About
80
Publications
11,761
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
2,932
Citations
Publications
Publications (80)
Fibroblast growth factor receptor 2b (Fgfr2b) signaling is essential throughout lung development to form the alveolar epithelial lineage. However, its role in alveolar epithelial type 2 cells (AT2s) homeostasis was recently considered dispensable. S ftpc CreERT2 ; Fgfr2b flox/flox ; tdTomato flox/flox mice were used to delete Fgfr2b expression in c...
Environmental factors, including pollutants and lifestyle, constitute a significant role in severe, chronic pathologies with an essential societal, economic burden. The measurement of all environmental exposures and assessing their correlation with effects on individual health is defined as the exposome, which interacts with our unique characterist...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is worldwide the main cause of the COVID-19 pandemic. After infection of human pulmonary cells, intracellular viral replication take place in different cellular compartments resulting in the destruction of the host cells and causing severe respiratory diseases. Although cellular traff...
Fibroblast growth factor receptor 2b (Fgfr2b) signaling is essential throughout lung development to form the alveolar epithelial lineage. However, its role in alveolar epithelial type 2 cells (AT2s) homeostasis was recently considered dispensable. SftpcCreERT2; tdTomatoflox/flox mice were used to delete Fgfr2b expression in cells belonging to the A...
The high incidence of thrombotic events suggests a possible role of the contact system pathway in COVID-19 pathology. Here, we demonstrate altered levels of factor XII (FXII) and its activation products in critically ill COVID-19 patients in comparison to patients with severe acute respiratory distress syndrome due to influenza virus (ARDS-influenz...
The high incidence of thrombotic events suggests a possible role of the contact system pathway in COVID-19 pathology. Here, we demonstrate altered levels of factor XII (FXII) and its activation products in two independent cohorts of critically ill COVID-19 patients in comparison to patients suffering from severe acute respiratory distress syndrome...
Lymphoid-specific helicase (LSH) is a member of the SNF2 helicase family of chromatin-remodelling proteins. Dysfunctions or mutations in LSH causes an autosomal recessive disease known as immunodeficiency-centromeric instability-facial anomaly (ICF) syndrome. Interestingly, LSH participates in various aspects of epigenetic regulation, including nuc...
Sex-dependent differences in immunity and coagulation play an active role in the outcome of community-acquired pneumonia (CAP). Contact phase proteins act at the crossroads between inflammation and coagulation thus representing a point of convergence in host defense against infection. Here, we measured the levels of factor XII (FXII), FXIIa-C1 este...
In addition to nucleosomes, chromatin contains non-histone chromatin-associated proteins, of which the high-mobility group proteins are the most abundant. Chromatin-mediated regulation of transcription involves DNA methylation and histone modifications. However, the order of events and the precise function of high-mobility group proteins during tra...
Background: Sex-dependent differences in immunity and coagulation play an active role in 28 the outcome of community-acquired pneumonia (CAP). Factor XII acts at the crossroads 29 between inflammation and coagulation thus representing a point of convergence in host 30 defense against infection. Here, we evaluated FXII/FXIIa levels in plasma of CAP...
Although NF-ƙB is known to play a pivotal role in lung cancer, contributing to tumor growth, microenvironmental changes, and metastasis, the epigenetic regulation of NF-ƙB in tumor context is largely unknown. Here we report that the IKK2/NF-ƙB signaling pathway modulates metastasis-associated protein 2 (MTA2), a component of the nucleosome remodeli...
Objectives:
There is a high unmet need in a non-invasive screening of lung cancer (LC). We conducted this single-center trial to evaluate the effectiveness of the electronic nose Aeonose®. The Aeonose collects breath samples for analysis of volatile organic compound (VOC) signatures, determined by a pattern of resistance changes caused by differen...
Background:
Bronchopulmonary dysplasia (BPD) is a lung disease of preterm born infants, characterized by alveolar simplification. MicroRNA (miR) are known to be involved in many biological and pathological processes in the lung. Although a changed expression has been described for several miR in BPD, a causal role remains to be established.
Resul...
In addition to nucleosomes, chromatin also contains non-histone chromatin-associated proteins, of which the high-mobility group (HMG) proteins are the most abundant. Chromatin-mediated regulation of transcription involves DNA methylation and histone modifications. However, the order of events and the precise function of HMG proteins during transcri...
In healing tissue, fibroblasts differentiate to α-smooth muscle actin (SMA)-expressing contractile-myofibroblasts, which pull the wound edges together ensuring proper tissue repair. Uncontrolled expansion of the myofibroblast population may, however, lead to excessive tissue scarring and finally to organ dysfunction. Here, we demonstrate that the l...
