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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.
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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.
Roland Foisner
Group Leader +43 1 4277 61680
Room: 3.113
Raquel Silva
PhD Student +43 1 4277 61673
Room: 3.108
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, Foisner Roland
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.