Nikolaus Fortelny

Nikolaus Fortelny
University of Salzburg · Biosciences

Ph.D.

About

66
Publications
11,818
Reads
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1,215
Citations
Additional affiliations
September 2020 - September 2020
University of Salzburg
Position
  • Professor (Assistant)
Description
  • Group Leader - Computational Systems Biology
August 2016 - August 2020
CeMM Research Center for Molecular Medicine
Position
  • PostDoc Position
January 2012 - July 2016
University of British Columbia - Vancouver
Position
  • PhD Student
Description
  • Global (network-like) interactions between proteases and their inhibitors via cleavage and inhibition interactions in the “Protease Web”, (co-)expression of protease and inhibitors, and other protein-protein interactions
Education
January 2012 - August 2015
University of British Columbia - Vancouver
Field of study
  • Computational Biology, Biochemistry, Protease Biology
September 2008 - July 2010
University of Geneva
Field of study
  • Bioinformatics and Proteomics
September 2005 - July 2009
University of Vienna
Field of study
  • Molecular Biology

Publications

Publications (66)
Preprint
Interactions between transcription factors (TF) and chromatin factors (CF) regulate gene expression programmes to determine cellular fate. However, unlike for TF, the exact role of CF in this process is poorly understood. Using haematopoiesis as a model system and utilising novel functional CRISPR screens ex vivo and in vivo, coupled with Perturb-S...
Preprint
Methylation of cytosines is the prototypic epigenetic modification of the DNA. It has been implicated in various regulatory mechanisms throughout the animal kingdom and particularly in vertebrates. We mapped DNA methylation in 580 animal species (535 vertebrates, 45 invertebrates), resulting in 2443 genome-scale, base-resolution DNA methylation pro...
Chapter
Proteases regulate other proteases directly via cleavage or indirectly via cleavage and the inactivation of protease inhibitors. These proteolytic interactions enable functional cross-talk between proteases and have been well established in proteolytic cascades. In addition, far-reaching interactions beyond classically defined protease cascades hav...
Article
Full-text available
The adult human skin contains a vast number of T cells that are essential for skin homeostasis and pathogen defense. T cells are first observed in the skin at the early stages of gestation, however, our understanding of their contribution to early immunity has been limited by their low abundance and lack of comprehensive methodologies for their ass...
Article
Full-text available
T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we identified a naive T cell population expressing αβ and γδ T cell receptors (TCRs) that was enriched i...
Article
Full-text available
Atopic dermatitis (AD) typically starts in infancy or early childhood, showing spontaneous remission in a subset of patients, while others develop lifelong disease. Despite an increased understanding of AD, factors guiding its natural course are only insufficiently elucidated. We thus performed suction blistering in skin of adult patients with stab...
Article
Therapeutic options for autoimmune diseases typically consist of broad and targeted immunosuppressive agents. However, sustained clinical benefit is rarely achieved, as the disease phenotype usually returns after cessation of treatment. To better understand tissue-resident immune memory in human disease, we investigated patients with atopic dermati...
Article
Full-text available
Glioblastoma might have widespread effects on the neural organization and cognitive function, and even focal lesions may be associated with distributed functional alterations. However, functional changes do not necessarily follow obvious anatomical patterns and the current understanding of this interrelation is limited. In this study, we used resti...
Article
Full-text available
Background: Cardiac fibroblasts (CFs) have a central role in the ventricular remodeling process associated with different types of fibrosis. Recent studies have shown that fibroblasts do not respond homogeneously to heart injury. Because of the limited set of bona fide fibroblast markers, a proper characterization of fibroblast population heteroge...
Article
Full-text available
Background: Deep learning has emerged as a versatile approach for predicting complex biological phenomena. However, its utility for biological discovery has so far been limited, given that generic deep neural networks provide little insight into the biological mechanisms that underlie a successful prediction. Here we demonstrate deep learning on b...
Conference Paper
Langerhans cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. It occupies a characteristic hybrid position between cancer and inflammatory disease, which makes it an attractive model for studying cancer development. Constitutive activation of the ERK signaling pathway is a common feature of LCH, but its pathogenesis remai...
Article
Full-text available
The mammalian immune system implements a remarkably effective set of mechanisms for fighting pathogens1. Its main components are haematopoietic immune cells, including myeloid cells that control innate immunity, and lymphoid cells that constitute adaptive immunity2. However, immune functions are not unique to haematopoietic cells, and many other ce...
Conference Paper
Full-text available
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, but its complex pathogenesis is still only partly understood. To comprehensively characterize AD on both transcriptomic and proteomic levels in humans, we used skin suction blistering, a painless and non-scarring procedure that can simultaneously sample skin cells and inte...
Article
Full-text available
Background: Single-cell RNA-seq (scRNA-seq) is emerging as a powerful tool to dissect cell-specific effects of drug treatment in complex tissues. This application requires high levels of precision, robustness, and quantitative accuracy-beyond those achievable with existing methods for mainly qualitative single-cell analysis. Here, we establish the...
Article
Purpose Spirometric lung function is one of the central clinical parameters to assess allograft function after lung transplantation (LTX). Reduction in FEV1 can be the result of infections, rejections episodes and most importantly development of CLAD. Currently, there is no means to predict short-term changes in lung function after LTX. Methods Br...
