Prof Thomas Iskratsch
Professor of Cardiovascular Mechanobiology and Bioengineering
CPM Industrial Engagement and Partnerships Lead,
CPM Theme lead for Cardiovascular Models
School of Engineering and Materials Science
Queen Mary University of London
Queen Mary University of London
Research
Cardiovascular Mechanobiology, Mechanosensing, Cardiovascular Disease, Micro-/Nanopatterning, 3D models
Interests
Cells in the cardiovascular system react to the changing mechanical stimuli. This affects their behaviour and can trigger cardiovascular disease onset and progression. We are studying cellular mechanosensing in cardiomyocytes and vascular smooth muscle cells, in 2D and 3D in vitro models and using tools to apply or measure forces (AFM, nanoindentation, nanopillars, pressure stimulation), as well as super-resolution or high content imaging and automated image analysis. This allows us to dissect cellular pathways of mechanosignalling and identify novel therapeutic targets, or to develop improved drug testing platforms.Publications
Publications of specific relevance to Predictive in vitro Models2024
Swiatlowska P, Iskratsch T and Shanahan C (2024). Mechano-epigenetic regulation of vascular smooth muscle cell phenotype in atherosclerosis. Elsevier Atherosclerosis vol. 395, 10.1016/j.atherosclerosis.2024.118395Swiatlowska P, Tipping W, Marhuenda E, Severi P, Fomin V, Yang Z, Xiao Q, Graham D, Shanahan C and Iskratsch T (2024). Hypertensive Pressure Mechanosensing Alone Triggers Lipid Droplet Accumulation and Transdifferentiation of Vascular Smooth Muscle Cells to Foam Cells (Adv. Sci. 9/2024). Wiley Advanced Science vol. 11, (9) 10.1002/advs.202470050Fromager B, Cambedouzou J, Marhuenda E, Iskratsch T, Pinault M, Bakalara N and Cornu D (2024). Tunable electrospun scaffolds of polyacrylonitrile loaded with carbon nanotubes: from synthesis to biological applications. Wiley Chembiochem 10.1002/cbic.202300768Faleeva M, Ahmad S, Theofilatos K, Lynham S, Watson G, Whitehead M, Marhuenda E, Iskratsch T, Cox S and Shanahan CM (2024). Sox9 Accelerates Vascular Ageing by Regulating Extracellular Matrix Composition and Stiffness. American Heart Association Circulation Research 10.1161/CIRCRESAHA.123.3233652023
Iskratsch T, Swiatlowska P, Tipping W, Marhuenda E, Severi P, Fomin V, Yang Z, Xiao Q, Graham D and Shanahan C (2023). Hypertensive pressure mechanosensing alone triggers lipid droplet accumulation and
transdifferentiation of vascular smooth muscle cells to foam cells. Wiley Open Access Advanced Science 10.1002/advs.202308686Ross JA, Arcos-Villacis N, Battey E, Boogerd C, Orellana CA, Marhuenda E, Swiatlowska P, Hodzic D, Prin F, Mohun T, Catibog N, Tapia O, Gerace L, Iskratsch T, Shah AM and Stroud MJ (2023). Lem2 is essential for cardiac development by maintaining nuclear integrity. Oxford University Press Cardiovascular Research vol. 119, (11) 2074-2088. 10.1093/cvr/cvad061Swiatlowska P and Iskratsch T (2023). Cardiovascular Mechano-Epigenetics: Force-Dependent Regulation of Histone Modifications and Gene Regulation. Springer Cardiovascular Drugs and Therapy 10.1007/s10557-022-07422-zBattey E, Ross JA, Hoang A, Wilson DGS, Han Y, Levy Y, Pollock RD, Kalakoutis M, Pugh JN, Close GL, Ellison‐Hughes GM, Lazarus NR, Iskratsch T, Harridge SDR, Ochala J and Stroud MJ (2023). Myonuclear alterations associated with exercise are independent of age in humans. Wiley The Journal of Physiology 10.1113/jp2841282022
Jacques R, Zhou B, Marhuenda E, Gorecki J, Das A, Iskratsch T and Krause S (2022). Photoelectrochemical imaging of single cardiomyocytes and monitoring of their action potentials through contact force manipulation of organoids. Elsevier Biosensors and Bioelectronics 10.1016/j.bios.2022.115024Iskratsch T, Hawkes W, Marhuenda E, Reynolds P, O'Neill C, PANDEY P, Wilson D, FREELEY M, HUANG D, Junquiang H, Gondarenko S, Hone J, Gadegaard N and Palma M (2022). Regulation of Cardiomyocyte Adhesion and
Mechanosignalling Through Distinct Nanoscale Behaviour of
