The Experts below are selected from a list of 17256 Experts worldwide ranked by ideXlab platform
Lisa R. Young - One of the best experts on this subject based on the ideXlab platform.
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Gene-edited MLE-15 Cells as a Model for the Hermansky-Pudlak Syndromes.
American journal of respiratory cell and molecular biology, 2018Co-Authors: Seunghyi Kook, Lisa R. Young, Ping Wang, Shufang Meng, Peter M. Gulleman, Susan H. GuttentagAbstract:Defining the mechanisms of cellular pathogenesis in Rare Lung Diseases such as Hermansky-Pudlak syndrome (HPS) is often complicated by loss of the differentiated phenotype of cultured primary alveolar type 2 (AT2) cells, as well as by a lack of durable cell lines that are faithful to both AT2-cell and Rare Disease phenotypes. We used CRISPR/Cas9 gene editing to generate a series of HPS-specific mutations in the MLE-15 cell line. The resulting MLE-15/HPS cell lines exhibit preservation of AT2 cellular functions, including formation of lamellar body-like organelles, complete processing of surfactant protein B, and known features of HPS specific to each trafficking complex, including loss of protein targeting to lamellar bodies. MLE-15/HPS1 and MLE-15/HPS2 (with a mutation in Ap3β1) express increased macrophage chemotactic protein-1, a well-described mediator of alveolitis in patients with HPS and in mouse models. We show that MLE-15/HPS9 and pallid AT2 cells (with a mutation in Bloc1s6) also express increased macrophage chemotactic protein-1, suggesting that mice and humans with BLOC-1 mutations may also be susceptible to alveolitis. In addition to providing a flexible platform to examine the role of HPS-specific mutations in trafficking AT2 cells, MLE-15/HPS cell lines provide a durable resource for high-throughput screening and studies of cellular pathophysiology that are likely to accelerate progress toward developing novel therapies for this Rare Lung Disease.
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accelerating scientific advancement for pediatric Rare Lung Disease research report from a national institutes of health nhlbi workshop september 3 and 4 2015
Annals of the American Thoracic Society, 2016Co-Authors: Lisa R. Young, Bruce C. Trapnell, Kenneth D. Mandl, Daniel T. Swarr, Jennifer A. Wambach, Carol J. BlaisdellAbstract:Pediatric Rare Lung Disease (PRLD) is a term that refers to a heterogeneous group of Rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify ...
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Accelerating Scientific Advancement for Pediatric Rare Lung Disease Research. Report from a National Institutes of Health–NHLBI Workshop, September 3 and 4, 2015
Annals of the American Thoracic Society, 2016Co-Authors: Lisa R. Young, Bruce C. Trapnell, Kenneth D. Mandl, Daniel T. Swarr, Jennifer A. Wambach, Carol J. BlaisdellAbstract:Pediatric Rare Lung Disease (PRLD) is a term that refers to a heterogeneous group of Rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify ...
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Predictors for clinical trial participation in the Rare Lung Disease lymphangioleiomyomatosis.
Respiratory medicine, 2009Co-Authors: Brent W. Kinder, Lisa R. Young, A.c. Sherman, Jared T. Hagaman, N. Oprescu, S. Byrnes, Francis X. MccormackAbstract:Summary Background Lymphangioleiomyomatosis (LAM) is a Rare, progressive and frequently lethal cystic Lung Disease that almost exclusively affects women and has no proven therapies. An improved understanding of the pathogenesis has identified promising molecular targets for clinical trials. Although barriers, modifiers, and benefits for clinical trial participation in common Diseases such as cancer have been studied, we are unaware of such evaluations concerning Rare Diseases. Methods We performed a survey of a population-based registry of 780 LAM subjects in North America to identify predictors of trial participation. Logistic regression analysis evaluated the association of demographic and clinical features with trial participation. Results 41 of 263 (16%) LAM patient respondents in North America had participated in a clinical trial. Age, Disease duration, lack of any college education, use of oxygen therapy, and presentation without chest pain were associated with trial participation in unadjusted analyses. Multivariate analyses indicate that patient age was the strongest independent predictor for trial participation (OR=2.07, p =0.004 per decade greater of patient age). Common reasons reported against trial participation included not meeting enrollment criteria (44%), drug toxicity (25%), and stable Disease (20%). The most frequent reason reported for trial participation was to help future patients (85%). Conclusions Study entry criteria, drug toxicity, and stability of Disease are barriers to trial enrollment among subjects with LAM. Older LAM patients and those with more advanced Disease are more likely to have participated in clinical trials. Altruism is commonly a motivating factor.
