Katharina da Silva Lopes

Faculty & Position:Public Health  instructor
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Last Updated: Aug. 28, 2020 at 05:09

Researcher Profile & Settings

Education

  • Oct. 2015Dec. 2019London School of Hygiene & Tropical Medicine/University of London/
  • Feb. 2008Oct. 2011Freie Universität Berlin/ Max-Delbrück-Center for Molecular Medicine/
  • Sep. 2001Jul. 2007University of Potsdam/ German Institute of Human Nutrition/

Academic & Professional Experience

  • Apr. 2019- TodayJunior Associate Professor, Graduate School of Public Health/, St. Luke's International University/
  • Apr. 2017Mar. 2019Assistant Professor, Global Health Nursing/, St. Luke's International University/
  • Apr. 2015Mar. 2017Research Fellow, Department of Health Policy/, National Center for Child Health and Development/
  • Jan. 2015Mar. 2015Intern, Department of Nutrition for Health and Development/, World Health Organization/
  • Jun. 2012Dec. 2014Project Researcher, Department of Cardiovascular Medicine/, University of Tokyo/

Qualification

  • PhD(Freie Universität Berlin), MSc(University of Potsdam)

Research Activities

Research Areas

  • Life sciences / Nutrition and health science

Research Interests

    Non-communicable disease prevention , Maternal and child health , Nutrition

Published Papers

  • Resolving titin's lifecycle and the spatial organization of protein turnover in mouse cardiomyocytes.
    Franziska Rudolph, Judith Hüttemeister, Katharina da Silva Lopes, René Jüttner, Lily Yu, Nora Bergmann, Dhana Friedrich, Stephan Preibisch, Eva Wagner, Stephan E Lehnart, Carol C Gregorio, Michael Gotthardt
    Proceedings of the National Academy of Sciences of the United States of America 116(50) 25126-25136 Dec. 2019 [Refereed]
    Cardiac protein homeostasis, sarcomere assembly, and integration of titin as the sarcomeric backbone are tightly regulated to facilitate adaptation and repair. Very little is known on how the >3-MDa titin protein is synthesized, moved, inserted into sarcomeres, detached, and degraded. Here, we generated a bifluorescently labeled knockin mouse to simultaneously visualize both ends of the molecule and follow titin's life cycle in vivo. We find titin mRNA, protein synthesis and degradation compartmentalized toward the Z-disk in adult, but not embryonic cardiomyocytes. Originating at the Z-disk, titin contributes to a soluble protein pool (>15% of total titin) before it is integrated into the sarcomere lattice. Titin integration, disintegration, and reintegration are stochastic and do not proceed sequentially from Z-disk to M-band, as suggested previously. Exchange between soluble and integrated titin depends on titin protein composition and differs between individual cardiomyocytes. Thus, titin dynamics facilitate embryonic vs. adult sarcomere remodeling with implications for cardiac development and disease.
  • TNF-α blockers for the treatment of Kawasaki disease in children.
    Noyuri Yamaji, Katharina da Silva Lopes, Tetsuo Shoda, Kazue Ishitsuka, Tohru Kobayashi, Erika Ota, Rintaro Mori
    The Cochrane database of systematic reviews 8 CD012448 Aug. 2019 [Refereed]
    BACKGROUND: Kawasaki disease (KD) is an acute inflammatory vasculitis (inflammation of the blood vessels) that mainly affects children between six months and five years of age. The vasculitis primarily impacts medium-sized blood vessels, especially in the coronary arteries. In most children, intravenous immunoglobulin (IVIG) and aspirin therapy rapidly reduce inflammatory markers, fever, and other clinical symptoms. However, approximately 15% to 20% of children receiving the initial IVIG infusion show persistent or recurrent fever and are classified as IVIG-resistant. Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that plays an important role in host defence against infections and in immune responses. Several studies have established that blocking TNF-α is critical for obtaining anti-inflammatory effects in children with KD, thus, there is a need to identify benefits and risks of TNF-α blockers for the treatment of KD. OBJECTIVES: To evaluate the efficacy and safety of using TNF-α blockers (i.e. infliximab and etanercept) to treat children with Kawasaki disease. