Isabelle Salles-Crawley graduated from Université Blaise Pascal in Clermont-Ferrand, France in 1995 with a MSc in Molecular and Plant Biology, and obtained her PhD in Microbiology from the University of Oklahoma in 2001. Her first post-doctoral position was at the University of Oklahoma in Professor Jimmy Ballard's laboratory, exploring the pathogenesis of bacterial toxins. In 2004, she joined the Thrombosis and Haemostasis group with Professors Hans Deckmyn and Karen Vanhoorelbeke at KU-Leuven, Belgium. She joined the Centre for Haematology at Imperial College London in 2009 where she received an Intermediate Basic Science Research Fellowship to investigate the role of BAMBI in thrombus formation. Isabelle secured additional funding from the British Heart Foundation to continue her research at Imperial College and became an Advanced Research Fellow in 2020. She joined the MCSI (Vascular Biology Section) at St George’s University of London in September 2021.

Over the years she has developed many in vitro and in vivo models of thrombosis and published over 35 papers in peer-reviewed scientific journals. She recently joined the editorial board of Research and Practice in Thrombosis and Haemostasis.

She is a committee member of the British Society for Thrombosis and Haemostasis, a member of the International Society on Thrombosis and Haemostasis and the Platelet Society. She has joined the British Heart Foundation project grant committee in 2023.

Isabelle Salles-Crawley’s research consists in understanding the molecular mechanisms associated with blood clotting. Upon vascular injury, platelets can roll and interact with collagen-bound VWF at the site of injury and together with the activation of the coagulation form a haemostatic plug to seal the wound. Dysregulation of this finely tune system can lead to bleeding (e.g. platelet disorders) or thrombosis and associated complications (e.g. deep vein thrombosis, stroke, myocardial infarction).

Her lab is particularly interested how cells interact to form a thrombus on the vessel wall and therefore a lot of her research involves ex vivo and intravital imaging of thrombi. Over the years, she demonstrated a role in thrombus formation and stability for a transmembrane protein - BAMBI - identified through transcriptomics, and more recently started to explore the roles of some anticoagulant proteins (thrombomodulin and TFPI) using the laser-induced thrombosis model. She has also been investigating the role of BAMBI in a model of inflammation – atherosclerosis. The data so far suggest that BAMBI deficiency is protective against plaque formation through improved cholesterol and triglyceride metabolism. The physiological ligand of BAMBI is still unclear, and its identification will be the focus of the next grant application as it will be invaluable to identify in what cells/tissue BAMBI exert its different roles.

We have recently uncovered a novel mechanism by which VWF-primed platelets signal to activate one of the main platelet receptors aIIbβ3 to recruit neutrophils and T-cells under flow. We believe this novel interaction between primed platelets and neutrophils –capable of triggering NETosis – or T-cells is important in several pathological conditions including deep vein thrombosis and stroke. To further evaluate the physiological importance of platelet priming in vivo, we have generated a new knockin mouse (GpIbα^Δsig/Δsig) with a truncated GPIbα intracellular tail (via CRISPR/Cas9 technology) with blunted VWF-GPIbα platelet signalling. This mouse model will be invaluable to further explore the pathophysiological relevance of the binding of primed platelets via aIIbβ3 to the neutrophil receptor SLC44A2 - that has recently been identified as a susceptibility locus for venous thrombosis.

During the characterisation of the GpIbα^Δsig/Δsig mice, we have highlighted not only that the intracellular tail of GPIbα is important for VWF-GPIbα signalling but also plays a role in an important platelet signalling pathway involving GPVI. The exact mechanism by which this GPIbα/GPVI cross talk is occurring is currently the focus of the Salles-Crawley’s lab.

