Dr Alex Bye
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0118 378 5504
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Lecturer in Pharmacology
Areas of interest
18 million people die from cardiovascular diseases (CVDs) every year, accounting for approximately one-third of all global deaths. This includes deaths from heart attacks (myocardial infarction) and stroke, which involve blood clots forming within blood vessels that block blood flow to the heart of brain. Small cells in the blood called platelets play a central role in forming these clots. One of the best ways to prevent heart attacks and strokes is to reduce the ability of platelets to form clots using antiplatelet medications. These drugs are effective for many, but a minority of patients will suffer a cardiovascular event while on antiplatelet therapy. Another limitation of antiplatelet drugs is increased risk of haemorrhage, including catastrophic forms of bleeding such as intracranial haemorrhage (haemorrhagic stroke). In my research, I work with patients that are at risk of these negative outcomes to better understand why and work towards better treatments.
My interests include:
- Drug-induced platelet dysfunction
- Biomarkers of platelet hyper-reactivity
- Platelet signalling
- Spatiotemporal signalling in megakaryocytes
- Kinase inhibitors as antiplatelet drugs
- von Willebrand Factor in thrombosis and haemostasis
Publications
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Mitchell, J.
,
Dunster, J.
,
Kriek, N.
,
Unsworth, A.
,
Sage, T.
,
Mohammed, Y.
,
De Simone, I.
,
Taylor, K.
,
Bye, A.
ORCID: 0000-0002-2061-2253
,
Ólafsson, G.
,
Brunton, M.
,
Mark, S.
,
Dymott, L.
,
Whyte, A.
,
Ruparelia, N.
,
Mckenna, C.
,
Gibbins, J.
ORCID: 0000-0002-0372-5352
,
Jones, C.
ORCID: 0000-0001-7537-1509
(2023)
The rate of platelet activation determines thrombus size and structure at arterial shear.
Journal of Thrombosis and Haemostasis
ISSN:
1538-7836
|
doi:
https://dx.doi.org/10.1016/j.jtha.2023.03.044
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Bye, A.
ORCID: 0000-0002-2061-2253
,
Kriek, N.
,
Sage, T.
,
Rawlings, S.
,
Prodger, C.
,
Kesavan, M.
,
Lees, C.
,
Booth, S.
,
Cowen, L.
,
Shefferd, K.
,
Desborough, M.
,
Gibbins, J.
ORCID: 0000-0002-0372-5352
,
Eyre, T.
(2022)
Pirtobrutinib results in reversible platelet dysfunction compared to ibrutinib and acalabrutinib.
Haematologica
ISSN:
1592-8721
|
doi:
https://dx.doi.org/10.3324/haematol.2022.281402
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Kriek, N.
,
Nock, S.
,
Sage, T.
,
Khalifa, B.
,
Bye, A.
ORCID: 0000-0002-2061-2253
,
Mitchell, J.
,
Thomson, S.
,
McLaughlin, M.
,
Jones, S.
,
Gibbins, J.
ORCID: 0000-0002-0372-5352
,
Unsworth, A.
ORCID: 0000-0003-3809-5984
(2022)
Cucurbitacins elicit anti-platelet activity via perturbation of the cytoskeleton and integrin function.
Thrombosis and Haemostasis
, 122
(7).
pp.
1115-1129.
ISSN:
0340-6245
|
doi:
https://dx.doi.org/10.1055/a-1788-5322
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Alatawi, K.
,
Ravishankar, D.
,
Patra, P.
,
Bye, A.
,
Stainer, A.
,
Patel, K.
,
Widera, D.
ORCID: 0000-0003-1686-130X
,
Vaiyapuri, S.
ORCID: 0000-0002-6006-6517
(2021)
1,8-cineole affects agonists-induced platelet activation, thrombus formation and haemostasis.
Cells
, 10
(10).
ISSN:
2073-4409
|
doi:
https://dx.doi.org/10.3390/cells10102616
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Bye, A.
,
Hoepel, W.
,
Mitchell, J.
,
Jegouic, S.
,
Loureiro, S.
,
Sage, T.
,
Vidarsson, G.
,
Nouta, J.
,
Wuhrer, M.
,
de Taeye, S.
,
van Gils, M.
,
Kriek, N.
,
Cooper, N.
,
Jones, I.
ORCID: 0000-0002-7738-2516
,
den Dunnen, J.
,
Gibbins, J.
ORCID: 0000-0002-0372-5352
(2021)
Aberrant glycosylation of anti-SARS-CoV-2 spike IgG is a pro-thrombotic stimulus for platelets.
Blood
, 138
(16).
pp.
1481-1489.
