Lars Kaderali

Lars Kaderali
University of Greifswald · Institute for Bioinformatics

Prof. Dr. rer. nat.

About

262
Publications
24,668
Reads
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4,611
Citations
Additional affiliations
September 2015 - present
University of Greifswald
Position
  • Managing Director
October 2011 - August 2015
Technische Universität Dresden
Position
  • Professor
July 2007 - October 2011
Universität Heidelberg
Position
  • Group Leader
Education
April 2001 - April 2006
University of Cologne
Field of study
  • Computer Science

Publications

Publications (262)
Preprint
The pattern recognition receptor RIG I is essential for the recognition of viral dsRNA and the activation of a cell autonomous antiviral response. Upon stimulation, RIG I triggers a signaling cascade leading to the expression of cytokines, most prominently type I and III interferons (IFNs). IFNs are secreted and signal in an auto and paracrine mann...
Preprint
Full-text available
Plus-strand RNA viruses are the largest group of viruses. Many are human pathogens that inflict a socio-economic burden. Interestingly, plus-strand RNA viruses share remarkable similarities in their replication. A hallmark of plus-strand RNA viruses is the remodeling of intracellular membranes to establish replication organelles (so-called “replica...
Article
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Background Approaching epidemiological data with flexible machine learning algorithms is of great value for understanding disease-specific association patterns. However, it can be difficult to correctly extract and understand those patterns due to the lack of model interpretability. Method We here propose a machine learning workflow that combines...
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Since autumn 2020, rapid antigen tests (RATs) have been implemented in several countries as an important pillar of the national testing strategy to rapidly screen for infections on site during the SARS-CoV-2 pandemic. The current surge in infection rates around the globe is driven by the variant of concern (VoC) omicron (B.1.1.529). Here, we evalua...
Article
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Background and purpose: Development and progression of heart failure (HF) involve endothelial and myocardial dysfunction as well as a dysregulation of the nitric oxide - soluble guanylyl cyclase - cyclic guanosine monophosphate (NO-sGC-cGMP) signalling pathway. Recently, we reported that the sGC stimulator riociguat (RIO) has beneficial effects on...
Article
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Purpose To determine risk factors for coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs), characterize symptoms, and evaluate preventive measures against SARS-CoV-2 spread in hospitals. Methods In a cross-sectional study conducted between May 27 and August 12, 2020, after the first wave of the COVID-19 pandemic, we obtained serologic...
Article
Acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis. We report a comprehensive proteogenomic analysis of bone marrow biopsies from 252 uniformly treated AML patients to elucidate the molecular pathophysiology of AML in order to inform future diagnostic and therapeutic approaches. In addition to in-depth quantitative pro...
Article
Standard cancer therapy targets tumor cells without considering possible damage on the tumor microenvironment that could impair therapy response. In rectal cancer patients we find that inflammatory cancer-associated fibroblasts (iCAFs) are associated with poor chemoradiotherapy response. Employing a murine rectal cancer model or patient-derived tum...
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Aortic valve stenosis (AVS) is one of the most common valve diseases in the world. However, detailed biological understanding of the myocardial changes in AVS hearts on the proteome level is still lacking. Proteomic studies using high-resolution mass spectrometry of formalin-fixed and paraffin-embedded (FFPE) human myocardial tissue of AVS-patients...
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Double membrane vesicles (DMVs) serve as replication organelles of plus-strand RNA viruses such as hepatitis C virus (HCV) and SARS-CoV-2. Viral DMVs are morphologically analogous to DMVs formed during autophagy, but lipids driving their biogenesis are largely unknown. Here we show that production of the lipid phosphatidic acid (PA) by acylglycerol...
Article
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The development of ‘age clocks’, machine learning models predicting age from biological data, has been a major milestone in the search for reliable markers of biological age and has since become an invaluable tool in aging research. However, beyond their unquestionable utility, current clocks offer little insight into the molecular biological proce...
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A versatile portfolio of diagnostic tests is essential for the containment of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Besides nucleic acid-based test systems and point-of-care (POCT) antigen (Ag) tests, quantitative, laboratory-based nucleocapsid Ag tests for SARS-CoV-2 have recently been launched. Here, we e...
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The importance of pre-existing immune responses to seasonal endemic coronaviruses (HCoVs) for the susceptibility to SARS-CoV-2 infection and the course of COVID-19 is subject of an ongoing scientific debate. Recent studies postulate that immune responses to previous HCoV infections can either have a slightly protective or no effect on SARS-CoV-2 pa...
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Background: Sepsis and inflammation can cause intensive care unit-acquired weakness (ICUAW). Increased interleukin-6 (IL-6) plasma levels are a risk factor for ICUAW. IL-6 signalling involves the glycoprotein 130 (gp130) receptor and the JAK/STAT-pathway, but its role in sepsis-induced muscle wasting is uncertain. In a clinical observational study...
