Dr Alexandra Mazharian PhD

Dr Alexandra Mazharian

Institute of Cardiovascular Sciences
British Heart Foundation Intermediate Research Fellow

Contact details

+44 (0)121 415 8678
+44 (0)121 415 8817
Institute of Cardiovascular Sciences
College of Medical and Dental Sciences
Institute of Biomedical Research
University of Birmingham
B15 2TT

Alexandra Mazharian is a British Heart Foundation Intermediate Basic Science Research Fellow working at the Institute of Cardiovascular Sciences.  The primary objective of Alexandra’s research is to elucidate novel signalling events regulating megakaryocyte development and platelet production in health and disease.


  • PhD Biology of Blood Cells , Université Denis-Diderot Paris VII, France
  • MSc Biology of Blood Cells , Université Denis-Diderot Paris VII, France
  • BSc(Hons), Life Sciences, Université de Créteil Paris XII, France


Dr Alexandra Mazharian obtained her PhD in 2007 in Blood cell Biology from the University Denis-Diderot, Paris 7, investigating the role of MAPKs in platelet activation.  Her PhD thesis was under the supervision of Dr Marijke Bryckaert at the Cardiovascular Research centre of Lariboisiere in Paris.  She then undertook postdoctoral training in the laboratory of Prof Steve Watson at the University of Birmingham, UK, investigating novel signalling mechanisms regulating megakaryocyte development, migration and platelet production.  She also investigated the molecular basis of thrombocytopenia and haemorrhaging caused by the Src family kinase inhibitor Dasatinib, used in the treatment of chronic myeloid leukaemia.  In 2011, Dr Mazharian joined the laboratory of Prof Yotis Senis as a postdoctoral fellow, at the University of Birmingham, UK, investigating the functional roles of the novel platelet ITIM-containing receptor G6b-B and the structurally-related protein-tyrosine phosphatases Shp1 and Shp2 in megakaryopoiesis.  In 2013, Alexandra was awarded a British Heart Foundation Project Grant investigating the regulation of megakaryocyte and platelet hyperactivity and prothrombotic activity by the ITIM-containing collagen receptor LAIR-1 and PECAM-1.  In 2015, Dr Mazharian was awarded a British Heart foundation Intermediate Basic Science Research Fellowship to investigate the regulation of the MAPKs Erk1/2 in platelets by the dual-specificity phosphatases (DUSP) 1 and 6 in megakaryopoiesis and platelet production.

Dr Mazharian has several peer-reviewed publications in leading scientific and biomedical research journals.  She has written book chapters on megakaryocyte migration and signalling events regulating platelet production.  She has been an invited speaker at national and international conferences on platelets and megakaryocytes.


  • Supervising BMedSci students
  • Small Group Teaching BMedSci students
  • Lecture and Small group teaching for MRes Cardiovascular Biology students

Postgraduate supervision

  • Supervising/teaching PhD students


Megakaryocytes are large cells found in the bone marrow that release platelets into the circulation.  The primary physiological function of platelets is to plug holes in damaged blood vessels.  Platelets also play vital roles in inflammation and immunity, vessel development and have been implicated in cancer metastasis.   Too few platelets can result in excessive bleeding following injury, whereas too many platelets can cause unwanted thrombi that block the blood supply to vital organs, including the heart and brain, leading to myocardial infarction and stroke, respectively.  Megakaryocytes must therefore maintain a healthy concentration of platelets in the blood.  A major question in the field is how platelet count and reactivity are regulated in health and disease.  Although much is known about megakaryocyte development and platelet production, relatively little is known about the triggering mechanism of proplatelet formation and platelet release into the circulation.  

Dr Mazharian’s main research interest is the regulation of the MAPKs Erk1/2 in platelets by DUSP1 and DUSP6.  The hypothesis underpinning this project is that Erk1/2 are essential for megakaryocyte development, but must be down-regulated during proplatelet formation.  Dr Mazharian utilizes a multidisciplinary approach to address this question.  Another primary research interest is the co-ordination of platelet production and function by the ITIM-containing receptors LAIR-1 and PECAM-1.

Other activities

  • Member of the Biochemical Society
  • Member of the British Society for Haemostasis and Thrombosis
  • Member of the British Society of Haematology
  • Member of the International Society on Thrombosis and Haemostasis


Cardo L, Thomas SG, Mazharian A, Pikramenou Z, Nash G, Rappoport J, Hannon MJ, Watson SP.  (2015) Accessible synthetic probes to stain actin inside platelets and megakaryocytes employing Lifeact peptide.  ChemBioChem, 16:1680-1688.

