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Lamins are nucleoskeletal proteins forming a scaffold structure at the nuclear envelope of all metazoan cells, termed the nuclear lamina. They determine mechanical properties of the nucleus and regulate spatial chromatin organization by anchoring heterochromatin to the nuclear periphery. Over 400 mutations in the LMNA gene have been identified that cause various rare diseases, including muscular dystrophy, cardiomyopathy, lipodystrophy and premature aging. We try to understand the molecular functions of lamins in mechanosignaling and chromatin regulation at mechanistic level. This will allow us to elucidate the roles of lamins in adult stem cell regulation and tissue homeostasis and to discover lamin-linked defects during aging. We also aim at a better understanding of molecular disease mechanisms in lamin-linked diseases to foster the development of novel therapeutic and diagnostic tools for patient treatment.
We study lamin functions in health and disease using a curiosity driven research strategy. We apply a wide range of molecular biological and biochemical approaches, including high-end light microscopy, gene targeting and protein-protein and protein-DNA interaction analyses as well as genome- and proteome-wide techniques. These studies provide mechanistic insight into lamin-mediated pathways and their dynamic regulation during cell proliferation and differentiation. We also generate and use cellular and animal models to understand the downstream consequences of lamin dysfunction in aging and disease and to identify the contributions of impaired lamin functions to pathologies in lamin-linked diseases at cellular, tissue and organismal level.
Roland Foisner received his PhD (Dr. techn.) in Biotechnology at the TU Vienna, Austria. He moved to the USA in 1991 working as postdoctoral fellow at Scripps, La Jolla, CA, and started his own lab in 1993 at the (Medical) University Vienna. He became Full Professor in 2002 and served as Deputy Head of MFPL from 2007 to 2017. Roland Foisner is founder and Editor-in-Chief of the journal Nucleus.
LMNA mutations cause progeria, a severe disease with features of accelerating aging in multiple tissues, including cardiovascular disease and atherosclerosis. We show that vascular endothelial cells in progeria cannot cope with blood flow-mediated shear stress and upregulate pro-fibrotic mechanosignaling pathways, causing fibrosis, vessel stiffening and heart problems.
While the attachment of heterochromatin to the peripheral lamina is well known, we found that, in addition, lamins bind to open, active chromatin regions inside the nucleus. This novel and dynamic lamin-chromatin interaction increases chromatin accessibility and regulates epigenetic pathways thereby contributing to differentiation-specific gene expression.
In addition to their peripheral localization, lamins are found in a dynamic pool in the nuclear interior. We identified the lamin-binding protein,LAP2alpha,as a cell cycle-dependent regulator of the dynamic lamin pool. Depletion of LAP2alpha leads to loss of nucleoplasmic lamins and impairment of adult stem cell regulation.
Impaired cell proliferation is a hallmark of premature aging disease and normal aging. We found that this is accompanied by loss of the nucleoplasmic lamin-LAP2alpha complexes. Re-expression of LAP2alpha in aged cells is sufficient to rescue proliferation defects, likely by inducing collagen expression. Our studies reveal potential new treatment strategies for age-linked diseases.
Endothelial progerin expression causes cardiovascular pathology through an impaired mechanoresponse.
Osmanagic-Myers, Selma; Kiss, Attila; Manakanatas, Christina; Hamza, Ouafa; Sedlmayer, Franziska; Szabo, Petra L; Fischer, Irmgard; Fichtinger, Petra; Podesser, Bruno K; Eriksson, Maria; Foisner, Roland
Lamins in the nuclear interior - life outside the lamina.
Naetar, Nana; Ferraioli, Simona; Foisner, Roland
A-type lamins bind both hetero- and euchromatin, the latter being regulated by lamina-associated polypeptide 2 alpha.
Gesson, Kevin; Rescheneder, Philipp; Skoruppa, Michael P; von Haeseler, Arndt; Dechat, Thomas; Foisner, Roland
Proliferation of progeria cells is enhanced by lamina-associated polypeptide 2α (LAP2α) through expression of extracellular matrix proteins
Vidak, Sandra, Kubben, Nard, Dechat, Thomas and Roland Foisner
Loss of LAP2 alpha delays satellite cell differentiation and affects postnatal fiber-type determination.