Article
Purpose The pulmonary microbiome after lung transplantation has recently come into the focus of research. Especially, host-microbiome interactions are thought to be an important factor in graft-related immunological processes. In lung transplantation, temporal changes of the pulmonary microbiome have not yet been elucidated. Methods In a total coh...
Article
Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, but its complex pathogenesis is only insufficiently understood, resulting in still limited treatment options. Objective: We sought to characterize AD on both transcriptomic and proteomic levels in humans. Methods: We used skin suction blistering, a painles...
Article
Full-text available
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib provides effective treatment for patients with chronic lymphocytic leukemia (CLL), despite extensive heterogeneity in this disease. To define the underlining regulatory dynamics, we analyze high-resolution time courses of ibrutinib treatment in patients with CLL, combining immune-phenotyping, sin...
Preprint
Deep learning has emerged as a powerful methodology for predicting a variety of complex biological phenomena. However, its utility for biological discovery has so far been limited, given that generic deep neural networks provide little insight into the biological mechanisms that underlie a successful prediction. Here we demonstrate deep learning on...
Article
Full-text available
Langerhans cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. It occupies a hybrid position between cancers and inflammatory diseases, which makes it an attractive model for studying cancer development. To explore the molecular mechanisms underlying the pathophysiology of LCH and its characteristic clinical heterogeneity,...
Preprint
Cardiac fibroblasts have a central role during the ventricular remodeling process associated with different types of cardiac injury. Recent studies have shown that fibroblasts do not respond homogeneously to heart damage, suggesting that the adult myocardium may contain specialized fibroblast subgroups with specific functions. Due to the limited se...
Preprint
Full-text available
Chronic lymphocytic leukemia (CLL) is a genetically, epigenetically, and clinically heterogeneous disease. Despite this heterogeneity, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib provides effective treatment for the vast majority of CLL patients. To define the underlining regulatory program, we analyzed high-resolution time courses of ibru...
Article
Full-text available
Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of DNA methylation in matched primary and recurring glioblastoma tumors, using data from a highly annotated clinical cohort that was select...
Article
Full-text available
Controlled macrophage differentiation and activation in the initiation and resolution of inflammation is crucial for averting progression to chronic inflammatory and autoimmune diseases. Here we show a negative feedback mechanism for proinflammatory IFN-γ activation of macrophages driven by macrophage-associated matrix metalloproteinase 12 (MMP12)....
Preprint
Full-text available
Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of the DNA methylation dynamics in matched primary and recurring glioblastoma tumors, based on a national population registry and a compreh...
Article
Full-text available
Protein interactions shape proteome function and thus biology. Identification of protein interactions is a major goal in molecular biology, but biochemical methods, although improving, remain limited in coverage and accuracy. Whereas computational predictions can guide biochemical experiments, low validation rates of predictions remain a major limi...
Article
Full-text available
Protein–protein interaction networks (interactomes) define the functionality of all biological systems. In apoptosis, proteolysis by caspases is thought to initiate disassembly of protein complexes and cell death. Here we used a quantitative proteomics approach, protein correlation profiling (PCP), to explore changes in cytoplasmic and mitochondria...
Article
Full-text available
Deregulated cathepsin proteolysis occurs across numerous cancers, but in vivo substrates mediating tumorigenesis remain ill-defined. Applying 8-plex iTRAQ terminal amine isotopic labeling of substrates (TAILS), a systems-level N-terminome degradomics approach, we identified cathepsin B, H, L, S, and Z in vivo substrates and cleavage sites with the...
Article
Full-text available
Many diseases are associated with endoplasmic reticulum (ER) stress, which results from an accumulation of misfolded proteins. This triggers an adaptive response called the unfolded protein response (UPR), and prolonged exposure to ER stress leads to cell death. Caspases are reported to play a critical role in ER stress-induced cell death but the u...
Article
Full-text available
Almost all regulatory processes in biology ultimately lead to or originate from modifications of protein function. However, it is unclear to which extent each mechanism of regulation actually affects proteins and thus phenotypes. We assessed the extent of N-terminal protein truncation in a global analysis of N-terminomics data and find that most pr...
Article
Full-text available
Proteases, and specifically metalloproteinases, have been linked to the loss of platelet function during storage before transfusion, but the underlying mechanisms remain unknown. We used a dedicated N-terminomics technique, iTRAQ terminal amine isotopic labeling of substrates (TAILS), to characterize the human platelet N-terminome, proteome, and po...
Article
Full-text available
The knowledgebase TopFIND is an analysis platform focussed on protein termini, their origin, modification and hence their role on protein structure and function. Here, we present a major update to TopFIND, version 3, which includes a 70% increase in the underlying data to now cover a 90 696 proteins, 165 044 N-termini, 130 182 C-termini, 14 382 cle...
Article
Full-text available
Proteolytic processing is an irreversible posttranslational modification affecting a large portion of the proteome. Protease-cleaved mediators frequently exhibit altered activity, and biological pathways are often regulated by proteolytic processing. Many of these mechanisms have not been appreciated as being protease-dependent, and the potential i...

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