Karl J Lackner

Johannes Gutenberg-Universität Mainz, Mayence, Rheinland-Pfalz, Germany

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Publications (333)1894.3 Total impact

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    ABSTRACT: There has been some dispute regarding reaction products formed at physiological peroxynitrite fluxes in the nanomolar range with phenolic molecules, when used to predict the behavior of protein-bound aromatic amino acids like tyrosine. Previous data showed that at nanomolar fluxes of peroxynitrite, nitration of these phenolic compounds was outcompeted by dimerization (e.g. biphenols or dityrosine). Using 3-morpholino sydnonimine (Sin-1), we created low fluxes of peroxynitrite in our reaction set-up to demonstrate that salicylaldehyde displays unique features in the detection of physiological fluxes of peroxynitrite, yielding detectable nitration but only minor dimerization products.
    No preview · Article · Apr 2016
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    ABSTRACT: Background: There is general consensus that the antiphospholipid syndrome (APS) is caused by antiphospholipid antibodies (aPL) with antibodies against β2-glycoprotein-I being the most relevant. aPL which bind phospholipids in the absence of protein cofactors are generally considered pathogenetically irrelevant. We showed that cofactor independent human monoclonal aPL isolated from APS patients induce proinflammatory and procoagulant cellular responses by activating endosomal NADPH-oxidase-2 (NOX2). Similar aPL were detected in all IgG-fractions from APS patients analyzed. Objectives: We aimed to clarify if cofactor independent aPL can be thrombogenic in vivo and if so, whether these effects are mediated via activation of NOX2. Methods: Two cofactor independent human monoclonal aPL, HL5B and RR7F were tested in a mouse model of venous thrombosis. Genetically modified mice and in vitro assays were used to delineate the mechanisms underlying thrombus induction. Results: HL5B and RR7F dramatically accelerate thrombus formation in this mouse model. Thrombus formation depends on tissue factor activation. It cannot be induced in NOX2-deficient mice. Bone marrow chimeras of C57BL/6J mice reconstituted with NOX2 deficient bone marrow showed that leukocyte activation plays a major role in thrombus formation. Neither TLR4 signaling nor platelet activation by our aPL are required for venous thrombus formation. Conclusions: Cofactor independent aPL can induce thrombosis in vivo. This effect is mainly mediated by leukocyte activation which depends on the previously described signal transduction via endosomal NOX2. Since most APS patients have been shown to harbor aPL with similar activity, our data are of general relevance for the APS. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jan 2016 · Journal of Thrombosis and Haemostasis
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    ABSTRACT: Background: The determination of cardiac troponin is essential for diagnosing myocardial infarction. A troponin I assay has recently been developed that provides the highest analytical sensitivity to date. Methods: The analysis included 1560 patients with chest pain, of whom 1098 were diagnosed with non-coronary chest pain, 189 with unstable angina pectoris and 273 with non-ST-segment elevation myocardial infarction. The troponin I concentration was determined on admission (0 hours) and 3 hours later. The diagnostic algorithm incorporated troponin I elevation above the gender-specific 99th percentile as well as predefined relative or absolute 3-hour changes in the troponin I concentration (delta). Results: The diagnostic criterion of troponin I above the 99th percentile resulted in a negative predictive value of 98.0% and 98.2% in men and women, respectively. For rule-in of non-ST-segment elevation myocardial infarction, the use of absolute deltas yielded higher positive predictive values and sensitivities compared to relative deltas. With detection rates of about 85% and 82% in men and women, respectively, non-ST-segment elevation myocardial infarction was diagnosed with a positive predictive value close to 84% in men and 80% in women. Conclusions: The investigational troponin I assay provides an excellent non-ST-segment elevation myocardial infarction rule out. With gender-specific differences, the application of absolute changes in troponin concentration was superior to relative changes to rule in patients with non-ST-segment elevation myocardial infarction.
    No preview · Article · Jan 2016 · European Heart Journal: Acute Cardiovascular Care
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    ABSTRACT: Context: Leptin is produced in white adipose tissue, but also in human coronary atherosclerotic lesions. Objective: The aim of this study is to assess the prognostic value of leptin in patients with proven coronary artery disease (CAD) (N = 1907). Methods: AtheroGene is a contemporary CAD cohort study (N = 3229). Median follow-up time was 3.8 (Quartile 1/3 with 2.8/4.9) years. Results: Leptin concentration was associated with a hazard ratio (HR) for the fully adjusted model of HR = 1.32 in women but was not significant in men. The endpoint cardiovascular death and non-fatal myocardial infarction was observed in 167 patients. Conclusion: In women with known CAD, increased leptin concentration is useful for predicting cardiovascular death and non-fatal myocardial infarction.