Background:
There is an increasing interest in employing electronic nose technology in the diagnosis and monitoring of lung diseases. Interstitial lung diseases (ILD) are challenging in regard to setting an accurate diagnosis in a timely manner. Thus, there is a high unmet need in non-invasive diagnostic tests. This single-center explorative study...
The respiratory epithelium arises from alveolar epithelial progenitors which differentiate into alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. AT2 cells are stem cells in the lung critical for the repair process after injury. Mechanisms regulating AT1 and AT2 cell maturation are poorly defined. We report that the activation of the glucoco...
Although abnormal nuclear structure is an important criterion for cancer diagnostics, remarkably little is known about its relationship to tumor development. Here we report that loss of lamin B1, a determinant of nuclear architecture, plays a key role in lung cancer. We found that lamin B1 levels were reduced in lung cancer patients. Lamin B1 silen...
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and highly lethal lung disease with unknown etiology and poor prognosis. IPF patients die within 2 years after diagnosis mostly due to respiratory failure. Current treatments against IPF aim to ameliorate patient symptoms and to delay disease progression. Unfortunately, therapies target...
Generation of widely differing and specialized cell types from a single totipotent zygote involves large-scale transcriptional changes and chromatin reorganization. Pioneer transcription factors play key roles in programming the epigenome and facilitating recruitment of additional regulatory factors during successive cell lineage specification and...
The eukaryotic cell nucleus consists of functionally specialized subcompartments. These nuclear subcompartments are biomolecular aggregates built of proteins, transcripts, and specific genome loci. The structure and function of each nuclear subcompartment are defined by the composition and dynamic interaction between these 3 components. The spatio-...
Accumulation of mutations causing aberrant changes in the genome promotes cancer. However, mutations do not occur in every cancer subtype, suggesting additional events that trigger cancer. Chromatin rearrangements initiated by pioneer factors and architectural proteins are key events occurring before cancer-related genes are expressed. Both protein...
The majority of the eukaryotic genome is transcribed into noncoding RNAs (ncRNAs), which are important regulators of different nuclear processes by controlling chromatin structure. However, the full extent of ncRNA function has remained elusive. Here we deciphered the function of the microRNA Mirlet7d as a key regulator of bidirectionally transcrib...
The development of a functional lung, capable of gas exchange, requires proper alveologenesis. Mechanisms regulating AT1 and AT2 cell maturation are poorly defined. We report the activation of the glucocorticoid pathway in an in vitro alveolar epithelial lineage differentiation assay led to increased AT2 marker Sftpc and decreased miR-142 expressio...
Lung cancer is the leading cause of cancer-related deaths worldwide. The case-fatality rate of lung cancer remains exceptionally high at 95% despite numerous medical advancements in therapeutic strategies in the last decades. However, patients diagnosed at Stage I are commonly curable and have a 5-year survival rate of 50–80%. Unfortunately, delaye...
Expanded View Figures PDF
Tables EV1–EV4
Review Process File
Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Early LC diagnosis is crucial to reduce the high case fatality rate of this disease. In this case-control study, we developed an accurate LC diagnosis test using retrospectively collected formalin-fixed paraffin-embedded (FFPE) human lung tissues and prospectively collected e...
Inflammation-induced FGF10 protein deficiency is associated with bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurely born infants characterized by arrested alveolar development. So far, experimental evidence for a direct role of FGF10 in lung disease is lacking. Using the hyperoxia-induced neonatal lung injury as a mouse model o...
RAS proteins function as molecular switches that transmit signals from cell surface receptors into specific cellular responses via activation of defined signaling pathways (Fang, 2015). Aberrant constitutive RAS activation occurs with high incidence in different types of cancer (Bos, 1989). Thus, inhibition of RAS-mediated signaling is extremely im...
microRNA-142 (miR-142) is an important regulator of many biological processes and associated signaling pathways during embryonic development, homeostasis and disease. The miR-142 hairpin gives rise to the "guide strand" miR-142-3p and the sister "passenger" strand miR-142-5p. miR-142-3p has been shown to play critical, non-redundant functions in th...
The eukaryotic genome is organized into chromatins, the physiological template for DNA-dependent processes including replication, recombination, repair, and transcription. Chromatin-mediated transcription regulation involves DNA methylation, chromatin remodeling, and histone modifications. However, chromatin also contains non-histone chromatin-asso...
