PROJECT SUMMARY
Project Summary: This proposal describes a five-year training program that will ultimately develop Dr. Kara
Mould into an independent academic basic science investigator. Her long-term career goal is to advance the
field of macrophage biology through the elucidation of targets for lung repair and the treatment of patients with
the acute respiratory distress syndrome or inflammatory lung diseases. During this K08 Award, Dr. Mould will
gain specific career development training and mentorship closely aligned with an innovative research plan. She
proposes to study the affect of arginine metabolism on alveolar macrophage programming in models of acute
lung injury. Given its applicability to multiple pulmonary disorders and potential applicability to repair of injury in
other organs, this work is directly relevant to the NHLBI.
Candidate: Dr. Mould is a board-certified Pulmonary and Critical Care Medicine physician at the University of
Colorado School of Medicine. She is in the final year of fellowship training, having elected to complete an
optional year of dedicated research. Her previous record of academic excellence, basic science research, and
scientific publications demonstrates a firm commitment to a career as an academic clinician-scientist.
Training: The proposed career development plan augments Dr. Mould's prior mentored research during her
undergraduate, medical, residency, and fellowship training. She proposes to meet her short-term objectives
through an integrated combination of intensive mentoring by internationally renowned experts in macrophage
biology and didactic and hands-on experiences in (i) Immunology, (ii) metabolic programming of immune cells
(iii) bioinformatics, (iv) scientific writing and presentation, and (v) laboratory leadership.
Mentors/Environment: Dr. Mould has established close working relationships with highly experienced
mentors and collaborators who contribute expertise in macrophage and lung biology (Drs. Henson and
Janssen), metabolomics (Dr. D'Alessandro), bioinformatics (Dr. Fingerlin), human lung and epithelial biology
(Dr. Mason), endothelial biology (Dr. Petrache), and career development of clinician-scientists (Drs. Douglas,
Eickelberg, and Voelker.) The proposed activities will be based at National Jewish Health with support from the
University of Colorado, both renowned respiratory medical centers and world-class research institutions.
Research Project: The primary objective of this proposal is to identify the mechanism by which alveolar
macrophages are programmed to resolve inflammation and promote repair of the injured lung. Specifically, our
study will test the hypothesis that the metabolic enzyme, arginase 1, is a critical checkpoint for both
inflammatory and reparative programming of alveolar macrophages. This will be tested using a well-
established murine model of lung injury and primary cells isolated from diseased human lungs or non-diseased
controls. In doing so, the specific contribution of arginine metabolism to macrophage programming and
pathways that regulate recovery from inflammatory lung diseases will be elucidated.