Gotic, Ivana; Schmidt, Wolfgang M; Biadasiewicz, Katarzyna; Leschnik, Michael; Spilka, Rita; Braun, Juliane; Stewart, Colin L; Foisner, Roland
Project title: “Chromatin organization by lamina-independent lamins" (P 26492-B20)
Contribution of endothelial cell dysfunction to cardiovascular disease in progeria (PRF 2016-64)
The Group Foisner is a member of the special Doctoral Program "Signaling Mechanisms in Cellular Homeostasis" reviewed and funded by the Austrian Research Fund FWF.
Systematic identification and functional characterization of transcriptional regulators
The mineralosphere as microhabitat for microbe, mineral and organic matter interaction in soils
Activation and regulation of plant immunity by secreted signaling peptides
Transcription start site selection is environmentally controlled to diversify the proteome in eukaryotes
How evolutionary interplay between sexes can help us define phenotypes and develop drugs
Mining for protein-protein interactions with AlphaFold: Lessons from Genome Maintenance
Title to be announced
The magical Martian Methane mystery and other stories about life on Mars
Probing life at the nanoscale - one molecule at a time
The Underworld of Deep-Sea Hydrothermal Vents
Epigenetic regulation of germline development
Sister chromatid cohesion is mediated by individual cohesin complexes
Origin and evolution of a defensive symbiosis in tortoise leaf beetles
Capturing conformational transitions in the ubiquitin conjugation cascade
18th Microsymposium on RNA Biology
The „Microsymposium on RNA Biology“ is an international conference that brings together young scientists, junior and senior group leaders, and company representatives from all over the world to present and discuss their latest findings in the exciting field of small RNAs and beyond. The Microsymposium was founded in 2005 and has established itself as the major small RNA meeting in Europe. It is organized by the four research institutions IMBA, IMP, GMI and the Max Perutz Labs as well as by the RNA community of the Vienna BioCenter.
Transformation Reactions of Organic Contaminants and Oxygen: From Field Sites to Reaction Mechanisms
Title to be announced
Multiscale plant bioimaging using advanced microscopy
Parthenogenesis, cryptobiosis, and the survival in extreme environmental conditions
Evading ageing: Mitochondrial and proteostatic adaptations in oocytes
Ubiquitin & Friends Symposium 2024
The Ubiquitin & Friends Symposium is an annual international meeting taking place in the beautiful capital of Austria, aiming to bring together scholars from various fields studying ubiquitin/Ubl biology and protein degradation in a personal, family-like atmosphere, as suggested by the name.
Genomes in Rhodnius prolixus symbiotic system
Stem cells, immune evasion and metastasis in colorectal cancer
The evolution and development of mollusc shells
Unraveling the Complexity of Crossover Regulation in C. elegans
Dynamics of 3D Genome Structure and Function
How superworms can help to solve our plastic waste crisis
New players in an old pathway: biology of methanogens of the TACK superphylum
Shaping morphogen gradients: from molecules to tissues and back
Studying stressed cells by in situ structural biology
Exploring Microbial Resilience: Unravelling Escherichia coliand#x27;s Stress Response at the Level of Protein Synthesis
Deep homology and deep diversity: Evolving genetic toolkits for making and sensing light
The evolution of cell type identity and tissue microecology at the fetal-maternal interface
The unanticipated roles of PICIs and phages in bacterial evolution
Origin and diversification of gut-derived organs in chordates
Job's Dilemma for the Genome: Why Bad Things Happen to Good Chromosomes
Connections between carbon and nitrogen cycling in the ocean
Understanding how the DNA-loop-extruding protein complex Condensin folds a chromatinized genome into mitotic chromosomes
From Roads to Rivers? Occurrence and environmental fate of tire and road wear particles and of tire-related chemicals
Striking physiology and cell biology of (marine) environmental microorganisms
Mechanisms controlling maintenance of cohesin dependent loops
Title to be announced