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 19 September 2018. We also undertook reference checking of grey literature. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared TNF-α blockers (i.e. infliximab and etanercept) to placebo or other drugs (including retreatment with IVIG) in children with KD, reported in abstract or full-text. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the study selection criteria, assessed risk of bias and extracted data. When necessary, we contacted study authors for additional information. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included five trials from 14 reports, with a total of 494 participants. All included trials were individual RCTs that examined the effect of TNF-α blockers for KD.Five trials (with 494 participants) reported the incidence of treatment resistance. TNF-α blockers reduced the incidence of treatment resistance (TNF-α blocker intervention group 30/237, control group 58/257; risk ratio (RR) 0.57, 95% confidence interval (CI) 0.38 to 0.86; low-certainty evidence).Four trials reported the incidence of coronary artery abnormalities (CAAs). Three trials (with 270 participants) contributed data to the meta-analysis, since we could not get the data needed for the analysis from the fourth trial. There was no clear difference between groups in the incidence of CAAs (TNF-α blocker intervention group 8/125, control group 9/145; RR 1.18, 95% CI 0.45 to 3.12; low-certainty evidence).Three trials with 250 participants reported the adverse effect 'infusion reactions' after treatment initiation. The TNF-α blocker intervention decreased infusion reactions (TNF-α blocker intervention group 0/126, control group 15/124; RR 0.06, 95% CI 0.01 to 0.45; low-certainty evidence).Two trials with 227 participants reported the adverse effect 'infections' after treatment initiation. There was no clear difference between groups (TNF-α blocker intervention group 7/114, control group 10/113; RR 0.68, 95% CI 0.33 to 1.37; low-certainty evidence).One trial (with 31 participants) reported the adverse effect 'cutaneous reactions' (rash and contact dermatitis). There was no clear difference between the groups for incidence of rash (TNF-α blocker intervention group 2/16, control group 0/15; RR 4.71, 95% CI 0.24 to 90.69; very low-certainty evidence) or for incidence of contact dermatitis (TNF-α blocker intervention group 1/16, control group 3/15; RR 0.31, 95% CI 0.04 to 2.68; very low-certainty evidence).No trials reported other adverse effects such as injection site reactions, neutropenia, infections, demyelinating disease, heart failure, malignancy, and induction of autoimmunity. AUTHORS' CONCLUSIONS: We found a limited number of RCTs examining the effect of TNF-α blockers for KD. In summary, low-certainty evidence indicates that TNF-α blockers have beneficial effects on treatment resistance and the adverse effect 'infusion reaction' after treatment initiation for KD when compared with no treatment or additional treatment with IVIG. Further research will add to the evidence base. Due to the small number of underpowered trials contributing to the analyses, the results presented should be treated with caution. Further large high quality trials with timing and type of TNF-α blockers used are needed to determine the effects of TNF-α blockers for KD.
  • Nutrition-specific interventions for preventing and controlling anaemia through the life cycle: an overview of systematic reviews (Protocol)
    da Silva Lopes K, Takemoto Y, Garcia-Casal MN, Ota E
    Cochrane Database Syst Rev 8 Aug. 2018 [Refereed]
  • Altered Contractility of Skeletal Muscle in Mice Deficient in Titin's M-Band Region
    Coen A. C. Ottenheijm, Carlos Hidalgo, Katharina Rost, Michael Gotthardt, Henk Granzier
    JOURNAL OF MOLECULAR BIOLOGY 393(1) 10-26 Oct. 2009 [Refereed]
