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SIRT2 Inhibition by AGK2 Promotes Perinuclear Cytoskeletal Organisation and Reduces Invasiveness of MDA-MB-231 Triple-Negative Breast Cancer Cells in Confined In Vitro Models (2024)
Journal Article
Jessop, E., Young, N., Garcia-Del-Valle, B., Crusher, J. T., Obara, B., & Karakesisoglou, I. (2024). SIRT2 Inhibition by AGK2 Promotes Perinuclear Cytoskeletal Organisation and Reduces Invasiveness of MDA-MB-231 Triple-Negative Breast Cancer Cells in Confined In Vitro Models. Cells, 13(23), Article 2023. https://doi.org/10.3390/cells13232023

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype characterised by the absence of targetable hormone receptors and increased metastatic rates. As nuclear softening strongly contributes to TNBC’s enhanced metastatic cap... Read More about SIRT2 Inhibition by AGK2 Promotes Perinuclear Cytoskeletal Organisation and Reduces Invasiveness of MDA-MB-231 Triple-Negative Breast Cancer Cells in Confined In Vitro Models.

Inhibition of PDIs Downregulates Core LINC Complex Proteins, Promoting the Invasiveness of MDA-MB-231 Breast Cancer Cells in Confined Spaces In Vitro (2024)
Journal Article
Young, N., Gui, Z., Mustafa, S., Papa, K., Jessop, E., Ruddell, E., …Karakesisoglou, I. (2024). Inhibition of PDIs Downregulates Core LINC Complex Proteins, Promoting the Invasiveness of MDA-MB-231 Breast Cancer Cells in Confined Spaces In Vitro. Cells, 13(11), Article 906. https://doi.org/10.3390/cells13110906

Eukaryotic cells tether the nucleoskeleton to the cytoskeleton via a conserved molecular bridge, called the LINC complex. The core of the LINC complex comprises SUN-domain and KASH-domain proteins that directly associate within the nuclear envelope l... Read More about Inhibition of PDIs Downregulates Core LINC Complex Proteins, Promoting the Invasiveness of MDA-MB-231 Breast Cancer Cells in Confined Spaces In Vitro.

An Intronic Heterozygous SYNE2 Splice Site Mutation: A Rare Cause for Myalgia and hyperCKemia? (2024)
Journal Article
Paulus, T., Young, N., Jessop, E., Berwanger, C., Clemen, C. S., Schröder, R., Ploski, R., Hagel, C., Hellenbroich, Y., Moser, A., & Karakesisoglou, I. (2024). An Intronic Heterozygous SYNE2 Splice Site Mutation: A Rare Cause for Myalgia and hyperCKemia?. Muscles, 3(1), 100-109. https://doi.org/10.3390/muscles3010010

SYNE2 mutations have been associated with skeletal and cardiac muscle diseases, including Emery-Dreifuss muscular dystrophy (EDMD). Here, we present a 70-year-old male patient with muscle pain and elevated serum creatine kinase levels in whom whole-e... Read More about An Intronic Heterozygous SYNE2 Splice Site Mutation: A Rare Cause for Myalgia and hyperCKemia?.

Quantitative morphometric analysis of intrinsic and extrinsic skin ageing in individuals with Fitzpatrick skin types II–III (2023)
Journal Article
Costello, L., Goncalves, K., De Los Santos Gomez, P., Simpson, A., Maltman, V., Ritchie, P., Tasseff, R., Isfort, R., Dicolandrea, T., Wei, X., Määttä, A., Karakesisoglou, I., Markiewicz, E., Bascom, C. C., & Przyborski, S. (2023). Quantitative morphometric analysis of intrinsic and extrinsic skin ageing in individuals with Fitzpatrick skin types II–III. Experimental Dermatology, 32(5), 620-631. https://doi.org/10.1111/exd.14754

Skin ageing is an intricate physiological process affected by intrinsic and extrinsic factors. There is a demand to understand how the skin changes with age and photoexposure in individuals with Fitzpatrick skin types I-III due to accelerated photoag... Read More about Quantitative morphometric analysis of intrinsic and extrinsic skin ageing in individuals with Fitzpatrick skin types II–III.