ISSN:
0006-4971
|
doi:
https://dx.doi.org/10.1182/blood.2021011871
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Dunster, J.
,
Bye, A.
,
Kriek, N.
,
Sage, T.
,
Mitchell, J.
,
Kempster, C.
,
Batista, J.
,
KcKinney, H.
,
Thomas, P.
,
Jones, C.
ORCID: 0000-0001-7537-1509
,
Downes, K.
,
Unsworth, A.
,
Gibbins, J.
ORCID: 0000-0002-0372-5352
(2021)
Multi-parameter phenotyping of platelet reactivity for stratification of human cohorts.
Blood Advances
, 5
(20).
pp.
4017-4030.
ISSN:
2473-9529
|
doi:
https://dx.doi.org/10.1182/bloodadvances.2020003261
- Sahli, K. , Flora, G. , Sasikumar, P. , Maghrabi, A. , Holbrook, L. , AlOuda, S. , Elgheznawy, A. , Sage, T. , Stainer, A. , Adiyaman, R. , AboHassan, M. , Crescente, M. , Kriek, N. , Vaiyapuri, S. , Bye, A. , Unsworth, A. , Jones, C. , McGuffin, L. , Gibbins, J. (2021) Structural, functional and mechanistic insights uncover the fundamental role of orphan connexin-62 in platelets. Blood , 137 (6). pp. 830-843. ISSN: 0006-4971 | doi: https://dx.doi.org/10.1182/blood.2019004575
- Unsworth, A. , Bye, A. , Sage, T. , Gaspar, R. , Eaton, N. , Drew, C. , Stainer, A. , Kriek, N. , Volberding, P. , Hutchinson, J. , Riley, R. , Jones, S. , Mundell, S. , Cui, W. , Falet, H. , Gibbins, J. (2021) Anti-platelet properties of Pim kinase inhibition is mediated through disruption of thromboxane A2 receptor signalling. Haematologica , 106 (7). ISSN: 1592-8721 | doi: https://dx.doi.org/10.3324/haematol.2019.223529
- Bye, A. , Gibbins, J. , Mahaut-Smith, M. (2020) Ca2+ waves coordinate purinergic receptor–evoked integrin activation and polarization. Science Signaling , 13 (615). ISSN: 1937-9145 | doi: https://dx.doi.org/10.1126/scisignal.aav7354
- Dunster, J. , Unsworth, A. , Bye, A. , Haining, E. , Sowa, M. , Di, Y. , Sage, T. , Pallini, C. , Pike, J. , Hardy, A. , Nieswandt, B. , García, Á. , Watson, S. , Poulter, N. , Gibbins, J. , Pollitt, A. (2020) Interspecies differences in protein expression do not impact the spatiotemporal regulation of glycoprotein VI mediated activation. Journal of Thrombosis and Haemostasis , 18 (2). pp. 485-496. ISSN: 1538-7836 | doi: https://dx.doi.org/10.1111/jth.14673
- Stainer, A. , Sasikumar, P. , Bye, A. , Unsworth, A. , Holbrook, L. , Tindall, M. , Lovegrove, J. , Gibbins, J. (2019) The metabolites of the dietary flavonoid quercetin possess potent antithrombotic activity, and interact with aspirin to enhance antiplatelet effects. TH Open , 3 (3). pp. e244-e258. ISSN: 2512-9465 | doi: https://dx.doi.org/10.1055/s-0039-1694028
- Stainer, A. , Sasikumar, P. , Bye, A. , Unsworth, A. , Holbrook, L. , Tindall, M. , Lovegrove, J. , Gibbins, J. (2019) Quercetin and its methylated metabolites possess anti-thrombotic properties that interact with aspirin to enhance its anti-platelet effects. TH Open , 3 (3). pp. e244-e258. ISSN: 2512-9465 | doi: https://dx.doi.org/10.1055/s-0039-1694028
- Unsworth, A. , Bye, A. , Kriek, N. , Sage, T. , Osborne, A. , Donaghy, D. , Gibbins, J. (2019) Cobimetinib and trametinib inhibit platelet MEK but do not cause platelet dysfunction. Platelets , 30 (6). pp. 762-772. ISSN: 0953-7104 | doi: https://dx.doi.org/10.1080/09537104.2018.1514107
- Bye, A. , Ilkan, Z. , Unsworth, A. , Jones, C. (2018) Immobilization of nonactivated unfixed platelets for real-time single-cell analysis. In: Gibbins, J. and Mahaut-Smith, M. , (eds.) Platelets and Megakaryocytes (Volume 4, Advanced Protocols and Perspectives). Methods in Molecular Biology , 1812. Springer Protocols pp. 1-11. ISBN: 9781493985845