    We investigated the contractile phenotype of skeletal muscle deficient in exons MEx1 and MEx2 (KO) of the titin M-band by using the cre-lox recombination system and a multidisciplinary physiological approach to study skeletal muscle contractile performance. At a maximal tetanic stimulation frequency, intact KO extensor digitorum longus muscle was able to produce wild-type levels of force. However, at submaximal stimulation frequency, force was reduced in KO mice, giving rise to a rightward shift of the force-frequency curve. This rightward shift of the force-frequency curve could not be explained by altered sarcoplasmic reticulum Ca(2+) handling, as indicated by analysis of Ca(2+) transients in intact myofibers and expression of Ca(2+)-handling proteins, but can be explained by the reduced myofilament Ca(2+) sensitivity of force generation that we found. Western blotting experiments suggested that the excision of titin exons MEx1 and MEx2 did not result in major changes in expression of titin M-band binding proteins or phosphorylation level of the thin-filament regulatory proteins, but rather in a shift toward expression of slow isoforms; of the thick-filament-associated protein, myosin binding protein-C. Extraction of myosin binding protein-C from skinned muscle normalized myofilament Ca(2+) sensitivity of the KO extensor digitorum longus muscle. Thus, our data suggest that the M-band region of titin affects the expression of genes involved in the regulation of skeletal muscle contraction. (C) 2009 Published by Elsevier Ltd.
  • Truncation of Titin's Elastic PEVK Region Leads to Cardiomyopathy With Diastolic Dysfunction
    Henk L. Granzier, Michael H. Radke, Jun Peng, Dirk Westermann, O. Lynne Nelson, Katharina Rost, Nicholas M. P. King, Qianli Yu, Carsten Tschoepe, Mark McNabb, Douglas F. Larson, Siegfried Labeit, Michael Gotthardt
    CIRCULATION RESEARCH 105(6) 557-U126 Sep. 2009 [Refereed]
    Rationale: The giant protein titin plays key roles in myofilament assembly and determines the passive mechanical properties of the sarcomere. The cardiac titin molecule has 2 mayor elastic elements, the N2B and the PEVK region. Both have been suggested to determine the elastic properties of the heart with loss of function data only available for the N2B region. Objective: The purpose of this study was to investigate the contribution of titin's proline-glutamate-valine-lysine ( PEVK) region to biomechanics and growth of the heart. Methods and Results: We removed a portion of the PEVK segment (exons 219 to 225; 282 aa) that corresponds to the PEVK element of N2B titin, the main cardiac titin isoform. Adult homozygous PEVK knockout ( KO) mice developed diastolic dysfunction, as determined by pressure-volume loops, echocardiography, isolated heart experiments, and muscle mechanics. Immunoelectron microscopy revealed increased strain of the N2B element, a spring region retained in the PEVK-KO. Interestingly, the PEVK-KO mice had hypertrophied hearts with an induction of the hypertrophy and fetal gene response that includes upregulation of FHL proteins. This contrasts the cardiac atrophy phenotype with decreased FHL2 levels that result from the deletion of the N2B element. Conclusions: Titin's PEVK region contributes to the elastic properties of the cardiac ventricle. Our findings are consistent with a model in which strain of the N2B spring element and expression of FHL proteins trigger cardiac hypertrophy. These novel findings provide a molecular basis for the future differential therapy of isolated diastolic dysfunction versus more complex cardiomyopathies. ( Circ Res. 2009; 105: 557-564.)

Research Grants & Projects

  • Systematic review of the effectiveness of aromatherapy in labor
  • Does assistive technology improve patient’s self-medication adherence and outcome? A Systematic Review
  • Supporting the Decision-Making of Children with Cancer: A Meta-Synthesis
  • Providing linkage to breastfeeding support to mothers on discharge to improve breastfeeding outcomes: a systematic review
  • Associating gestational weight gain and infant perinatal outcomes by pre-pregnancy body mass index: a systematic review and meta-analysis
  • Antenatal interventions for preventing stillbirth: an overview of Cochrane systematic reviews
  • Nutrition-specific interventions for preventing and controlling anaemia throughout the life cycle: an overview of systematic reviews
  • Knowledge translation to reduce low birthweight infants in low BMI Japanese pregnant women using a comic book: a randomized controlled trial


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