sanders Jr. to develop the skills and experience needed to be a successful clinician/scientist in the field of Pediatric Critical Care. Currently, Dr. Sanders has completed 3 years of a clinical fellowship in pediatric critical care. Dr. Sanders has a strong interest in respiratory physiology and worked under the auspices of Dr. Mark Heulitt over 3 years investigating imposed work of breathing with mechanical ventilation. In addition, he earned a masters degree in the department of physiology and biophysics during the last two years of his fellowship. He studied an in vitro wound healing model that could quantify cell migration, spreading and proliferation using an immortalized respiratory epithelial cell line in the lab of Dr. Richard Kurten. After his fellowship, he spent a year in the lab of Dr. Billie Moat-Staats practicing techniques in RT-PCR, molecular cloning, plasmid splicing and in situ hybridization using rodent respiratory lung cells/tissue. Dr. Sanders immediate goal is to broaden his research skills through a combination of a carefully structured didactic teaching program and completion of a research project in the laboratory of his mentor. Dr. Sanders long-term goal is to become an independent investigator capable of combining the discipline of stem cell biology with issues of respiratory pathology in clinical critical care. Dr. Sanders' research project is based on the hypothesis that the adult hematopoietic stem cell serves as a progenitor for pulmonary angiogenesis after lung injury. This hypothesis is based on the observation in the Scott laboratory of hemangioblastic activity from adult hematopoietic stem cells after a retinal ischemic injury. In addition, Dr. Sanders has observed GFP+ signals in the lung tissue of mice from the retinal ischemic model that were transplanted with GFP+ bone marrow. The Scott lab has refined the methodology of stem cell transplantation in the murine model. Dr. Scott's laboratory provides an excellent environment for Dr. Sanders to carry out this proposal. A research advisory committee that meets the NIH requirements has been arranged that will assist Dr. Sanders in achieving his goals. In this rich and supportive environment, Dr. Sanders will gain the experience necessary to contribute to the understanding of the early cellular and in vivo events in angiogenesis related to acute lung injury.
