Lynn M Schnapp

Medical University of South Carolina, Charleston, South Carolina, United States

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Publications (82)297.08 Total impact


  • No preview · Article · Mar 2015 · Annals of the American Thoracic Society
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    ABSTRACT: Introduction: Individual fellowship programs are challenged to find a format of training that not only meets the Accreditation Council for Graduate Medical Education requirements, but also grooms fellows to be trusted clinicians, and encourages them to enter academic careers. This study was undertaken as part of an internal effort to evaluate and revise the program structure of the pulmonary/critical care medicine fellowship at the Medical University of South Carolina. Our objectives were to characterize variation in the training structure and specifically research opportunities of university pulmonary/critical care medicine fellowship programs, and to identify factors associated with fellow retention in academic medicine and research. Methods: A 30-item survey was developed through rigorous internal review and was administered via email. Descriptive statistics, Cronbach's alpha, correlations, Wilcoxon sign-rank test, and ANOVA were carried out. Results: We had a response rate of 52%. Program directors reported that, within the past 5 years, 38% of their fellows remained in academic medicine and 20% remained in academics with significant research focus. We found a statistically significant association between obtaining a master's degree and remaining in academics (r = 0.559; P < 0.008). The survey also revealed statistically significant relationships between scholarly requirements (grant proposals, peer-reviewed original research projects) and the percent of fellows who graduated and remained in academics. Conclusions: This survey offers some insights that may be useful to fellowship program directors. In particular, advanced education in research and maximizing scholarly activities might be associated with increased academic retention among fellowship trainees.
    No preview · Article · Feb 2015
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    ABSTRACT: Cysteine-rich protein-61 (CYR61), also known as CCN1, is a heparin-binding protein member of the CCN family of matricellular proteins. Gene expression profiles showed that Cyr61 is upregulated in acute human lung injury (ALI), but its functional role is unclear. We hypothesized that CYR61 contributes to ALI in mice. First, we demonstrated that CYR61 expression increases after bleomycin-induced lung injury. We then used adenovirus-mediated gene transfer to determine whether CYR61 over-expression in the lungs was sufficient to cause ALI. Mice instilled with adenovirus AdCyr61 showed greater weight loss, increased bronchoalveolar lavage (BAL) total neutrophil counts, increased protein concentrations and increased mortality compared to mice instilled with empty vector adenovirus. Immunohistochemical studies in lungs from humans with idiopathic pulmonary fibrosis (IPF) revealed CYR61 expression on the luminal membrane of alveolar epithelial cells in areas of injury. We conclude that CYR61 is upregulated in ALI and that CYR61 over-expression exacerbates ALI in mice. Copyright © 2014, American Journal of Physiology - Lung Cellular and Molecular Physiology.
    Preview · Article · Feb 2015 · AJP Lung Cellular and Molecular Physiology
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    ABSTRACT: We provide a review of proteomic techniques used to characterize the bronchoalveolar lavage fluid (BALF) proteome of normal healthy subjects. Bronchoalveolar lavage (BAL) is the most common technique for sampling the components of the alveolar space. The proteomic techniques used to study normal BALF include protein separation by 2D gel electrophoresis whereby proteins were identified by comparison to a reference gel as well as high pressure liquid chromatography (HPLC)-tandem mass spectrometry technique, also known as shotgun proteomics. We summarize recent progress using shotgun MS technologies to define the normal BALF proteome. Surprisingly, we find that despite advances in shotgun proteomic technologies over the course of the last ten years, which have resulted in greater numbers of proteins being identified, the functional landscape of normal BALF proteome was similarly described by all methods examined. This article is protected by copyright. All rights reserved.
    No preview · Article · Oct 2014 · PROTEOMICS - CLINICAL APPLICATIONS
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    ABSTRACT: Background: The association between HIV and emphysema remains incompletely understood. We sought to determine whether HIV is an independent risk factor for emphysema severity and whether markers of HIV severity and systemic biomarkers of inflammation (IL-6), altered coagulation (D-dimer), and immune activation (soluble CD14) are associated with emphysema. Methods: We performed a cross-sectional analysis of 114 participants with HIV infection and 89 participants without HIV infection in the Examinations of HIV-Associated Lung Emphysema (EXHALE) study. Participants underwent chest CT imaging with blinded semiquantitative interpretation of emphysema severity, distribution, and type. We generated multivariable logistic regression models to determine the risk of HIV for radiographic emphysema, defined as > 10% lung involvement. Similar analyses examined associations of plasma biomarkers, HIV RNA, and recent and nadir CD4 cell counts with emphysema among participants with HIV infection. Results: Participants with HIV infection had greater radiographic emphysema severity with increased lower lung zone and diffuse involvement. HIV was associated with significantly increased risk for > 10% emphysema in analyses adjusted for cigarette smoking pack-years (OR, 2.24; 95% CI, 1.12-4.48). In multivariable analyses restricted to participants with HIV infection, nadir CD4 < 200 cells/μL (OR, 2.98; 95% CI, 1.14-7.81), and high soluble CD14 level (upper 25th percentile) (OR, 2.55; 95% CI, 1.04-6.22) were associated with increased risk of > 10% emphysema. IL-6 and D-dimer were not associated with emphysema in HIV. Conclusions: HIV is an independent risk factor for radiographic emphysema. Emphysema severity was significantly greater among participants with HIV infection. Among those with HIV, nadir CD4 < 200 cells/μL and elevated soluble CD14 level were associated with emphysema, highlighting potential mechanisms linking HIV with emphysema.
    No preview · Article · Jul 2014 · Chest