Biallelic SYNE2 Missense Mutations Leading to Nesprin-2 Giant Hypo-Expression Are Associated with Intellectual Disability and Autism (2021)
Journal Article
Young, N., Asif, M., Jackson, M., Fernández-Mayoralas, D. M., de la Peña, M. J., Calleja-Pérez, B., Álvarez, S., Hunter-Featherstone, E., Noegel, A. A., Höhne, W., Nürnberg, P., Obara, B., Hussain, M. S., Karakesisoglou, I., & Fernández-Jaén, A. (2021). Biallelic SYNE2 Missense Mutations Leading to Nesprin-2 Giant Hypo-Expression Are Associated with Intellectual Disability and Autism. Genes, 12(9), Article 1294. https://doi.org/10.3390/genes12091294

Autism spectrum disorder (ASD) is a group of neurological and developmental disabilities characterised by clinical and genetic heterogeneity. The current study aimed to expand ASD genotyping by investigating potential associations with SYNE2 mutation... Read More about Biallelic SYNE2 Missense Mutations Leading to Nesprin-2 Giant Hypo-Expression Are Associated with Intellectual Disability and Autism.

Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro (2021)
Journal Article
Hunter-Featherstone, E., Young, N., Chamberlain, K., Cubillas, P., Hulette, B., Wei, X., Tiesman, J. P., Bascom, C. C., Benham, A. M., Goldberg, M. W., Saretzki, G., & Karakesisoglou, I. (2021). Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro. Cells, 10(5), https://doi.org/10.3390/cells10051177

Mechanotransduction is defined as the ability of cells to sense mechanical stimuli from their surroundings and translate them into biochemical signals. Epidermal keratinocytes respond to mechanical cues by altering their proliferation, migration, and... Read More about Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro.

Bioengineering the Microanatomy of Human Skin (2019)
Journal Article
Roger, M., Fullard, N., Costello, L., Bradbury, S., Markiewicz, E., O'Reilly, S., Darling, N., Ritchie, P., Määttä, A., Karakesisoglou, I., Nelson, G., von Zglinicki, T., Dicolandrea, T., Isfort, R., Bascom, C., & Przyborski, S. (2019). Bioengineering the Microanatomy of Human Skin. Journal of Anatomy, 234(4), 438-455. https://doi.org/10.1111/joa.12942

Recreating the structure of human tissues in the laboratory is valuable for fundamental research, testing interventions, and reducing the use of animals. Critical to the use of such technology is the ability to produce tissue models that accurately r... Read More about Bioengineering the Microanatomy of Human Skin.

p63 transcription factor regulates nuclear shape and expression of nuclear envelope-associated genes in epidermal keratinocytes (2017)
Journal Article
Rapisarda, V., Malashchuk, I., Asamaowei, I. E., Poterlowicz, K., Fessing, M. Y., Sharov, A. A., …Mardaryev, A. (2017). p63 transcription factor regulates nuclear shape and expression of nuclear envelope-associated genes in epidermal keratinocytes. Journal of Investigative Dermatology, 137(10), 2157-2167. https://doi.org/10.1016/j.jid.2017.05.013

The maintenance of a proper nuclear architecture and 3D organization of the genes, enhancer elements and transcription machinery plays an essential role in tissue development and regeneration. Here we show that in the developing skin, epidermal proge... Read More about p63 transcription factor regulates nuclear shape and expression of nuclear envelope-associated genes in epidermal keratinocytes.

Nesprins in health and disease. (2013)
Journal Article
Cartwright, S., & Karakesisoglou, I. (2014). Nesprins in health and disease. Seminars in Cell and Developmental Biology, 29, 169-179. https://doi.org/10.1016/j.semcdb.2013.12.010

LINC (Linker of Nucleoskeleton and Cytoskeleton) complex is an evolutionary conserved structure that spans the entire nuclear envelope (NE), and integrates the nuclear interior with the cytoskeleton, in order to support a diverse array of fundamental... Read More about Nesprins in health and disease..

Nesprin interchain associations control nuclear size. (2012)
Journal Article
Lu, W., Schneider, M., Neumann, S., Jaeger, V., Taranum, S., Munck, M., …Karakesisoglou, I. (2012). Nesprin interchain associations control nuclear size. Cellular and Molecular Life Sciences, 69(20), 3493-3509. https://doi.org/10.1007/s00018-012-1034-1

Nesprins-1/-2/-3/-4 are nuclear envelope proteins, which connect nuclei to the cytoskeleton. The largest nesprin-1/-2 isoforms (termed giant) tether F-actin through their N-terminal actin binding domain (ABD). Nesprin-3, however, lacks an ABD and ass... Read More about Nesprin interchain associations control nuclear size..