Lung cancer is the leading cause of cancer-related deaths worldwide. The initiation and progression of lung cancer is the result of the interaction between permanent genetic and dynamic epigenetic alterations. DNA methylation is the best studied epigenetic mark in human cancers. Altered DNA methylation in cancer was identified in 1983. Within 30 ye...
The expression ratio between the analysed gene and an internal control gene is the most widely used normalization method for quantitative RT-PCR (qRT-PCR) expression analysis. The ideal reference gene for a specific experiment is the one whose expression is not affected by the different experimental conditions tested. In this study, we validate the...
Today, the targeted drug delivery to tumors is one of the leading researches in anticancer therapy. Using gene engineering techniques the new expression system based on pCS2+ vector was created. Gene of Bacillus pumilis ribonuclease - binase, and gene of intracellular inhibitor of Bacillus amyloliquefaciens - barstar were cloned under promotor of c...
Despite optimal therapy, the morbidity and mortality of patients presenting with an acute myocardial infarction (MI) remain significant, and the initial mechanistic trigger of myocardial "ischaemia/reperfusion (I/R) injury" remains greatly unexplained. Here we show that factors released from the damaged cardiac tissue itself, in particular extracel...
The high-mobility-group (HMG) proteins are the most abundant non-histone chromatin-associated proteins. HMG proteins are present at high levels in various undifferentiated tissues during embryonic development and their levels are strongly reduced in the corresponding adult tissues, where they have been implicated in maintaining and activating stem/...
High mobility group (HMG) proteins are the most abundant non-histone chromatin associated proteins. HMG proteins bind to DNA and nucleosome and alter the structure of chromatin locally and globally. Accessibility to DNA within chromatin is a central factor that affects DNA-dependent nuclear processes, such as transcription, replication, recombinati...
The regulation of the balance between proliferation and differentiation in the mesenchymal compartment of the lung is largely uncharacterized, unlike its epithelial counterpart. In this study, we determined that miR-142-3p contributes to the proper proliferation of mesenchymal progenitors by controlling the level of WNT signaling. miR-142-3p can ph...
A Mexican airline pilot had clinical manifestations of illness after a five-day stay in Lima, Peru. Six months later in Mexico, he was given a diagnosis of infection with Cyclospora cayetanensis by using coproparasitoscopic serial tests. He was treated twice with nitazoxadine successfully.
Alveolar type II cells (ATII cells) are lung progenitor cells responsible for regeneration of alveolar epithelium during homeostatic turnover and in response to injury. Characterization of ATII cells will have a profound impact on our understanding and treatment of lung disease. The identification of novel ATII cell surface proteins can be used for...
The vertebrate limbs develop through coordinated series of inductive, growth and patterning events. Fibroblast Growth Factor receptor 2b (FGFR2b) signaling controls the induction of the Apical Ectodermal Ridge (AER) but its putative roles in limb outgrowth and patterning, as well as in AER morphology and cell behavior have remained unclear. We have...
Microbial ribonucleases possess a broad spectrum of biological activities, which demonstrate stimulating properties at low concentrations and cytotoxicity and genotoxicity at high concentrations. Mechanisms of their penetration into the cells still remain unclear. In this study penetration of Bacillus intermedius RNase (binase) in alveolar lung epi...
Neutrophils play an important role in innate immunity by defending the host organism against invading microorganisms. Antimicrobial activity of neutrophils is mediated by release of antimicrobial peptides, phagocytosis as well as formation of neutrophil extracellular traps (NET). These structures are composed of DNA, histones and granular proteins...
Identified up-regulated proteins in A549 cells after incubation with NET. A549 cells were treated with NET, and the up-regulated proteins were identified by MALDI-TOF-MS. A wide range of proteins with different functions and cellular localizations were up-regulated. Roles in cell death for several proteins (indicated by a) have been reported based...
APC degrades isolated histones but not NET-associated proteins. (A) SDS-gel electrophoresis (15%) of histones and (B) NET proteins before or after incubation with 100 nM APC were carried out, and several bands were identified with MALDI-TOF-MS. In (A) 10 times higher amount of APC was loaded as a control. (C) 2-D gel electrophoresis (pH 7–11) of NE...
Identified NET proteins by 2-D gel electrophoresis and MALDI-TOF-MS. 2-D gel electrophoresis was performed for NET-proteins with isoelectric focusing at different pH ranges (3–10 and 7–11). From 32 randomly chosen spots in NET, we identified 13 different proteins from which 9 proteins have been already described by Urban and co-workers [7]. Four di...