  • No preview · Conference Paper · May 2014
  • Chi Hung · Nicholas M Mark · Yu-Hua Chow · Lynn M. Schnapp

    No preview · Conference Paper · May 2014
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    ABSTRACT: Optimal skin wound healing relies on tight balance between collagen synthesis and degradation in new tissue formation and remodeling phases. The endocytic receptor uPARAP regulates collagen uptake and intracellular degradation. In this study we examined cutaneous wound repair response of uPARAP null (uPARAP-/-) mice. Full thickness wounds were created on dorsal surface of uPARAP-/- or their wildtype littermates. Wound healing evaluation was done by macroscopic observation, histology, gene transcription and biochemical analysis at specific intervals. We found that absence of uPARAP delayed re-epithelialization during wound closure, and altered stiffness of the scar tissue. Despite the absence of the uPARAP-mediated intracellular pathway for collagen degradation, there was no difference in total collagen content of the wounds in uPARAP-/- compared to wildtype mice. This suggests in the absence of uPARAP, a compensatory feedback mechanism functions to keep net collagen in balance.
    Full-text · Article · Mar 2014 · PLoS ONE
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    ABSTRACT: Background: The lung is an important reservoir of human immunodeficiency virus (HIV). Individuals infected with HIV are more prone to pulmonary infections and chronic lung disorders. We hypothesized that comprehensively profiling the proteomic landscape of bronchoalveolar lavage fluid (BALF) in patients with HIV would provide insights into how this virus alters the lung milieu and contributes to pathogenesis of HIV-related lung diseases. Methods: BALF was obtained from five HIV-negative (HIV(-)) and six asymptomatic HIV-positive (HIV(+)) subjects not on anti-retroviral therapy (ART). Each sample underwent shotgun proteomic analysis based on HPLC-tandem mass spectrometry. Differentially expressed proteins between the groups were identified using statistical methods based on spectral counting. Mechanisms of disease were explored using functional annotation to identify overlapping and distinct pathways enriched between the BALF proteome of HIV(+) and HIV(-) subjects. Results: We identified a total of 318 unique proteins in BALF of HIV(-) and HIV(+) subjects. Of these, 87 were differentially up or down-regulated between the two groups. Many of these differentially expressed proteins are known to interact with key HIV proteins. Functional analysis of differentially regulated proteins implicated down-regulation of immune responses in lungs of HIV(+) patients. Conclusions: Combining shotgun proteomic analysis with computational methods demonstrated that the BALF proteome is significantly altered during HIV infection. We found that immunity-related pathways are under-represented in HIV+ patients. These findings implicate mechanisms whereby HIV invokes local immunosuppression in the lung and increases the susceptibility of HIV(+) patients to develop a wide range of infectious and noninfectious pulmonary diseases.
    Preview · Article · Nov 2013 · AJP Lung Cellular and Molecular Physiology
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    Chi F Hung · Maryam G Rohani · Sung-Soon Lee · Peter Chen · Lynn M Schnapp