Carol J. Blaisdell - One of the best experts on this subject based on the ideXlab platform.
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accelerating scientific advancement for pediatric Rare Lung Disease research report from a national institutes of health nhlbi workshop september 3 and 4 2015
Annals of the American Thoracic Society, 2016Co-Authors: Lisa R. Young, Bruce C. Trapnell, Kenneth D. Mandl, Daniel T. Swarr, Jennifer A. Wambach, Carol J. BlaisdellAbstract:Pediatric Rare Lung Disease (PRLD) is a term that refers to a heterogeneous group of Rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify ...
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Accelerating Scientific Advancement for Pediatric Rare Lung Disease Research. Report from a National Institutes of Health–NHLBI Workshop, September 3 and 4, 2015
Annals of the American Thoracic Society, 2016Co-Authors: Lisa R. Young, Bruce C. Trapnell, Kenneth D. Mandl, Daniel T. Swarr, Jennifer A. Wambach, Carol J. BlaisdellAbstract:Pediatric Rare Lung Disease (PRLD) is a term that refers to a heterogeneous group of Rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify ...
Bruce C. Trapnell - One of the best experts on this subject based on the ideXlab platform.
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accelerating scientific advancement for pediatric Rare Lung Disease research report from a national institutes of health nhlbi workshop september 3 and 4 2015
Annals of the American Thoracic Society, 2016Co-Authors: Lisa R. Young, Bruce C. Trapnell, Kenneth D. Mandl, Daniel T. Swarr, Jennifer A. Wambach, Carol J. BlaisdellAbstract:Pediatric Rare Lung Disease (PRLD) is a term that refers to a heterogeneous group of Rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify ...
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Accelerating Scientific Advancement for Pediatric Rare Lung Disease Research. Report from a National Institutes of Health–NHLBI Workshop, September 3 and 4, 2015
Annals of the American Thoracic Society, 2016Co-Authors: Lisa R. Young, Bruce C. Trapnell, Kenneth D. Mandl, Daniel T. Swarr, Jennifer A. Wambach, Carol J. BlaisdellAbstract:Pediatric Rare Lung Disease (PRLD) is a term that refers to a heterogeneous group of Rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify ...
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Perspectives for improving the evaluation and access of therapies for Rare Lung Diseases in Europe
Respiratory medicine, 2012Co-Authors: Maurizio Luisetti, Bruce C. Trapnell, Ian M. Balfour-lynn, Simon R. Johnson, Marc Miravitlles, Charlie Strange, Hans Van Bronswijk, Claus VogelmeierAbstract:Summary The approach to treating a Rare Disease is different to that taken for more common Diseases. Small patient cohorts alter clinical trial design and limit enrollment, and the picture for Rare Lung Diseases is further complicated by the fact that most are composed of a variety of clinical phenotypes. Since the outcome measures of Lung impairment have considerable test-to-test variability, potential new therapies face a substantial challenge. In this paper we will review the current sources of clinical data for Rare Lung Diseases and the regulatory challenges encountered by their treatment, with particular reference to alpha 1 -antitrypsin deficiency, lymphangioleiomyomatosis, cystic fibrosis, and pulmonary alveolar proteinosis. Strategies will also be identified for the better utilization of available data from patients with Rare Lung Diseases, recognizing that the development cost of new therapies and the number of patients who will ultimately use them may not be aligned. Also important is improved communication between patients and their organizations, basic researchers, clinicians and their registries, drug developers, regulators such as the European Medicines Agency, and national health services. At present, licensing and reimbursement requirements are not aligned, either nationally or internationally, and variations also exist in drug availability between countries because of different national licensing and reimbursement rules. The changes needed to optimize European Rare Lung Disease therapies include a commitment to develop empowered patient communities as advocates for therapy, the development of novel trial designs with new endpoints, and for regulatory bodies to be willing to accept nontraditional models of efficacy for orphan drugs.
Jennifer A. Wambach - One of the best experts on this subject based on the ideXlab platform.
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Childhood Rare Lung Disease in the 21st century: "-omics" technology advances accelerating discovery.