Cytotoxic T lymphocyte effector function is independent of nucleus–centrosome dissociation (2012)
Journal Article
Lui-Roberts, W., Stinchcombe, J., Ritter, A., Akhmanova, A., Karakesisoglou, I., & Griffiths, G. (2012). Cytotoxic T lymphocyte effector function is independent of nucleus–centrosome dissociation. European Journal of Immunology, 42(8), 2132-2141. https://doi.org/10.1002/eji.201242525

Cytotoxic T lymphocytes (CTLs) kill tumorigenic and virally infected cells by targeted secretion of lytic granule contents. The precise point at which secretion occurs is directed by the centrosome docking at the immunological synapse (IS). The centr... Read More about Cytotoxic T lymphocyte effector function is independent of nucleus–centrosome dissociation.

Cytoskeletal interactions at the nuclear envelope mediated by Nesprins (2012)
Journal Article
Taranum, S., Sur, I., Muller, R., Lu, W., Rashmi, R., Munch, M., …Noegel, A. (2012). Cytoskeletal interactions at the nuclear envelope mediated by Nesprins. International Journal of Cell Biology, 2012, Article 736524. https://doi.org/10.1155/2012/736524

Nesprin-1 is a giant tail-anchored nuclear envelope protein composed of an N-terminal F-actin binding domain, a long linker region formed by multiple spectrin repeats and a C-terminal transmembrane domain. Based on this structure, it connects the nuc... Read More about Cytoskeletal interactions at the nuclear envelope mediated by Nesprins.

Induction of a massive endoplasmic reticulum and perinuclear space expansion by expression of lamin B receptor mutants and the related sterol reductases TM7SF2 and DHCR7. (2010)
Journal Article
Zwerger, M., Kolb, T., Richter, K., Karakesisoglou, I., & Herrmann, H. (2010). Induction of a massive endoplasmic reticulum and perinuclear space expansion by expression of lamin B receptor mutants and the related sterol reductases TM7SF2 and DHCR7. Molecular Biology of the Cell, 21(2), 354-368. https://doi.org/10.1091/mbc.e09-08-0739

The LINC-less granulocyte nucleus (2009)
Journal Article
Olins, A., Hoang, T., Zwerger, M., Herrmann, H., Zentgraf, H., Noegel, A., …Olins, D. (2009). The LINC-less granulocyte nucleus. European Journal of Cell Biology, 88(4), 203-14

The major blood granulocyte (neutrophil) is rapidly recruited to sites of bacterial and fungal infections. It is a highly malleable cell, allowing it to squeeze out of blood vessels and migrate through tight tissue spaces. The human granulocyte nucle... Read More about The LINC-less granulocyte nucleus.

Sun1 forms immobile macromolecular assemblies at the nuclear envelope (2008)
Journal Article
Lu, W., Gotzmann, J., Sironi, L., Jaeger, V., Schneider, M., Luke, Y., …Karakesisoglou, I. (2008). Sun1 forms immobile macromolecular assemblies at the nuclear envelope. Biochimica et biophysica acta, 1783(12), 2415-26

SUN-domain proteins form a novel and conserved family of inner nuclear membrane (INM) proteins, which establish physical connections between the nucleoplasm and the cytoskeleton. In the current study, we provide evidence that within the nuclear envel... Read More about Sun1 forms immobile macromolecular assemblies at the nuclear envelope.

Nesprin-2 Giant (NUANCE) maintains nuclear envelope architecture and composition in skin (2008)
Journal Article
Luke, Y., Zaim, H., Karakesisoglou, I., Jaeger, V., Sellin, L., Lu, W., …Noegel, A. (2008). Nesprin-2 Giant (NUANCE) maintains nuclear envelope architecture and composition in skin. Journal of Cell Science, 121(11), 1887-1898. https://doi.org/10.1242/jcs.019075

Giant isoforms, encoded by Nesprin-1 (Syne1) and Nesprin-2 (Syne2), are multifunctional actin-binding and nuclear-envelope-associated proteins belonging to the spectrin superfamily. Here, we investigate the function of Nesprin-2 Giant (NUANCE) in ski... Read More about Nesprin-2 Giant (NUANCE) maintains nuclear envelope architecture and composition in skin.