    No preview · Article · Jan 2016 · Biomarkers
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    ABSTRACT: Background: Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD. They were identified in a prospective study in relation to future myocardial infarction. Objectives: The aim of our study was to further evaluate the prognostic value of these miRNAs in a large prospective cohort of patients with documented CAD. Methods: Levels of miR-126, miR-197 and miR-223 were evaluated in serum samples of 873 CAD patients with respect to the endpoint cardiovascular death. miRNA quantification was performed using real time polymerase chain reaction (RT-qPCR). Results: The median follow-up period was 4 years (IQR 2.78-5.04). The median age of all patients was 64 years (IQR 57-69) with 80.2% males. 38.9% of the patients presented with acute coronary syndrome (ACS), 61.1% were diagnosed with stable angina pectoris (SAP). Elevated levels of miRNA-197 and miRNA-223 reliably predicted future cardiovascular death in the overall group (miRNA-197: hazard ratio (HR) 1.77 per one standard deviation (SD) increase (95% confidence interval (CI) 1.20; 2.60), p = 0.004, C-index 0.78; miRNA-223: HR 2.23 per one SD increase (1.20; 4.14), p = 0.011, C-index 0.80). In ACS patients the prognostic power of both miRNAs was even higher (miRNA-197: HR 2.24 per one SD increase (1.25; 4.01), p = 0.006, C-index 0.89); miRA-223: HR 4.94 per one SD increase (1.42; 17.20), p = 0.012, C-index 0.89). Conclusion: Serum-derived circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with CAD. These results reinforce the assumption that circulating miRNAs are promising biomarkers with prognostic value with respect to future cardiovascular events.
    No preview · Article · Dec 2015 · PLoS ONE
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    Full-text · Dataset · Dec 2015
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    ABSTRACT: Background: There are marked sex differences in cardiovascular disease (CVD) manifestation. It is largely unknown how the distribution of CVD risk factors or intermediate phenotypes explain sex-specific differences. Methods and results: In 5000 individuals of the population-based Gutenberg Health Study, mean age 55 ± 11 years, 51% males, we examined sex-specific associations of classical CVD risk factors with intima-media thickness, ankle-brachial index, flow-mediated dilation, peripheral arterial tonometry, echocardiographic, and electrocardiographic variables. Intermediate cardiovascular phenotypes were related to prevalent CVD [coronary artery disease, heart failure, stroke, myocardial infarction, lower extremity artery disease (LEAD) N = 561]. We observed differential distributions of CVD risk factors with a higher risk factor burden in men. Manifest coronary artery disease, stroke, myocardial infarction, and LEAD were more frequent in men; the proportion of heart failure was higher in women. Intermediate phenotypes showed clear sex differences with more beneficial values in women. Fairly linear changes toward less beneficial values with age were observed in both sexes. In multivariable-adjusted regression analyses, age, systolic blood pressure, and body mass index were consistently associated with intermediate phenotypes in both sexes with different ranking according to random forests, maximum model R(2) 0.43. Risk factor-adjusted associations with prevalent CVD showed some differences by sex. No interactions by menopausal status were observed. Conclusion: In a population-based cohort, we observed sex differences in risk factors and a broad range of intermediate phenotypes of non-invasive cardiovascular structure and function. Their relation to prevalent CVD differed markedly. Our results indicate the need of future investigations to understand sex differences in CVD manifestation.