Selected publications

1. Petri A,* Sasikumar P,* Badia Folgado P, Jones D, Xu Y, Ahnström J,*^$ Salles-Crawley II*^$ and Crawley JTB^*$: TFPIa anticoagulant function is highly dependent upon protein S in vivo. Science Adv. 2024 Feb 2;10(5):eadk5836.
2. Gierula M, Noakes VM, Salles-Crawley II, Crawley JTB and Ahnström, 2023: The TFPIα C-terminal tail is essential for the synergistic enhancement of TFPIα mediated FXa inhibition by protein S and FV-short. J Thromb. Haem. Dec; 21(12):3568-3580.
3. Mereweather L,* Constantinescu-Bercu A,* Crawley JTB, and Salles-Crawley II^$, 2023:“Platelet-Neutrophil Crosstalk in Thrombosis.” J. Mol. Sci., Volume 24, Issue 2, 1266.
4. Malik A, Sayed AA, Han PP, Tan M, Watt E, Constantinescu-Bercu A, Cocker ATH, Khoder A, Thorley E, Teklemichael A, Ding Y, Saputil R, Hart A, Zhang H, Mitchell WA, Imami N, Crawley JTB, Salles-Crawley II, Bussel JB, Zehnder JL, Adams S, Zhang BM^$*, and Cooper N^$*: The role of polyfunctional cytotoxic T cell clones in immune thrombocytopenia. Blood (in press).
5. Constantinescu-Bercu A, Wang YA, Woollard KJ, Mangin P, Vanhoorelbeke K, Crawley JTB and Salles-Crawley II^$, 2022: The GPIbα intracellular tail - role in transducing VWF- and Collagen/GPVI-mediated signaling. Haematologica Apr 1;107(4):933-946.
6. Huang Y, Gu B, Salles-Crawley II, Taylor KA, Yu L, Ren J, Liu X, Emerson M, Longstaff C, Hughes AD, Thom SA, Xu XY and Chen R, 2021: Fibrinogen-mimicking, multi-arm nanovesicles with thrombus-specific delivery of tissue plasminogen activator for targeted thrombolytic therapy. Science Adv. Jun 2;7(23):eabf9033.
7. Constantinescu-Bercu A, Grassi L, Frontini M, Salles-Crawley II*^$, Woollard KJ*^$ and Crawley JTB*^$, 2020: Novel platelet-neutrophil interaction between activated αIIbβ3 and SLC44A2 mediates NETosis under flow. Elife Apr 21;9:e53353.
8. Peghaire C, Dufton NP, Lang M, Salles-Crawley II, Ahnström J, Kalna V, Raimondi C, Pericleous C, Inuabasi L, Mason JC, Birdsey GM and Randi A.M., 2019: Low shear stress-dependent regulation of thrombosis in the microvasculature orchestrated by the transcription factor ERG. Nature Commun. 1;10(1):5014.
9. Crawley JTB, Zalli A, Monkman JH, Lane DA, Ahnström J and Salles-Crawley II^$, 2019: Defective fibrin deposition and thrombus stability in Bambi^-/- mice are mediated by elevated anticoagulant function. doi: 10.1111/jth.14593 J Thromb. Haem. 17(11):1935-1949.
10. Teraz-Orosz A, Cooper N, Crawley JTB and Salles-Crawley II^$ 2018: Detection of anti-platelet antibodies in immune thrombocytopenia by flow cytometry. Br J Haematol. 2018 Mar 13.
11. Thijs T., Broos K., Soenen S., Vandelbulcke A., Vanhoorelbeke K., Deckmyn H.* and Salles-Crawley I.I.,* ^$ 2015: Artificial miRNAs to successfully knockdown platelet glycoprotein Ibα: a tool for platelet gene silencing. Plos one, 10(7):e0132899.
12. Salles-Crawley I.I.^$, Monkman J.H., Ahnstrӧm J., Lane D.A. and Crawley J.T.B, 2014: Vessel wall BAMBI contributes to hemostasis and thrombus stability, Blood, 123(18):2873-81.
13. Salles I.I.^$, Broos K., Fontayne A., Szanto T., Ruan C., Nurden A.T., Vanhoorelbeke K., and Deckmyn H., 2010: Development Of A High-throughput ELISA Assay To Study Platelet Function. Thrombosis and Haemostasis, 104:392-401.
14. Salles I.I.^$, Thijs T., Brunaud C., De Meyer S.F., Thys J., Vanhoorelbeke K, and Deckmyn H., 2009: Human platelets produced in NOD/SCID mice upon transplantation of human cord blood CD34⁺ cells are functionally active in an ex vivo flow model of thrombosis. Blood,114(24):5044-51.
15. O’Connor M.N.*, Salles I.I.*, Cvejic A., Watkins N.A., Walker A., Garner S.F., Jones C.I., Macaulay I.C., Steward S., Zwaginga J-J, Bray S., Dudbridge F., de Bono B., Goodall A.H., Deckmyn H., Stemple D.L., and Ouwehand W.H., 2009: Functional genomics in zebrafish permits rapid characterization of novel platelet membrane proteins. Blood, 113(19): 4754-62.
16. Salles I.I., De Meyer S., Vanhoorelbeke K., Iserbyt B., Feys H. and Deckmyn H., 2008: Inherited genetic traits affecting platelet function. Blood Reviews, 22(3): 155-172.
17. Salles I.I.*, Voth D.E.*, Ward S.C., Averette K.M., Tweten R.K., Bradley K.B, and Ballard J.D., 2006: Cytotoxic activity of Bacillus anthracis protective antigen for a macrophage cell line overexpressing ANTRX1. Cellular Microbiology, 8(8): 1272-81.
18. Salles I.I., Tucker A.E., Voth D. E., and Ballard J.D., 2003: Toxin-induced resistance in Bacillus anthracis lethal-toxin treated macrophages. Proc Nat Acad Sci USA, 100 (21), 12426-31.

Recent collaborations

• Prof Jim Crawley, Dpt of Immunology and Inflammation, Imperial College London, UK
• Dr Josefin Ahnström, Dpt of Immunology and Inflammation, Imperial College London, UK
• Dr Rongjun Chen, Dpt of Chemical Engineering, Imperial College London, UK
• Dr Nichola Cooper, Dpt of Immunology and Inflammation, Imperial College London, UK
• Prof Iain Greenwood, MCS, SGUL, UK.
• Prof Andreas Greinacher, University of Greifswald, Germany
• Prof Mike Levin, Dpt of Infectious Disease, Imperial College London, UK
• Dr Pierre Mangin, INSERM, EFS-Alsace, France
• Dr Tom Nightingale, Queen Mary University of London, UK
• Prof Anna Randi, National Heart & Lung Institute, Imperial College London, UK
• Prof Karen Vanhoorelbeke, Laboratory of thrombosis Research, KU Leuven, Belgium