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    ABSTRACT: IGF-1 is elevated in pulmonary fibrosis and acute lung injury, where fibroblast activation is a prominent feature. We previously demonstrated that blockade of IGF pathway in murine model of lung fibrosis improved outcome and decreased fibrosis. We now expand that study to examine effects of IGF pathway on lung fibroblast behaviors that could contribute to fibrosis. We first examined mice that express alphaSMA promoter upstream of GFP reporter treated with A12, a blocking antibody to IGF-1 receptor, after bleomycin induced lung injury. We then examined the effect of IGF-1 alone, or in combination with the pro-fibrotic cytokine TGFbeta on expression of markers of myofibroblast activation in vitro, including alphaSMA, collagen alpha1, type 1, collagen alpha1, type III, and TGFbeta expression. After bleomycin injury, we found decreased number of alphaSMA-GFP + cells in A12 treated mice, validated by alphaSMA immunofluorescent staining. We found that IGF-1, alone or in combination with TGF-beta, did not affect alphaSMA RNA expression, promoter activity, or protein levels when fibroblasts were cultured on stiff substrate. IGF-1 stimulated Col1a1 and Col3a1 expression on stiff substrate. In contrast, IGF-1 treatment on soft substrate resulted in upregulation of alphaSMA gene and protein expression, as well as Col1a1 and Col3a1 transcripts. In conclusion, IGF-1 stimulates differentiation of fibroblasts into a myofibroblast phenotype in a soft matrix environment and has a modest effect on alphaSMA stress fiber organization in mouse lung fibroblasts.
    Preview · Article · Oct 2013 · Respiratory research
  • Beth M Hacker · Lalitha Subramanian · Lynn M Schnapp
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    ABSTRACT: Mentoring serves to guide early stage researchers toward opportunities which can further their careers. The most beneficial mentoring experience occurs when both the mentor and mentee share a common background and have appropriate expectations. Our CTSA serves individuals in a five state region with widely disparate needs and we have often struggled to provide appropriate guidance for those requesting mentoring services. Here we present an overview of our past mentor identification strategy along with a proposed new direction to increase flexibility, sustainability and better serve researchers in our region.
    No preview · Article · Oct 2013 · Clinical and Translational Science
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    ABSTRACT: Rationale: The origin of cells that make pathological fibrillar collagen matrix in lung disease has been controversial. Recent studies suggest mesenchymal cells may contribute directly to fibrosis. Objectives: 1) Characterize discrete populations of mesenchymal cells in the normal mouse lung and 2) map their fate after bleomycin-induced lung injury. Methods: We mapped the fate of Foxd1-expressing embryonic progenitors and their progeny during lung development, adult homeostasis and following fibrosing injury in Foxd1-Cre; Rs26-tdTomato-R mice. We studied Collagen-I(α)1 producing cells in normal and diseased lungs using Coll-GFPTg mice. Results: Foxd1 expressing embryonic progenitors enter lung buds before 13.5 days post conception, expand and form an extensive lineage of mesenchymal cells that have characteristics of pericytes. A Collagen-I(α)1-expressing mesenchymal population of distinct lineage is also found in adult lung, with features of a resident fibroblast. In contrast to resident fibroblasts, Foxd1 progenitor-derived pericytes are enriched in transcripts for innate immunity, vascular development, WNT signaling pathway and cell migration. Foxd1 progenitor-derived pericytes expand following bleomycin lung injury, activate expression of Collagen-I(α)1 and the myofibroblast marker αSMA in fibrotic foci. In addition, our studies suggest a distinct lineage of Collagen-I(α)1 expressing resident fibroblasts that also expands following lung injury, is a second major source of myofibroblasts. We conclude that the lung contains an extensive population of Foxd1 progenitor-derived pericytes that are an important lung myofibroblast precursor population.
    Preview · Article · Aug 2013 · American Journal of Respiratory and Critical Care Medicine