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Background Artificial intelligence (AI) and machine learning (ML) promise vast advances in medicine. The current state of AI/ML applications in cardiovascular medicine is largely unknown. This systematic review aims to close this gap and provides recommendations for future applications. Methods Pubmed and EMBASE were searched for applied publicati...
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In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main anti-hypertensive therapies—angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)—remain unclear. Combining clinical...
Preprint
Full-text available
Double membrane vesicles (DMVs) are used as replication organelles by phylogenetically and biologically distant pathogenic RNA viruses such as hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Viral DMVs are morphologically analogous to DMVs formed during autophagy, and although the proteins required for DMV...
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In this work, we introduce an entirely data-driven and automated approach to reveal disease-associated biomarker and risk factor networks from heterogeneous and high-dimensional healthcare data. Our workflow is based on Bayesian networks, which are a popular tool for analyzing the interplay of biomarkers. Usually, data require extensive manual prep...
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Successful containment strategies for the SARS-CoV-2 pandemic will depend on reliable diagnostic assays. Point-of-care antigen tests (POCT) may provide an alternative to time-consuming PCR tests to rapidly screen for acute infections on site. Here, we evaluated two SARS-CoV-2 antigen tests: the STANDARD™ F COVID-19 Ag FIA (FIA) and the SARS-CoV-2 R...
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Background and purpose: Heart failure (HF) is associated with an impaired NO-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway, and its augmentation is thought to be beneficial in HF therapy. We hypothesized that stimulation of sGC by the sGC stimulator riociguat (Rio) prevents pathological cardiac remodelling and HF in...
Article
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Hepatitis C virus (HCV) causes acute hepatitis C and can lead to life-threatening complications if it becomes chronic. The HCV genome is a single plus strand of RNA. Its intracellular replication is a spatiotemporally coordinated process of RNA translation upon cell infection, RNA synthesis within a replication compartment, and virus particle produ...
Preprint
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In COVID-19, hypertension and cardiovascular diseases have emerged as major risk factors for critical disease progression. Concurrently, the impact of the main anti-hypertensive therapies, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), on COVID-19 severity is controversially discussed. By combining clinical...
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While ionizing radiation (IR) is a powerful tool in medical diagnostics, nuclear medicine, and radiology, it also is a serious threat to the integrity of genetic material. Mutagenic effects of IR to the human genome have long been the subject of research, yet still comparatively little is known about the genome-wide effects of IR exposure on the DN...
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The simultaneous analysis of different regulatory levels of biological phenomena by means of multi-omics data integration has proven an invaluable tool in modern precision medicine, yet many processes ultimately paving the way towards disease manifestation remain elusive and have not been studied in this regard. Here we investigated the early molec...
Article
Little is known about the mutational impact of ionizing radiation (IR) exposure on a genome-wide level in mammalian tissues. Recent advancements in sequencing technology have provided powerful tools to perform exome-wide analyses of genetic variation. This also opened up new avenues for studying and characterizing global genomic IR-induced effects....
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The primary barrier that protects our lungs against infection by pathogens is a tightly sealed layer of epithelial cells. When the integrity of this barrier is disrupted as a consequence of chronic pulmonary diseases or viral insults, bacterial pathogens will gain access to underlying tissues. A major pathogen that can take advantage of such condit...
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In recent years, reports of non-linear regulations in age- and longevity-associated biological processes have been accumulating. Inspired by methodological advances in precision medicine involving the integrative analysis of multi-omics data, we sought to investigate the potential of multi-omics integration to identify distinct stages in the aging...
Article
In cell-intrinsic antiviral immunity, cytoplasmic receptors such as retinoic acid-inducible gene I (RIG-I) detect viral double-stranded RNA (dsRNA) and trigger a signaling cascade activating the interferon (IFN) system. This leads to the transcription of hundreds of interferon-stimulated genes (ISGs) with a wide range of antiviral effects. This rec...
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Dengue virus (DV) is a positive-strand RNA virus of the Flavivirus genus. It is one of the most prevalent mosquito-borne viruses, infecting globally 390 million individuals per year. The clinical spectrum of DV infection ranges from an asymptomatic course to severe complications such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS)...
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Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have...
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Full-text available
Purpose Discrimination of uterine leiomyosarcoma (LMS) and leiomyoma (LM) prior to surgery by basic preoperative characteristics and development of a preoperative leiomyosarcoma score. Methods A predominantly prospective cohort of 826 patients with LM from a clinical institution and an outpatient center was included in the study. Further a predomi...
Article
Lentiviral vectors and lentiviruses are important tools for basic and applied biomedical research. Yet, biosafety regulations from legal authorities have to be fulfilled when transferring BSL-2 to -3 vectors/viruses to facilities with lower biosafety level. Here, we (re-)evaluated different chemical and thermal approaches to inactivate vesicular st...
