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Materials Research Institute

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Dr Thomas Iskratsch

Thomas Iskratsch

Reader in Cardiovascular Mechanobiology and Bioengineering

School of Engineering and Materials Science
219A, Engineering, Mile End
+44 (0)20 7882 3674

www.sems.qmul.ac.uk/staff/t.iskratsch

Research

cardiomyocyte rigidity sensing mechanism, micro patterned surfaces and nanopil, cardiac remodelling, Mechano-regulation of myofibril formation

Research Interests

The role of mechanical signals in the cardiovascular system

The cellular microenvironment is defined by both chemical and physical/mechanical parameters. Recent data inidicated that mechanical signals, such as extracellular matrix  rigidity contribute to guide cell migration, growth or differentiation during development or in disease.

Our research aims at understanding how mechanical forces regulate cell behavior especially in the cardiovascular system, including the formation and maintenance of the contractile myofibrils in cardiomyocytes during heart development or in cardiac disease, or the determination of vascular smooth muscle cell phenotypes (contractile or synthetic). To answer these questions we use techniques, such as nanopillar arrays, micro and nano-patterning,  magnetic tweezers or molecular Förster resonance energy transfer (FRET) protein activity and tension sensors.

Publications of specific relevance to Materials Research

Publications

2021

  • Swiatlowska P and Iskratsch T (2021). Announcing the call for the Special Issue on “Cardiovascular mechanobiology—a special issue to look at the state of the art and the newest insights into the role of mechanical forces in cardiovascular development, physiology, and disease”. Biophysical Reviews  vol. 13, (3) 307-308. 10.1007/s12551-021-00800-1
  • Marhuenda E, Fabre C, Zhang C, Martin-Fernandez M, Iskratsch T, Saleh A, Bauchet L, Cambedouzou J, Hugnot JP, Duffau H, Dennis JW, Cornu D and Bakalara N (2021). Glioma stem cells invasive phenotype at optimal stiffness is driven by MGAT5 dependent mechanosensing. Journal of Experimental and Clinical Cancer Research  vol. 40, (1) 10.1186/s13046-021-01925-7

2020

  • Iskratsch T (2020). Cell scientist to watch. Journal of Cell Science  vol. 133, (15) 10.1242/JCS.251595
  • Ward M and Iskratsch T (2020). Mix and (mis-)match – The mechanosensing machinery in the changing environment of the developing, healthy adult and diseased heart. Biochimica Et Biophysica Acta - Molecular Cell Research  vol. 1867, (3) 10.1016/j.bbamcr.2019.01.017

2019

  • Di Cio S, Iskratsch T, Connelly JT and Gautrot JE (2019). Contractile myosin rings and cofilin-mediated actin disassembly orchestrate ECM nanotopography sensing. Elsevier  Biomaterials  vol. 232, 10.1016/j.biomaterials.2019.119683
  • Xanthis I and Iskratsch T (2019). Lamin-A Mechano-Protects the Heart. Developmental Cell  10.1016/j.devcel.2019.05.041
  • Pedrosa A-R, BODRUG N, Gomez-Escudero J, Carter EP, Reynolds LE, Georgiou PN, Fernandez I, Lees DM, Kostourou V, Alexopoulou AN, Batista S, Tavora B, Serrels B, Parsons M, Iskratsch T and Hodivala-Dilke K (2019). Tumour angiogenesis is differentially regulated by endothelial cell Focal Adhesion Kinase tyrosine-397 and -861 phosphorylation. American Association For Cancer Research  Cancer Research  10.1158/0008-5472.CAN-18-3934
  • Sit B, Gutmann D and Iskratsch T (2019). Costameres, dense plaques and podosomes: the cell matrix adhesions in cardiovascular mechanosensing. Journal of Muscle Research and Cell Motility  vol. 40, (2) 197-209. 10.1007/s10974-019-09529-7

2018

  • Ciuba K, Hawkes W, Tojkander S, Kogan K, Engel U, ISKRATSCH T and Lappalainen P (2018). Calponin-3 is critical for coordinated contractility of actin stress fibers. Nature Publishing Group  Scientific Reports  10.1038/s41598-018-35948-6
  • Pandey P, Hawkes W, Hu J, Megone WV, Gautrot J, Anilkumar N, Zhang M, Hirvonen L, Cox S, Ehler E, Hone J, Sheetz M and Iskratsch T (2018). Cardiomyocytes Sense Matrix Rigidity through a Combination of Muscle and Non-muscle Myosin Contractions. Dev Cell  vol. 44, (3) 326-336.e3. 10.1016/j.devcel.2017.12.024

