Dr Thomas Iskratsch

Thomas Iskratsch
PhD, Dipl.-Ing.

Reader in Cardiovascular Mechanobiology and Bioengineering
CPM Industrial Engagement lead and Director of PREMMIR Centre for Doctoral Training

School of Engineering and Materials Science
Queen Mary University of London
+44 (0)20 7882 3674
www.sems.qmul.ac.uk/staff/t.iskratsch

Research

Cardiovascular Mechanobiology, Mechanosensing, Cardiovascular Disease, Micro-/Nanopatterning, 3D models

Underpinning Bioengineering, Cardiovascular 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 Models

2023

Ross 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. Cardiovascular Research  vol. 119, (11) 2074-2088. 10.1093/cvr/cvad061
Swiatlowska 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-z
Battey 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. Journal of Physiology  10.1113/JP284128

2022

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.2022.115024
Iskratsch 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.2022.0021
Iskratsch 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-y
Swiatlowska 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.abm3471
Wilson 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.202201002

2021

Swiatlowska P and Iskratsch T (2021). Tools for studying and modulating (cardiac muscle) cell mechanics and mechanosensing across the scales. Biophysical Reviews  vol. 13, (5) 611-623. 10.1007/s12551-021-00837-2
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/s12551-021-00842-5
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
Hawkes 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/c9fd00023b

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

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.2016.10.013

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
Meacci 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.E16-02-0107

2015

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/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

Iskratsch T and Ehler E (2011). Formin-g muscle cytoarchitecture. Bioarchitecture  vol. 1, (2) 66-68. 10.4161/bioa.1.2.15467

2010

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/jgp1371oia1
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, Rendić 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

Grants of specific relevance to Predictive in vitro Models
Nanobioarrays to screen for modulators of mechanosensing in heart failure
Iskratsch T and Kotalakshminaraasimulu NK
Engineering and Physical Sciences Research Council (19-09-2022 - 30-03-2026)
Summary
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)

3D Photoelectrochemical imaging in porous light-addressable structures
Krause 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 nanopillars
Iskratsch T
£490,544 Biotechnology and Biological Sciences Research Council (01-02-2019 - 31-01-2022)
Summary
Actin polymerization during myofibrillogenesis and its regulation by mechanosensing
Iskratsch T
USD92,000 American Heart Association (01-01-2013 - 31-12-2014)
Summary