Bhavanasi D, Dangelmaier C, Mazharian A, Jin J, Kim S, Zhang X, Chen X, Senis YA, and Kunapuli SP.  (2015) Cross talk between serine/threonine and tyrosine kinases regulates ADP-induced thromboxane generation in platelets.  Thromb. Haemostasis, 114:558-568.

Mazharian A, Senis YA.  (2015) Proplatelets slip sliding’ away.  Blood, 125:747-748

Hobbs CM, Manning H, Bennett C, Vasquez L, Severin S, Brain L, Mazharian A, Li J, Soranzo N, Green AR, Watson SP, Ghevaert C.  (2013) JAK2V617F leads to intrinsic changes in platelet formation and reactivity in a knock-in mouse model of essential thrombocythemia.  Blood, 122:3787-3797.

Zhang L, Urtz N, Gaertner F, Legate KR, Petzold T, Lorenz M, Mazharian A, Watson SP, Massberg S.  (2013) Sphingosine kinase 2 (Sphk2) regulates platelet biogenesis by providing intracellular sphingosine 1-phosphate (S1P).  Blood, 122:791-802. 

Mazharian A, Mori J, Wang YJ, Heising S, Neel BG, Watson SP and Senis YA.  (2013) Megakaryocyte/platelet-specific deletion of the protein-tyrosine phosphatases Shp1 and Shp2 causes abnormal megakaryocyte development, platelet production and function.  Blood, 121: 4205-4220. 

Mazharian A, Wang YJ, Mori J, Bem D, Finney B, Heising S, Gissen P, White JG, Berndt MC, Gardiner EE, Douglas MR, Campbell DR, Watson SP and Senis YA.  (2012)  Severe macrothrombocytopenia and aberrant platelet function in mice lacking the ITIM receptor G6b-BScience Signaling, 5(248):ra78. 

Mazharian A, Ghevaert C, Zhang L, Massberg S and Watson SP.  (2011) Dasatinib enhances megakaryocyte differentiation but inhibits proplatelet formation.  Blood, 117:5198-5206. 

Mazharian A, Thomas SG, Dhanjal T, Buckley C and Watson SP.  (2010) Critical role of Src-Syk-PLCg2 signalling on megakaryocyte migration and thrombopoiesis.  Blood, 116:793-800.  PMID: 20457868.

Mazharian A, Watson SP and Severin S.  (2009) Critical role for ERK1/2 in bone marrow and fetal liver-derived primary megakaryocyte differentiation, motility and proplatelet formation.  Exp. Hematol. 37: 1238–1249. 

Senis YA, Tomlinson MG, Ellison S, Mazharian A, Lim J, Zhao Y, Kornerup KN, Auger JM, Thomas SG, Dhanjal T, Kalia N, Zhu JW, Weiss A and Watson SP.  (2009) The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis.  Blood, 113: 4942-4954. 

Kauskot A, Adam F, Mazharian A, Ajzenberg N, Berrou E, Bonnefoy A, Hoylaerts MF, and Bryckaert M.  (2007) Involvement of the MAP Kinase JNK1 in thrombus formation.  J. Biol. Chem. 282: 31990-31999.  PMID: 17785464.  

Mazharian A, Roger S, Berrou E, Adam F, Kauskot A, Nurden P, Jandrot-Perrus M, and Bryckaert M. (2007) Protease-activated Receptor-4 induces full platelet spreading on a fibrinogen matrix: involvement of ERK2, p38MAPK and Ca2+ mobilization.  J. Biol. Chem. 282: 5478-5487. 

Mazharian A, Roger S, Maurice P, Berrou E, Popoff MR, Hoylaert MF, Fauvel-Lafeve F, Bonnefoy A, and Bryckaert M.  (2005) Differential involvement of ERK2 and p38MAPK in platelet adhesion to collagen.  J. Biol. Chem. 280: 26002-26010. 

Despouy G, Bastie JN, Deshaies S, Balitrand N, Mazharian A,Rochette-Egly C, Chomienne C and Delva L.  (2003) Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of cellular retinoic acid-binding protein II.  J. Biol. Chem. 278: 6355-6362. 


Senis YA, Mazharian A, Mori J.  (2014)  Src family kinases in platelets signaling and activation.  Blood, 124(13):2013-2024. 

Severin S, Ghevaert C, Mazharian A(2009) The mitogen-activated protein kinase signalling     pathway:   role in megakaryocyte differentiation.  J. Thromb. Haemost. 8: 17-26. 

Book Chapter

Mazharian A(2012) Assessment of megakaryocyte migration and chemotaxisPlatelets and Megakaryocytes, Additional Protocols and Perspectives, Volume 3. 788:277-288.