    No preview · Article · Dec 2015
  • Kai Bruns · Rene Mönnikes · Karl J Lackner
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    ABSTRACT: Background: Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) utilizing triple-quadrupole instruments has been widely used for quantification of endogenous compounds, drugs or metabolites in clinical laboratories. In contrast, high-resolution mass spectrometry (HRMS) is typically used for compound identification due to its limited dynamic range. Recently HRMS instruments with enhanced linear dynamic range have become available. The aim of this study was to evaluate HRMS for fast quantitative applications in a clinical laboratory. Methods: A high throughput UPLC-TOF-MS assay for simultaneous quantification of cyclosporin A, tacrolimus, sirolimus and everolimus was developed. All immunosuppressants were analyzed as sodium adducts in TOF-only mode using an Agilent 6540 Q-TOF system. Extracted ion chromatograms of analytes and internal standards were created from full-scan data. The assay was evaluated and compared to an established LC-MS/MS assay according to CLSI recommendations. Results: The novel HRMS assay has a total run time of 3 min. The assay is linear in a clinical relevant concentration range for all four immunosupressants. Method correlations vs. established LC-MS/MS assay were between R2=0.99 and R2=0.97. Total coefficients of variation (CVT) ranges were 4.5%-6.4% (tacrolimus), 7.4%-8.0% (sirolimus), 8.0%-8.8% (everolimus) and 6.1%-7.4% (cyclosporine A) for three relevant concentration levels each. Conclusions: High resolution TOF-MS and LC-MS/MS show equivalent quantitative performance for monitoring of cyclosporin A, tacrolimus, sirolimus and everolimus. HRMS has the potential to replace conventional LC-MS/MS in clinical laboratories because it simplifies assay development (no optimization of fragmentations and product ions necessary) and its full-scan data can provide additional information.
    No preview · Article · Dec 2015 · Clinical Chemistry and Laboratory Medicine
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    ABSTRACT: Background: Intention of the study is to assess the cardiovascular mortality of patients with coronary artery disease (CAD) with the biomarkers of angiogenesis PlGF and its endogenous inhibitor sFlt-1. Methods: The cohort included n = 1848 patients with CAD and 282 subjects without CAD. In 85 patients cardiovascular mortality, as combination of fatal myocardial infarction or any cardiac death, during a median follow-up duration of 3.9 years was reported. Results: In Kaplan-Meier curve analysis PlGF in rising thirds was not predictive regarding outcome (p = 0.54), the same was shown for sFlt-1 (p = 0.44). Cox regression for the fully adjusted model provided a hazard ratio (HR) of 0.8 (p = 0.18) for PlGF and for sFlt-1 a HR = 1.0 (p = 0.8). Conclusion: Our results point out that these biomarkers reflecting angiogenesis might not be suited to establish prognosis in CAD.
    Full-text · Article · Dec 2015 · Biomarkers in Medicine
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    Full-text · Dataset · Nov 2015
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    ABSTRACT: Background: Low circulating homoarginine has been associated with adverse cardiovascular (CV) outcome and mortality in patients at risk and in the general population. The present study aimed to define plasma homoarginine reference intervals from a representative population sample to improve risk stratification between healthy individuals and individuals at risk. Methods: We determined age- and sex-specific reference intervals for circulating plasma homoarginine in a subgroup of 786 healthy participants (no CV disease or risk factors) of the Gutenberg Health Study. Homoarginine concentrations were measured using a validated liquid chromatography-tandem mass spectrometry method. Results: Median EDTA plasma homoarginine concentration was 1.88 [25th; 75th percentile, 1.47; 2.41] μmol/L, with lower concentrations in women (1.77 [1.38; 2.26] μmol/L) than in men (2.01 [1.61; 2.56] μmol/L; p<0.001). Sex-specific 2.5th and 97.5th percentiles of reference intervals were 0.84 and 3.89 μmol/L in women and 0.98 and 4.10 μmol/L in men, respectively. Homoarginine concentrations also depended on age and single nucleotide polymorphisms related to the L-arginine:glycine amidinotransferase gene. Conclusions: We provide plasma homoarginine reference intervals in men and women of the general population. The determination of homoarginine levels might be favorable for individual risk stratification.
