Project Summary Candidate Katharine Black, MD is a faculty member of the Division of Pulmonary and Critical Care Medicine (DPCCM) at Massachusetts General Hospital (MGH), and an Instructor in Medicine on the tenure track at Harvard Medical School (HMS). She came to MGH with a strong interest and research background in interstitial lung disease, and is now working in the laboratory of Dr. Andrew Tager at the MGH Center for Inflammation and Inflammatory Diseases (CIID). Dr. Tager is a recognized leader in basic mechanisms underlying fibroblast activation, and in his laboratory she has established expertise in the evaluation of mediators of fibroblast activation. She is now focusing on alveolar epithelial cell (AEC) injury as a source of these fibroblast-activating mediators, and on profiling AEC responses to injury in animal and human cell culture models of fibrosis. Her long-term career goal is to determine the pathways that trigger and exacerbate pulmonary fibrosis, and to move the discoveries of basic biology closer to patient care, bringing the basic science and the clinical problem of interstitial lung disease together. The short-term goals of this grant are to delineate the pro-fibrotic AEC responses to endoplasmic reticulum (ER) stress pathways in vitro and in vivo. The experiments, training, and mentoring plans outlined in the proposal will position Dr. Black extremely well for her first R01 application, and for an independent career as a physician-scientist. Mentorship, Training Activities and Environment The training program described in this proposal is located primarily in the DPCCM and the CIID, both well- established environments for training high successful physician-scientists. Under the mentorship of Dr. Tager, Dr. Black has developed a research and training plan that will equip her with the necessary knowledge and experimental techniques required to move successfully from a mentored to an independent position. This K08 award will provide additional training in epithelial cell biology and in analysis of large sequencing data sets, and will expand the human subject work she began in establishing a tissue bank of lung explants from patients with pulmonary fibrosis. To accomplish her research and career goals, Dr. Black will make use of Dr. Tager’s laboratory’s expertise in modeling pulmonary fibrosis. She will additionally obtain training in epithelial cell biology and in more advanced sequencing analysis through collaboration and consultation with a carefully assembled team of experts, including those who form her Training Advisory Committee. Drs. Jay Rajagopal, Timothy Blackwell, and Benjamin Humphreys will share their expertise in lung epithelial cell development and repair, pathways of ER stress in pulmonary fibrosis and human tissue-based research, and the use of cell-specific translational profiling in analysis of fibrotic injury, respectively. In addition, she will receive formal training in epithelial cell development, cellul...