PROJECT SUMMARY Candidate: Dr. Jaitovich academic training, research experience and intense drive place him in an excellent position for a successful career as an independent physician/scientist. Dr. Jaitovich is an Argentinean immigrant who has developed extensive expertise in the field of protein turnover and degradation, and has worked in collaboration with Nobel Prize- winner Aaron Ciechanover, which reflects his remarkable standard of training in that field. In addition, he has been recruited as Assistant Professor of Pulmonary and Critical Care Medicine at Albany Medical College based on feedback he received upon submission of his NRSA award. At that time, and due to his strong interest in skeletal muscle atrophy in the context of pulmonary diseases, he was recommended to find an institution with higher expertise in muscle biology. He has recently established collaborations with two world experts in animal models of emphysema: Drs. Jack Elias and Jeanine D’Armiento, who will provide him the opportunity to test his hypotheses in complementary transgenic animals with previously developed lung disease. Dr. Jaitovich intends to pursue a career in academic medicine with a strong commitment to innovative basic and translational research. He has used his fellowship training to gain expertise in cell biology and in murine models of disease. Supported by this award, he will establish a novel niche within the area of muscle atrophy in the context of advanced pulmonary disease. Training supported by this K01 award will allow him to pursue his career as an independent investigator. Environment Mentorship: The Division of Pulmonary and Critical Care Medicine and the Center for Cardiovascular Sciences at the Albany Medical College are committed to fostering the academic careers of outstanding junior faculty like Dr. Jaitovich. Drs. Harold Singer, Yong-Xiao Wang and Dale Tang are well-funded, established investigators with a long track record of training. Their laboratories have the tools and resources required to complete the proposed studies, which have been specifically crafted to develop a novel and innovative research program independent from their own, and which will facilitate Dr. Jaitovich career. In addition, Dr. Jaitovich will receive full collaboration from Dr. Jacob Sznajder (Northwestern University), who is an expert in CO2-mediated cell signaling; Dr. Jack Elias (Brown University), who is an expert in animal models of emphysema/COPD; Dr. Jeanine D’Armiento (Columbia University), who is also an expert in animal models of emphysema and has described one of the first transgenic animals of that kind (lung MMP1+/- expression); Dr. Gustavo Nader (Penn State University), who has advanced expertise in regulation of anabolism in skeletal muscle; Dr. Esther Barreiro (Universitat Pompeu Fabra, Barcelona), a leading scientist in the field of COPD- associated muscle atrophy; and Dr. Jiang Qian (Albany Medical Center), who is the head of the neuromuscular...