    No preview · Article · Nov 2015 · Clinical Chemistry and Laboratory Medicine
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    ABSTRACT: Mean Platelet Volume (MPV), a measure of platelet size, is a potential biological marker of platelet function. To date, a comprehensive, combined analysis including known genetic and non-genetic factors determining MPV is still lacking. The purpose of this study is to evaluate the role of genetic and non-genetic factors for MPV variability in males and females from a large population-based cohort. MPV has been evaluated in 15,010 individuals from the population-based Gutenberg Health Study. Genetic information was available in 4,175 individuals where a full multivariable linear regression model was applied. Our results showed that age [β=0.0346, 95%CI: 0.0255;0.0436], cardiovascular risk factors (CVRFs) as smoking [β=0.178 (0.128;0.229)] and hypertension [β=0.05 (0.00289; 0.0981)] and high glucose level [β=0.00179 (0.0006;0.00299)] were linked with higher MPV in males only. Intake of oral contraceptives [β=0.150 (0.0649;0.236)] and menstruation [β=0.123 (0.0231;0.224)] were strongly associated with higher MPV in females. The linear regression analysis revealed 7 Single Nucleotide Polymorphisms (SNPs) for females and 4 SNPs for males associated with higher MPV. The full model including age, CVRFs, laboratory parameters, medications and genetic variation explained 20.4% of females and 18.6% of males MPV variance. The curves of cumulative mortality, stratified for sex, showed worse survival for males only with MPV > 9.96fL vs MPV≤ 9.96fL (p<0.0001). This study gives evidence for heterogeneity in the profile of determinants for MPV between sexes. The observed interactions between genetic variability, CVRFs and MPV and its association to the development of cardiovascular disease or thrombotic risk need to be further investigated.
    No preview · Article · Oct 2015 · Blood
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    ABSTRACT: Aims: Heme oxygenase-1 (HO-1) confers protection to the vasculature and suppresses inflammatory properties of monocytes and macrophages. It is unclear how HO-1 determines the extent of vascular dysfunction in mice and humans. Methods and results: Decreased HO-1 activity and expression was paralleled by increased aortic expression and activity of the nicotinamide dinucleotide phosphate oxidase Nox2 in HO-1 deficient Hmox1(-/-) and Hmox1(+/-) compared with Hmox1(+/+) mice. When subjected to angiotensin II-infusion, streptozotocin-induced diabetes mellitus and aging, HO-1 deficient mice showed increased vascular dysfunction inversely correlated with HO activity. In a primary prevention population-based cohort, we assessed length polymorphisms of the HMOX1 promoter region and established a bipolar frequency pattern of allele length (long vs. short repeats) in 4937 individuals. Monocytic HMOX1 mRNA expression was positively correlated with flow-mediated dilation and inversely with CD14 mRNA expression indicating pro-inflammatory monocytes in 733 hypertensive individuals of this cohort. Hmox1(-/-) mice showed drastically increased expression of the chemokine receptor CCR2 in monocytes and the aorta. Angiotensin II-infused Hmox1(-/-) mice had amplified endothelial inflammation in vivo, significantly increased aortic infiltration of pro-inflammatory CD11b(+)Ly6C(hi) monocytes and Ly6G(+) neutrophils and were marked by Ly6C(hi) monocytosis in the circulation and an increased blood pressure response. Finally, individuals with unfavourable HMOX1 gene promoter length had increased prevalence of arterial hypertension and reduced cumulative survival after a median follow-up of 7.23 years. Conclusions: Heme oxygenase-1 is a regulator of vascular function in hypertension via determining the phenotype of inflammatory circulating and infiltrating monocytes with possible implications for all-cause mortality.
    No preview · Article · Oct 2015 · European Heart Journal
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    ABSTRACT: Aims: To evaluate the diagnostic performance of high-sensitivity troponin I (hsTnI) and other novel biomarkers for diagnosing non-ST-segment elevation myocardial infarction (NSTEMI) in patients with atrial fibrillation. Methods: In an acute chest pain cohort (N=1673), mean age 61.4±13.6 (34% female), we measured hsTnI and 13 established and novel biomarkers reflecting ischaemia, necrosis, inflammation, myocardial stress, angiogenesis on admission and after three hours in order to investigate their diagnostic accuracy for NSTEMI. Results: In atrial fibrillation patients (N=299) hsTnI on admission had the best discriminatory ability for NSTEMI (area under the curve 0.97) with only two novel biomarkers, copeptin and heart-type fatty acid binding protein, having area under the curve >0.70. Measured biomarkers showed comparable discriminatory ability in atrial fibrillation and non-atrial fibrillation patients. The combination of hsTnI on admission with additional biomarkers did not clinically significantly improve diagnostic performance. In atrial fibrillation patients, hsTnI concentrations ⩽21.7 ng/L (99th percentile in a healthy German cohort) on admission gave a negative predictive value of ~100% (95% confidence interval 97-100%). The combination of hsTnI on admission and absolute change of hsTnI concentration after three hours of ⩾40 ng/L resulted in a positive predictive value of 81.2% and sensitivity of 88.6%. Diagnostic accuracy was validated in an independent cohort (N=1076). Conclusion: The diagnostic accuracy of hsTnI in patients with acute chest pain and atrial fibrillation is high and comparable to those without atrial fibrillation. Absolute change in hsTnI concentration enhanced diagnostic performance. No clinically relevant improvement was achieved by adding other biomarkers.