Pediatric pulmonology, 2020Co-Authors: Timothy J. Vece, Jennifer A. Wambach, James S. HagoodAbstract:Childhood Rare Lung Diseases comprise a large number of heterogeneous respiratory disorders that are individually Rare but are collectively associated with substantial morbidity, mortality, and healthcare resource utilization. Although the genetic mechanisms for several of these disorders have been elucidated, the pathogenesis mechanisms for others remain poorly understood and treatment options remain limited. Childhood Rare Lung Diseases are enriched for genetic etiologies; identification of the Disease mechanisms underlying these Rare disorders can inform the biology of normal human Lung development and has implications for the treatment of more common respiratory Diseases in children and adults. Advances in "-omics" technology, such as genomic sequencing, clinical phenotyping, biomarker discovery, genome editing, in vitro and model organism Disease modeling, single-cell analyses, cellular imaging, and high-throughput drug screening have enabled significant progress for diagnosis and treatment of Rare childhood Lung Diseases. The most striking example of this progress has been realized for patients with cystic fibrosis for whom effective, personalized therapies based on CFTR genotype are now available. In this chapter, we focus on recent technology advances in childhood Rare Lung Diseases, acknowledge persistent challenges, and identify promising new technologies that will impact not only biological discovery, but also improve diagnosis, therapies, and survival for children with these Rare disorders.
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accelerating scientific advancement for pediatric Rare Lung Disease research report from a national institutes of health nhlbi workshop september 3 and 4 2015
Annals of the American Thoracic Society, 2016Co-Authors: Lisa R. Young, Bruce C. Trapnell, Kenneth D. Mandl, Daniel T. Swarr, Jennifer A. Wambach, Carol J. BlaisdellAbstract:Pediatric Rare Lung Disease (PRLD) is a term that refers to a heterogeneous group of Rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify ...
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Accelerating Scientific Advancement for Pediatric Rare Lung Disease Research. Report from a National Institutes of Health–NHLBI Workshop, September 3 and 4, 2015
Annals of the American Thoracic Society, 2016Co-Authors: Lisa R. Young, Bruce C. Trapnell, Kenneth D. Mandl, Daniel T. Swarr, Jennifer A. Wambach, Carol J. BlaisdellAbstract:Pediatric Rare Lung Disease (PRLD) is a term that refers to a heterogeneous group of Rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify ...
Francis X. Mccormack - One of the best experts on this subject based on the ideXlab platform.
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Pulmonary alveolar microlithiasis.
European respiratory review : an official journal of the European Respiratory Society, 2020Co-Authors: Patrick Kosciuk, Cristopher A. Meyer, Kathryn A. Wikenheiser-brokamp, Francis X. MccormackAbstract:Pulmonary alveolar microlithiasis (PAM) is a fascinating Rare Lung Disease that is associated with the accumulation of hydroxyapatite microliths within the lumen of the alveolar spaces. In most patients, PAM is discovered incidentally on radiographs performed for other purposes, and the typical Disease course is characterised by slowly progressive respiratory insufficiency over decades. Recent genetic analyses that have revealed that the deficiency of the sodium-phosphate cotransporter NPT2B is the cause of PAM have enabled the development of powerful animal models that inform our approach to Disease management and treatment. Here we review the epidemiology and molecular pathophysiology of PAM, as well as the diagnostic approach, clinical manifestations, radiographic and pathologic features, and clinical management of the Disease. Although there are no proven treatments for PAM, progress in our understanding of Disease pathogenesis is providing insights that suggest strategies for trials.
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Predictors for clinical trial participation in the Rare Lung Disease lymphangioleiomyomatosis.
Respiratory medicine, 2009Co-Authors: Brent W. Kinder, Lisa R. Young, A.c. Sherman, Jared T. Hagaman, N. Oprescu, S. Byrnes, Francis X. MccormackAbstract:Summary Background Lymphangioleiomyomatosis (LAM) is a Rare, progressive and frequently lethal cystic Lung Disease that almost exclusively affects women and has no proven therapies. An improved understanding of the pathogenesis has identified promising molecular targets for clinical trials. Although barriers, modifiers, and benefits for clinical trial participation in common Diseases such as cancer have been studied, we are unaware of such evaluations concerning Rare Diseases. Methods We performed a survey of a population-based registry of 780 LAM subjects in North America to identify predictors of trial participation. Logistic regression analysis evaluated the association of demographic and clinical features with trial participation. Results 41 of 263 (16%) LAM patient respondents in North America had participated in a clinical trial. Age, Disease duration, lack of any college education, use of oxygen therapy, and presentation without chest pain were associated with trial participation in unadjusted analyses. Multivariate analyses indicate that patient age was the strongest independent predictor for trial participation (OR=2.07, p =0.004 per decade greater of patient age). Common reasons reported against trial participation included not meeting enrollment criteria (44%), drug toxicity (25%), and stable Disease (20%). The most frequent reason reported for trial participation was to help future patients (85%). Conclusions Study entry criteria, drug toxicity, and stability of Disease are barriers to trial enrollment among subjects with LAM. Older LAM patients and those with more advanced Disease are more likely to have participated in clinical trials. Altruism is commonly a motivating factor.