  • No preview · Conference Paper · May 2013
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    Dataset: Table S1
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    ABSTRACT: Detailed characteristics of ALI patients. (PDF)
    Preview · Dataset · Mar 2013
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    Dataset: Table S4
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    ABSTRACT: Differential BALF protein expression between Controls and ALI patients. (PDF)
    Preview · Dataset · Mar 2013
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    Dataset: Figure S1
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    ABSTRACT: Representative BALF Western blots for S100A8 showing increased expression in VAP+ patients. (PDF)
    Preview · Dataset · Mar 2013
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    ABSTRACT: Ventilator-associated pneumonia (VAP) is a common complication in patients with acute lung injury (ALI) and can lead to increased morbidity and mortality. Identifying protein profiles specific to VAP in bronchoalveolar lavage fluid (BALF) may aid in earlier diagnosis, elucidate mechanisms of disease, and identify putative targets for therapeutic intervention. BALF was obtained from 5 normal subjects and 30 ALI patients: 14 with VAP (VAP(+)) and 16 without VAP (VAP(-)). Each sample underwent shotgun proteomic analysis based on tandem mass spectrometry. Differentially expressed proteins between the groups were identified using statistical methods based on spectral counting. Mechanisms of disease were explored using functional annotation and protein interaction network analysis. Supervised classification algorithms were implemented to discover a proteomic classifier for identifying critically ill patients with VAP. ALI patients had distinct BALF proteomic profiles compared to normal controls. Within the ALI group, we identified 76 differentially expressed proteins between VAP(+) and VAP(-). Functional analysis of these proteins suggested activation of pro-inflammatory pathways during VAP. We identified and validated a limited proteomic signature that discriminated VAP(+) from VAP(-) patients comprised of three proteins: S100A8, lactotransferrin (LTF), and actinin 1 (ACTN1). Combining proteomic with computational analyses is a powerful approach to study the BALF proteome during lung injury and development of VAP. This integrative methodology is a promising strategy to differentiate clinically relevant subsets of ALI patients, including those suffering from VAP.
    Full-text · Article · Mar 2013 · PLoS ONE
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    Dataset: Table S2
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    ABSTRACT: Characteristics of patients suspected of having VAP in the validation cohort. (PDF)
    Preview · Dataset · Mar 2013
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    Dataset: Table S3
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    ABSTRACT: BALF proteome of Control subjects with spectral counts. (PDF)
    Preview · Dataset · Mar 2013
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    Dataset: Table S5
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    ABSTRACT: BALF proteome of ALI patients with and without VAP. (PDF)
    Preview · Dataset · Mar 2013

Publication Stats

2k Citations
297.08 Total Impact Points

Institutions

  • 2015
    • Medical University of South Carolina
      • Division of Pulmonary, Critical Care, Allergy & Sleep Medicine
      Charleston, South Carolina, United States
  • 2001-2015
    • University of Washington Seattle
      • • Division of Pulmonary and Critical Care Medicine
      • • Department of Medicine
      Seattle, Washington, United States
  • 1998-2005
    • Mount Sinai School of Medicine
      • • Department of Medicine
      • • Department of Pediatrics
      Manhattan, New York, United States
  • 2003
    • Yale University
      • Section of Pulmonary and Critical Care Medicine
      New Haven, Connecticut, United States
  • 1996
    • University of California, San Francisco
      • Cardiovascular Research Institute
      San Francisco, California, United States