    Full-text · Article · Oct 2015
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    ABSTRACT: Objective: Nitric oxide produced from l-arginine is central to vascular homeostasis. Little is known about the relationship between arginine derivatives including asymmetric dimethylarginine (ADMA) and non-invasive vascular function measures in the general population. Approach and results: In 5000 individuals (median age 56; 25th/75th percentile: 46, 65; 49% women) taking part in the population-based Gutenberg Health Study (Mainz area, Germany), we measured the relationship between the arginine derivatives asymmetric dimethylarginine (ADMA), N-monomethyl l-arginine (NMMA), symmetric dimethylarginine (SDMA) and l-arginine with flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT). Weak bivariate correlations were observed between all measured arginine derivatives and vascular function measures, except of l-arginine and FMD and SDMA and PAT ratio. In multivariate adjusted linear regression analyses we could show statistically significant relationships between arginine derivatives and vascular function measures, which were influenced by age, sex and body mass index (BMI). Thus, a negative relationship between ADMA and FMD in females who were normal (beta: -0.095, P < 0.001) to overweight (beta: -0.071, P < 0.001) and a negative association of SDMA and FMD for middle-aged females was seen. The relationship between ADMA and PAT was negative for males who were normal (beta: -0.089, P < 0.001) to overweight (beta: -0.051, P = 0.007) and positive for obese females (beta: 0.073, P = 0.021). Conclusions: We showed small but significant correlations between ADMA and related arginine derivatives and non-invasive vascular function measures representative of different vascular regions. The associations were markedly influenced by age, sex and BMI. These findings support a complex interplay of arginine metabolism and vascular function.
    No preview · Article · Oct 2015 · Atherosclerosis
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    ABSTRACT: Background: -Interleukin-18 (IL-18) is a pleiotropic cytokine centrally involved in the cytokine cascade with complex immunomodulatory functions in innate and acquired immunity. Circulating IL-18 concentrations are associated with type 2 diabetes, cardiovascular events and diverse inflammatory and autoimmune disorders. Methods and results: -To identify causal variants affecting circulating IL-18 concentrations, we applied various omics and molecular biology approaches. By GWAS, we confirmed association of IL-18 levels with a SNP in the untranslated exon 2 of the inflammasome component NLRC4 (NLR family, CARD domain containing 4) gene on chromosome 2 (rs385076, P=2.4×10(-45)). Subsequent molecular analyses by gene expression analysis and reporter gene assays indicated an effect of rs385076 on NLRC4 expression and differential isoform usage by modulating binding of the transcription factor PU.1. Conclusions: -Our study provides evidence for the functional causality of SNP rs385076 within the NLRC4 gene in relation to IL-18 activation.
    No preview · Article · Sep 2015 · Circulation Cardiovascular Genetics
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    ABSTRACT: Genome-wide association studies have identified and repeatedly confirmed the association of rs3197999 in MST1 with inflammatory bowel disease (IBD). However, the underlying pathophysiology remains unclear. rs3197999 is a non-synonymous single-nucleotide polymorphism which modifies the function of macrophage stimulating protein-1 (MST1). We show by haplotyping that rs3197999 is in linkage disequilibrium with rs1050450 in GPX1, with almost complete cosegregation of the minor alleles. As shown by immunoassay, rs3197999 influences the MST-1 level in serum. But also rs1050450 causes an amino acid exchange in glutathione peroxidase 1 (GPx-1) and reduced activity of this antioxidant enzyme. The association of GPx deficiency and IBD in mice was already shown. We propose that GPx-1 is a better candidate than MST1 for the pathophysiologic link between IBD locus 12 and IBD.Genes and Immunity advance online publication, 10 September 2015; doi:10.1038/gene.2015.35.