Poster
Background Heart Failure (HF) is associated with endothelial dysfunction and reduced bioavailability of NO with insufficient stimulation of sGC and reduced production of cGMP. Therefore, the impairment of the NO-sGC-cGMP pathway results in vasoconstriction, platelet aggregation, inflammation, fibrosis and most importantly maladaptive cardiac hypert...
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Hypomethylating agents decitabine and azacytidine are regarded as interchangeable in the treatment of acute myeloid leukemia (AML). However, their mechanisms of action remain incompletely understood, and predictive biomarkers for HMA efficacy are lacking. Here, we show that the bioactive metabolite decitabine triphosphate, but not azacytidine triph...
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We previously reported the establishment of a rare xenograft derived from a recurrent oligodendroglioma with 1p/19q codeletion. Here, we analyzed in detail the exome sequencing datasets from the recurrent oligodendroglioma (WHO grade III, recurrent O2010) and the first-generation xenograft (xenograft1). Somatic SNVs and small InDels (n = 80) with p...
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Dengue virus (DENV) is a human arboviral pathogen accounting for 390 million infections every year. The available vaccine has limited efficacy, and DENV-specific drugs have not been generated. To better understand DENV-host cell interaction, we employed RNA interference-based screening of the human kinome and identified fibroblast growth factor rec...
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Staphylococcus aureus is infamous for causing recurrent infections of the human respiratory tract. This is a consequence of its ability to adapt to different niches, including the intracellular milieu of lung epithelial cells. To understand the dynamic interplay between epithelial cells and the intracellular pathogen, we dissected their interaction...
Article
Background and objectives Previous studies observed a transient increase in well‐being in about one‐third of regular donors after blood donation. In addition, personal contact with donors after donation seems to increase return rates. We were interested whether changes in well‐being and/or personal contact after the first donation impact return rat...
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SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase (dNTPase) that depletes cellular dNTPs in noncycling cells to promote genome stability and to inhibit retroviral and herpes viral replication. In addition to being substrates, cellular nucleotides also allosterically regulate SAMHD1 activity. Recently, it was shown that high expression le...
Article
Objective: Electrocardiography is the most common tool to diagnose cardiovascular diseases. Annotation, segmentation and rhythm classification of ECGs are challenging tasks, especially in the presence of atrial fibrillation and other arrhythmias. Our aim is to increase the accuracy of heart rhythm estimation by the use of extreme gradient boosting...
Article
Full-text available
Patients with head-and-neck cancer can develop both lung meta-stasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head-and-neck (HNSCC) carcinomas by quantitative...
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Hepatitis C virus (HCV) and the malaria parasite Plasmodium use the membrane protein CD81 to invade human liver cells. Here we mapped 33 host protein interactions of CD81 in primary human liver and hepatoma cells using high-resolution quantitative proteomics. In the CD81 protein network, we identified five proteins which are HCV entry factors or fa...
Data
Characterization of Lunet N cell lines expressing different CD81-variants. (A) Schematic representation of CD81-variants used in this study to analyze the CD81-interactome in human hepatoma cells. (B) Immunoblot analysis of CD81-expression in Lunet N derived cell lines used in this study. Protein expression was analyzed with an anti-CD81 antibody....
Data
Protein enrichment in CD81-IPs from different hepatoma cell lines. (A) Dot plot showing LFQ intensities of proteins in CD81- and HA-IPs from the indicated cell line lysed with NP-40 containing buffer. CD81 (green) and SCARB1 (black) served as positive and APOL2 (white) as negative control. Median of 4 biological replicates. (B) Pretest for choice o...
Data
Expression and KO of CAPN5 and CBLB in hepatoma cell lines. (A, B) Whole cell proteome quantification for (A) Lunet N and (B) Lunet N hCD81-HA cells. Expression level as iBAQ intensity highlighted for the CD81 interactor CAPN5 and the HCV entry factors CD81, SCARB1, CLDN1 and OCLN. (C, D) Immunofluorescence staining of (C) CAPN5 and (D) CBLB in Lun...
Data
CAPN5 and CBLB are dispensable for Plasmodium entry into hepatoma cells. Lunet N hCD81 human hepatoma cells carrying the indicated sgRNA were infected with sporozoites of P. berghei or P.yoelii GFP reporter strains for 180 min, then washed and further cultured until fixation at 36 hpi. Exoerythrocytic forms were quantified by fluorescence microscop...
Data
CD81 Organizes tyrosine kinase and small G protein signaling networks in the membrane of human liver cells. (A) Centered network depicting the 42 CD81 associated proteins identified in this study. Each node represents one protein and the length of the edges reflects the median enrichment score for each protein in CD81 co-IPs from hepatoma cells and...
Data
Graphical summary. A combined label free quantification (LFQ)–RNA interference (RNAi)–CRISPR/Cas9 workflow identifies calpain-5 (CAPN5) and Casitas B-lineage lymphoma proto-oncogene B (CBLB) as hepatitis C virus (HCV) entry factors. CAPN5 and CBLB are critical host factors for all HCV genotypes and guide virus endocytosis and endosomal trafficking....
Data
LFQ dataset for CD81 co-IPs from Lunet N cells. Protein abundances in human hepatoma cell CD81 co-IPs. Listed are all detected proteins and the intensity differences of CD81-specific and control co-IPs for the experimental condition. Please refer to Excel file. (XLSX)