Discovery of direct antimicrobial properties of SP-A and SP-Dĥ. Development of serum SP-A and VEGF-D as biomarkers in interstitialĤ. Characterization of the structure and function relationship of surfactant proteins A (SP-A) and D (SP-D)ģ. Solution of the crystal structure of SP-A (with Barbara Seaton)Ģ. In pulmonary disease and operates a CCTST-funded bronchoscopy core for the collection of lung samples.ġ. McCormack and Trapnell have also developed a collaborative UC/CCHMC program called the Translational Pulmonary Science Center, which organizes the resources necessary for translational research LAM who have normal lung function (the MILED trial). Pulmonary alveolar proteinosis, developing CT scanning as a biomarker of progression for alpha-1 antitrypsin deficiency, developing a longitudinal registry for LAM (MIDAS), and conducting a MILES-like trial of sirolimus in asymptomatic patients with ![]() Other past and present Cincinnati-based RLDC projects have included developing a pathologic classification system for the pediatric interstitial lung diseases, developing diagnostic tests for Of LAM patients in North America are now taking the drug. On the basis of the MILES result, the FDA approved sirolimus for LAM in 2015, and over 40 percent The RLDC conducted the MILES trial for LAM, which demonstrated that sirolimus is an effective treatment. We intend to conduct a trial in PAM patients through the NIH Rare Lung Disease Consortium, a network of 55 rare lung disease clinics located around the world, with Cincinnati as the hub, with co-investigatorsīruce Trapnell, MD, and Frank McCormack, MD. Phosphate transporters in the alveolar epithelium. Our lab is actively trying to understand the mechanism of stone clearance due to phosphate restriction, focusing on the effect of phosphate hormone mediators such as VitD3 and FGF-23 on expression of alternative We have also found that a low phosphate diet reduces the stone burden in the lung, suggesting that a simple dietary intervention (perhaps together with a phosphate binder)Ĭould be developed as a treatment. ![]() ![]() We found that stones isolated from the lungs of the PAM mice readily dissolve in calcium chelators such as EGTA and EDTA, suggesting therapeutic chelation lavage as a treatment approach Īn idea we intend to test in monkeys and bring to the bedside if proven safe. We contacted a dozen PAM patients around the world to obtain blood, and found that MCP-1 and SP-D are also elevated in the serum of patients, and are now developing them as promisingīiomarkers for disease progression and response to therapy. PAM mouse serum, suggestive of lung injury and barrier dysfunction. We also found that the very large alveolar protein, surfactant protein D (SP-D), was elevated in The cytokine MCP-1 is elevated in the lungs of the PAM animals, and also appears in their serum. The animals develop diffuse pulmonary alveolar microliths, which produce hyperdense infiltrates on radiographsĪnd C/T scans that are easily measured and quantified. As an example, we developed the PAM mouse modelīy deleting the phosphate transporter, Npt2b, from the alveolar epithelium, as mutations in that protein are known to cause the disease in humans. We use animal models to develop biomarkers and strategies for trials, and try to focus on experimental plans that have a human trial on the horizon. In influenza, mycobacterial and bacterial infection. Current projects are focused on lymphangioleiomyomatosis (LAM), pulmonary alveolar microlithiasis (PAM) and the role of the alveolar epithelium The McCormack laboratory is interested in genetic interstitial lung diseases and pulmonary innate immunity. Many of our laboratory directions have been inspired by patients we have met, which gives our work purpose and meaning, and motivates us to ask questions that matter. To favorably impact human health in a short time frame. ![]() Our goal is to develop new biomarkers and therapies with the potential Our group is broadly interested in translational research of rare lung diseases, which allows us to approach disease pathogenesis from the vantage point of a known molecular defect. McCormack Laboratory - Translational and Rare Lung Disease Laboratory
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