    No preview · Article · Sep 2015 · Genes and immunity

  • No preview · Article · Sep 2015 · Pharmacopsychiatry
  • Karl J. Lackner
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    ABSTRACT: The antiphospholipid syndrome (APS) has been the subject of intensive research since its initial description as a disease entity more than 30 years ago. While significant progress in our understanding of the pathophysiology of APS has been made, many unsolved questions remain. Already in the 1990s clear evidence proved that the antiphospholipid antibodies (aPL) associated with APS cause the major clinical symptoms of the disorder, i.e. thrombotic events and abortions. This finding prompted further research into the molecular events elicited by aPL. Research focused initially on the plasmatic coagulation system. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Aug 2015 · Journal of Thrombosis and Haemostasis
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    ABSTRACT: The limit of detection (LoD) is the minimal amount of a substance that can be consistently detected. In the diagnosis of acute myocardial infarction (AMI) many patients present with troponin concentrations below the LoD of contemporary sensitive cardiac troponin I (cs-cTnI) assays. These censored values below the LoD influence the diagnostic performance of these assays compared to highly sensitive cTnI (hs-cTnI) assays. Therefore we assessed the impact of a new approach for interpolation of the left-censored data of a cs-cTnI assay in the evaluation of patients with suspected AMI. Our posthoc analysis used a real world cohort of 1818 patients with suspected MI. Data on cs-cTnI was available in 1786 patients. As a comparator the hs-cTnI version of the assay was used. To reconstruct quantities below the LoD of the cs-cTnI assay, a γ regression approach incorporating the GRACE (Global Registry of Acute Coronary Events) score variables was used. Censoring of cs-cTnI data below the LoD yielded weaker diagnostic information [area under the curve (AUC), 0.781; 95% CI, 0.731-0.831] regarding AMI compared to the hs-cTnI assay (AUC, 0.949; CI, 0.936-0.961). Use of our model to estimate cs-cTnI values below the LoD showed an AUC improvement to 0.921 (CI, 0.902-0.940). The cs-cTnI LoD concentration had a negative predictive value (NPV) of 0.950. An estimated concentration that was to be undercut by 25% of patients presenting with suspected AMI was associated with an improvement of the NPV to 0.979. Estimation of values below the LoD of a cs-cTnI assay with this new approach improves the diagnostic performance in evaluation of patients with suspected AMI. © 2015 American Association for Clinical Chemistry.
    No preview · Article · Jul 2015 · Clinical Chemistry

Publication Stats

9k Citations
1,894.30 Total Impact Points

Institutions

  • 2001-2016
    • Johannes Gutenberg-Universität Mainz
      • • Institute of Inorganic and Analytical Chemistry
      • • III. Department of Medicine
      • • Institute of Organic Chemistry
      Mayence, Rheinland-Pfalz, Germany
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 2009-2015
    • Universitätsklinikum Freiburg
      • Institute of Clinical Chemistry and Laboratory Medicine
      Freiburg an der Elbe, Lower Saxony, Germany
  • 2013
    • Queen Mary, University of London
      • Barts and The London School of Medicine and Dentistry
      Londinium, England, United Kingdom
  • 2012
    • Goethe-Universität Frankfurt am Main
      • Center for Internal Medicine
      Frankfurt, Hesse, Germany
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • University of California, San Diego
      San Diego, California, United States
  • 2005
    • Charité Universitätsmedizin Berlin
      • Institute of Clinical Physiology
      Berlin, Land Berlin, Germany
    • Case Western Reserve University
      • Department of Biochemistry
      Cleveland, Ohio, United States
  • 2004-2005
    • State University of New York Downstate Medical Center
      • Department of Cell Biology
      Brooklyn, New York, United States
  • 1994-2005
    • Universität Regensburg
      • • Department of Clinical Chemistry and Laboratory Medicine
      • • Department of Internal Medicine I
      Ratisbon, Bavaria, Germany
    • Deutsche Vereinte Gesellschaft für Klinische Chemie und Laboratoriumsmedizin e.V.
      Ratisbon, Bavaria, Germany
  • 1997-2001
    • University Hospital Regensburg
      • Klinik und Poliklinik für Innere Medizin I
      Ratisbon, Bavaria, Germany
  • 1999
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      • Department of Ophthalmology
      Erlangen, Bavaria, Germany
  • 1993
    • National Food and Nutrition Institute
      Warszawa, Masovian Voivodeship, Poland