2017

2016

  • Santos LC, Blair DA, Kumari S, Cammer M, Iskratsch T, Herbin O, Alexandropoulos K, Dustin ML and Sheetz MP (2016). Actin polymerization-dependent activation of Cas-L promotes immunological synapse stability. Immunol Cell Biol  vol. 94, (10) 981-993. 10.1038/icb.2016.61
  • (2016). α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions. Mol Biol Cell  vol. 27, (22) 3471-3479. 10.1091/mbc.E16-02-0107

2015

  • (2015). Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices. Nat Cell Biol  vol. 18, (1) 33-42. 10.1038/ncb3277
  • Tabdanov E, Gondarenko S, Kumari S, Liapis A, Dustin ML, Sheetz MP, Kam LC and Iskratsch T (2015). Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells. Integr Biol (Camb)  vol. 7, (10) 1272-1284. 10.1039/c5ib00032g

2014

  • Wolfenson H, Iskratsch T and Sheetz MP (2014). Early events in cell spreading as a model for quantitative analysis of biomechanical events. Biophysical Journal  vol. 107, (11) 2508-2514. 10.1016/j.bpj.2014.10.041
  • Iskratsch T, Wolfenson H and Sheetz MP (2014). Appreciating force and shape—the rise of mechanotransduction in cell biology. Nature Reviews. Molecular Cell Biology  vol. 15, (12) 825-833. 10.1038/nrm3903
  • Dwyer J, Pluess M, Iskratsch T, Dos Remedios CG and Ehler E (2014). The formin FHOD1 in cardiomyocytes. Anat Rec (Hoboken)  vol. 297, (9) 1560-1570. 10.1002/ar.22984
  • Zhang X, Moore SW, Iskratsch T and Sheetz MP (2014). N-WASP-directed actin polymerization activates Cas phosphorylation and lamellipodium spreading. Journal of Cell Science  vol. 127, (7) 1394-1405. 10.1242/jcs.134692

2013

  • Iskratsch T, Yu CH, Mathur A, Liu S, Stévenin V, Dwyer J, Hone J, Ehler E and Sheetz M (2013). FHOD1 is needed for directed forces and adhesion maturation during cell spreading and migration. Developmental Cell  vol. 27, (5) 545-559. 10.1016/j.devcel.2013.11.003
  • Iskratsch T, Reijntjes S, Dwyer J, Toselli P, Dégano IR, Dominguez I and Ehler E (2013). Two distinct phosphorylation events govern the function of muscle FHOD3. Cellular and Molecular Life Sciences  vol. 70, (5) 893-908. 10.1007/s00018-012-1154-7
  • Lynch CD, Lazar AM, Iskratsch T, Zhang X and Sheetz MP (2013). Endoplasmic spreading requires coalescence of vimentin intermediate filaments at force-bearing adhesions. Molecular Biology of The Cell  vol. 24, (1) 21-30. 10.1091/mbc.E12-05-0377

2012

  • Roca-Cusachs P, Iskratsch T and Sheetz MP (2012). Finding the weakest link-exploring integrin-mediated mechanical molecular pathways. Journal of Cell Science  vol. 125, (13) 3025-3038. 10.1242/jcs.095794
  • Dwyer J, Iskratsch T and Ehler E (2012). Actin in striated muscle: Recent insights into assembly and maintenance. Biophysical Reviews  vol. 4, (1) 17-25. 10.1007/s12551-011-0062-7

2011

2010

  • Iskratsch T, Lange S, Dwyer J, Kho AL, Dos Remedios C and Ehler E (2010). Formin follows function: A muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance. Journal of Cell Biology  vol. 191, (6) 1159-1172. 10.1083/jcb.201005060

2009

  • Herbst R, Iskratsch T, Unger E and Bittner RE (2009). Aberrant development of neuromuscular junctions in glycosylation-defective Largemyd mice. Neuromuscular Disorders  vol. 19, (5) 366-378. 10.1016/j.nmd.2009.02.011
  • Gutternigg M, Rendi¿ D, Voglauer R, Iskratsch T and Wilson IBH (2009). Mammalian cells contain a second nucleocytoplasmic Hexosaminidase. Biochemical Journal  vol. 419, (1) 83-90. 10.1042/BJ20081630
  • Iskratsch T, Braun A, Paschinger K and Wilson IBH (2009). Specificity analysis of lectins and antibodies using remodeled glycoproteins. Analytical Biochemistry  vol. 386, (2) 133-146. 10.1016/j.ab.2008.12.005

Grants of specific relevance to Materials Research

Grants

  • The regulation of mechanosensing in healthy and atherosclerotic vascular smooth muscle cells
    Swiatlowska P and Iskratsch T
    £238,020 British Heart Foundation (01-12-2020 - 30-11-2023)
  • Investigating the cardiomyocyte rigidity sensing mechanism with micro patterned surfaces and nanopillars
    Iskratsch T
    £490,544 Biotechnology and Biological Sciences Research Council (01-02-2019 - 31-01-2022)
    Abstract