Integrin Ligands Mimicking Healthy or Fibrotic ECM. The Royal Society Philosophical Transactions of The Royal Society B: Biological Sciences 10.1098/rstb.2022.0021Iskratsch T, Wilson D and Tinker A (2022). The role of the dystrophin glycoprotein complex in muscle cell mechanotransduction. Nature Research Communications Biology 10.1038/s42003-022-03980-ySwiatlowska P, Sit BHM, Zhen F, Marhuenda E, Xanthis I, Zingaro S, Ward M, Zhou X, Xiao Q, Shanahan C, Jones G, Yu C-H and Iskratsch T (2022). Pressure and stiffness sensing together regulate vascular smooth muscle cell phenotype switching. American Association For The Advancement of Science Science Advances 10.1126/sciadv.abm3471Wilson DGS and Iskratsch T (2022). Factoring in the force: A novel role for eIF6. The Journal of Cell Biology vol. 221, (2) 10.1083/jcb.2022010022021
Swiatlowska P and Iskratsch T (2021). 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. Springer (Part of Springer Nature) Biophysical Reviews vol. 13, (5) 575-577. 10.1007/s12551-021-00842-5Swiatlowska P and Iskratsch T (2021). Tools for studying and modulating (cardiac muscle) cell mechanics and mechanosensing across the scales. Springer Nature Biophysical Reviews vol. 13, (5) 611-623. 10.1007/s12551-021-00837-2Swiatlowska 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”. Springer Nature Biophysical Reviews vol. 13, (3) 307-308. 10.1007/s12551-021-00800-1Marhuenda 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/s13046-021-01925-72020
(2020). Cell scientist to watch – Thomas Iskratsch. The Company of Biologists Journal of Cell Science vol. 133, (15) 10.1242/jcs.2515952019
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.2019.119683Xanthis I and Iskratsch T (2019). Lamin-A Mechano-Protects the Heart. Developmental Cell 10.1016/j.devcel.2019.05.041Pedrosa 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-18-3934Sit B, Gutmann D and Iskratsch T (2019). Costameres, dense plaques and podosomes: the cell matrix adhesions in cardiovascular mechanosensing. Springer Nature Journal of Muscle Research and Cell Motility vol. 40, (2) 197-209. 10.1007/s10974-019-09529-7Hawkes W, Huang D, Reynolds P, Hammond L, Ward M, Gadegaard N, Marshall JF, Iskratch T and Palma M (2019). Probing the nanoscale organisation and multivalency of cell surface receptors: DNA origami nanoarrays for cellular studies with single-molecule control. Royal Society of Chemistry (Rsc) Faraday Discussions 10.1039/c9fd00023bWard M and Iskratsch T (2019). Mix and (mis-)match – The mechanosensing machinery in the changing environment of the developing, healthy adult and diseased heart. Elsevier Biochimica Et Biophysica Acta (Bba) - Molecular Cell Research vol. 1867, (3) 10.1016/j.bbamcr.2019.01.0172018
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/s41598-018-35948-6Pandey 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.2017.12.0242017
Lee NM, Erisken C, Iskratsch T, Sheetz M, Levine WN and Lu HH (2017). Polymer fiber-based models of connective tissue repair and healing. Biomaterials vol. 112, 303-312. 10.1016/j.biomaterials.2016.10.0132016
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.2016.61Meacci G, Wolfenson H, Liu S, Stachowiak MR, Iskratsch T, Mathur A, Ghassemi S, Gauthier N, Tabdanov E, Lohner J, Gondarenko A, Chander AC, Roca-Cusachs P, O'Shaughnessy B, Hone J and Sheetz MP (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.E16-02-01072015
Wolfenson H, Meacci G, Liu S, Stachowiak MR, Iskratsch T, Ghassemi S, Roca-Cusachs P, O'Shaughnessy B, Hone J and Sheetz MP (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/ncb3277Tabdanov 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/c5ib00032g2014
Wolfenson H, Iskratsch T and Sheetz MP (2014). Early Events in Cell Spreading as a Model for Quantitative Analysis of Biomechanical Events. Elsevier Biophysical Journal vol. 107, (11) 2508-2514. 10.1016/j.bpj.2014.10.041Iskratsch 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/nrm3903Dwyer 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.22984Zhang X, Moore SW, Iskratsch T and Sheetz MP (2014). N-WASP-directed actin polymerization activates Cas phosphorylation and lamellipodium spreading. The Company of Biologists Journal of Cell Science vol. 127, (7) 1394-1405. 10.1242/jcs.1346922013