- Bye, A. , Unsworth, A. , Gibbins, J. (2018) Screening and high-throughput platelet assays. In: Gibbins, J. and Mahaut-Smith, M. , (eds.) Platelets and Megakaryocytes: Volume 4, Advanced Protocols and Perspectives. , 1812. Methods in molecular biology (Clifton, N.J.) , 1812 pp. 81-94. ISSN: 1940-6029 ISBN: 9781493985845 | doi: https://dx.doi.org/10.1007/978-1-4939-8585-2_5
- Bye, A. and Gibbins, J. (2018) Move along, nothing to see here: Btk inhibitors stop platelets sticking to plaques. Journal of Thrombosis and Haemostasis , 16 (8). pp. 1461-1463. ISSN: 1538-7933 | doi: https://dx.doi.org/10.1111/jth.14201
- Sasikumar, P. , AlOuda, K. , Kaiser, W. , Holbrook, L. , Kriek, N. , Unsworth, A. , Bye, A. , Sage, T. , Ushioda, R. , Nagata, K. , Farndale, R. , Gibbins, J. (2018) The chaperone protein HSP47: a platelet collagen binding protein that contributes to thrombosis and haemostasis. Journal of Thrombosis and Haemostasis , 16 (5). pp. 946-959. ISSN: 1538-7933 | doi: https://dx.doi.org/10.1111/jth.13998
- Bye, A. , Unsworth, A. , Desborough, M. , Hildyard, C. , Appleby, N. , Bruce, D. , Kriek, N. , Nock, S. , Sage, T. , Hughes, C. , Gibbins, J. (2017) Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib. Blood Advances , 1 (26). pp. 2610-2623. ISSN: 2473-9529 | doi: https://dx.doi.org/10.1182/bloodadvances.2017011999
- Unsworth, A. , Bye, A. , Tannetta, D. , Desborough, M. , Kriek, N. , Sage, T. , Allan, H. , Crescente, M. , Yaqoob, P. , Warner, T. , Jones, C. , Gibbins, J. (2017) Farnesoid X receptor and liver X receptor ligands initiate formation of coated platelets. Arteriosclerosis, thrombosis, and vascular biology , 37 (8). pp. 1482-1493. ISSN: 1524-4636 | doi: https://dx.doi.org/10.1161/ATVBAHA.117.309135
- Unsworth, A. , Flora, G. , Sasikumar, P. , Bye, A. , Sage, T. , Kriek, N. , Crescente, M. , Gibbins, J. (2017) RXR ligands negatively regulate thrombosis and hemostasis. Arteriosclerosis Thrombosis and Vascular Biology , 37 (5). pp. 812-822. ISSN: 1524-4636 | doi: https://dx.doi.org/10.1161/ATVBAHA.117.309207
- Unsworth, A. , Kriek, N. , Bye, A. , Naran, K. , Sage, T. , Flora, G. , Gibbins, J. (2017) PPARγ agonists negatively regulate αIIbβ3 integrin outside-in signalling and platelet function through upregulation of protein kinase A activity. Journal of Thrombosis and Haemostasis , 15 (2). pp. 356-369. ISSN: 1538-7933 | doi: https://dx.doi.org/10.1111/jth.13578
- Moraes, L. , Unsworth, A. , Vaiyapuri, S. , Ali, M. , Sasikumar, P. , Sage, T. , Flora, G. , Bye, A. , Kriek, N. , Dorchies, E. , Molendi-Coste, O. , Dombrowicz, D. , Staels, B. , Bishop-Bailey, D. , Gibbins, J. (2016) Farnesoid X Receptor and its ligands inhibit the function of platelets. Arteriosclerosis Thrombosis and Vascular Biology , 36 (12). pp. 2324-2333. ISSN: 1524-4636 | doi: https://dx.doi.org/10.1161/ATVBAHA.116.308093
- Bye, A. , Unsworth, A. , Gibbins, J. (2016) Platelet signaling: a complex interplay between inhibitory and activatory networks. Journal of Thrombosis and Haemostasis , 14 (5). pp. 918-930. ISSN: 1538-7933 | doi: https://dx.doi.org/10.1111/jth.13302
- Bye, A. , Unsworth, A. , Vaiyapuri, S. , Stainer, A. , Fry, M. , Gibbins, J. (2015) Ibrutinib inhibits platelet integrin αIIbβ3 outside-in signaling and thrombus stability but not adhesion to collagen. Arteriosclerosis Thrombosis and Vascular Biology , 35 (11). pp. 2326-2335. ISSN: 1524-4636 | doi: https://dx.doi.org/10.1161/ATVBAHA.115.306130