Iskratsch T, Yu C-H, 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. Elsevier Developmental Cell vol. 27, (5) 545-559. 10.1016/j.devcel.2013.11.0032012
Lynch CD, Lazar AM, Iskratsch T, Zhang X and Sheetz MP (2012). Endoplasmic spreading requires coalescence of vimentin intermediate filaments at force-bearing adhesions. American Society For Cell Biology (Ascb) Molecular Biology of The Cell vol. 24, (1) 21-30. 10.1091/mbc.e12-05-0377Iskratsch T, Reijntjes S, Dwyer J, Toselli P, Dégano IR, Dominguez I and Ehler E (2012). Two distinct phosphorylation events govern the function of muscle FHOD3. Springer Nature Cellular and Molecular Life Sciences vol. 70, (5) 893-908. 10.1007/s00018-012-1154-7Roca-Cusachs P, Iskratsch T and Sheetz MP (2012). Finding the weakest link – exploring integrin-mediated mechanical molecular pathways. The Company of Biologists Journal of Cell Science vol. 125, (13) 3025-3038. 10.1242/jcs.0957942011
Dwyer J, Iskratsch T and Ehler E (2011). Actin in striated muscle: recent insights into assembly and maintenance. Springer Nature Biophysical Reviews vol. 4, (1) 17-25. 10.1007/s12551-011-0062-7Iskratsch T and Ehler E (2011). Formin-g muscle cytoarchitecture. Taylor & Francis Bioarchitecture vol. 1, (2) 66-68. 10.4161/bioa.1.2.154672010
Iskratsch T, Lange S, Dwyer J, Kho AL, Remedios CD and Ehler E (2010). Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance. Rockefeller University Press The Journal of General Physiology vol. 137, (1) i1-i1. 10.1085/jgp1371oia1Iskratsch 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. Rockefeller University Press Journal of Cell Biology vol. 191, (6) 1159-1172. 10.1083/jcb.2010050602009
Herbst R, Iskratsch T, Unger E and Bittner RE (2009). Aberrant development of neuromuscular junctions in glycosylation-defective Largemyd mice. Elsevier Neuromuscular Disorders vol. 19, (5) 366-378. 10.1016/j.nmd.2009.02.011Gutternigg M, Rendić D, Voglauer R, Iskratsch T and Wilson IBH (2009). Mammalian cells contain a second nucleocytoplasmic hexosaminidase. Portland Press Biochemical Journal vol. 419, (1) 83-90. 10.1042/bj200816302008
Iskratsch T, Braun A, Paschinger K and Wilson IBH (2008). Specificity analysis of lectins and antibodies using remodeled glycoproteins. Elsevier Analytical Biochemistry vol. 386, (2) 133-146. 10.1016/j.ab.2008.12.005Grants
Grants of specific relevance to Predictive in vitro Models
Artery-on-a-Chip (S&E flexible match-funded PhD studentship)Iskratsch T
£103,372 Novo Nordisk Foundation (Denmark) (01-01-2024 - 31-12-2026)
Talin dependent mechanical imprinting as driver for cardiac disease progressionIskratsch T
£718,167 British Heart Foundation (01-01-2024 - 31-12-2026)
Nanobioarrays to screen for modulators of mechanosensing in heart failureIskratsch T and Kotalakshminaraasimulu N
Engineering and Physical Sciences Research Council (30-09-2022 - 30-03-2026)
The role of novel mechanosensitive complex in cardiomyocyte pathophysiologyIskratsch T
£285,532 British Heart Foundation (01-10-2024 - 30-09-2024)
Coupling optical tweezers with light microscopy to unravel the mechanobiology of diseaseGarcia-Manyes S, Iskratsch T, Elosegui Artola A, Tiago C, Gentleman E, Parsons M, Booth P, Blackburn B and PARACUELLOS TORRECILLA P
£707,768 Medical Research Council (01-08-2023 - 29-02-2024)
The regulation of mechanosensing in healthy and atherosclerotic vascular smooth muscle cellsSwiatlowska P and Iskratsch T
£238,020 British Heart Foundation (01-12-2020 - 30-11-2023)
3D Photoelectrochemical imaging in porous light-addressable structuresKrause SK, Zhou B and Iskratsch T
£202,249 Engineering and Physical Sciences Research Council (01-02-2021 - 31-10-2022)
Investigating the cardiomyocyte rigidity sensing mechanism with micro patterned surfaces and nanopillarsIskratsch T
£490,544 Biotechnology and Biological Sciences Research Council (01-02-2019 - 31-01-2022)
Actin polymerization during myofibrillogenesis and its regulation by mechanosensingIskratsch T
USD92,000 American Heart Association (01-01-2013 - 31-12-2014)