Bachelot-Loza Christilla

CRHC, Inserm

Research theme : Theme 2 – Part 1
Contact

Phone: 01 53 73 96 19

Biography

Christilla BACHELOT-LOZA’s team aims at identifying new mechanisms regulating platelet activation. Within this scope, the cyclic nucleotide pathway is a major player. Indeed, a high platelet level of cAMP (or cGMP) maintains circulating platelets in an inactivated state. This pathway is targeted by anti P2Y12 agents and molecules activating adenylate cyclase.

Main tasks are:

  • To characterize the molecular mechanisms of cyclic nucleotide compartmentation between microdomains, cytosol and dense granules, notably via MRP4 transporter
  • To develop strategies to reverse the effects of ticagrelor, a new potent anti P2Y12 molecule
  • To address these aims, we have several mouse models deleted for proteins involved in these pathways as well as human platelet deficiencies
  • To characterize platelet signalling defect in patients presenting thrombotic or haemorrhagic event

    Major publications 2020 / 2013

    Epinephrine restores platelet functions inhibited by ticagrelor: A mechanistic approach. Anne-Céline Martin, Diane Zlotnik, Guillaume Porta Bonete, Elodie Baron, Benoît Decouture, Tiphaine Belleville-Rolland, Bernard Le Bonniec, Sonia Poirault-Chassac, Marie-Christine Alessi, Pascale Gaussem, Anne Godier, Christilla Bachelot-Loza – 2020 Jan 5 – PMID: 31738933 DOI: 10.1016/j.ejphar.2019.172798

    Effect of rivaroxaban and dabigatran on platelet functions: in vitro study. Georges Jourdi, Christilla Bachelot-Loza, Elisabeth Mazoyer, Sonia Poirault-Chassac, Jerome Duchemin, Michaela Fontenay, Pascale Gaussem – 2019 Nov – PMID: 31678711 DOI: 10.1016/j.thromres.2019.10.007

    Evaluation of commonly used tests to measure the effect of single-dose aspirin on mouse hemostasis. Benoit Decouture, Alexandre Leuci, Blandine Dizier, Tiphaine Belleville-Rolland, Alexandre Mansour, Fanny Martin, Dominique Pidard, Pascale Gaussem, Christilla Bachelot-Loza – PMID: 31442897 DOI: 10.1016/j.plefa.2019.08.002

    Murine platelet production is suppressed by S1P release in the hematopoietic niche, not facilitated by blood S1P sensing. Niazi H, Zoghdani N, Couty L, Leuci A, Nitzsche A, Allende ML, Mariko B, Ishaq R, Aslan Y, Becker PH, Gazit SL, Poirault-Chassac S, Decouture B, Baudrie V, De Candia E, Kono M, Benarab A, Gaussem P, Tharaux PL, Chun J, Provot S, Debili N, Therond P, Proia RL, Bachelot-Loza C, Camerer E. Blood Adv. 2019 Jun 11;3(11):1702-1713. doi: 10.1182/bloodadvances.

    Evolution of platelet functions in cirrhotic patients undergoing liver transplantation: A prospective exploration over a month. Eyraud D, Suner L, Dupont A, Bachelot-Loza C, Smadja DM, Helley D, Bertil S, Gostian O, Szymezak J, Loncar Y, Puybasset L, Lebray P, Vezinet C, Vaillant JC, Granger B, Gaussem P. PLoS One. 2018 Aug 2;13(8):e0200364. doi: 10.1371/journal.pone.0200364.

    Platelet-mapping assay for monitoring antiplatelet therapy during mechanical circulatory support in children: A retrospective observational study. Giorni C, Costopoulos M, Bachelot-Loza C, Belleville-Rolland T, Pouard P, Raisky O, Pascreau T, Borgel D, Lasne D. Res Pract Thromb Haemost. 2017 Jun 20;1(1):120-127. doi: 10.1002/rth2.12010. eCollection 2017 Jul.

    Evidence that MRP4 is Only Partly Involved in S1P Secretion during Platelet Activation. Decouture B, Becker PH, Therond P, Gaussem P, Bachelot-Loza C. Thromb Haemost. 2018 Jun;118(6):1116-1118. doi: 10.1055/s-0038-1641754.

    Human endoglin as a potential new partner involved in platelet-endothelium interactions. Rossi E, Pericacho M, Bachelot-Loza C, Pidard D, Gaussem P, Poirault-Chassac S, Blanco FJ, Langa C, González-Manchón C, Novoa JML, Smadja DM, Bernabeu C. Cell Mol Life Sci. 2018 Apr;75(7):1269-1284. doi: 10.1007/s00018-017-2694-7.

    [Antiplatelet agents and transfusion]. Gaussem P, Martin AC, Belleville-Rolland T, Helley D, Bachelot-Loza C, Godier A. Transfus Clin Biol. 2017 Sep;24(3):160-165. doi: 10.1016/j.tracli.2017.05.014. Epub 2017 Jun 20. Review. French.

    Synergistic effect of peptide inhibitors derived from the extracellular and intracellular domain of αIIb subunit of integrin αIIbβ3 on platelet activation and aggregation. Gkourogianni AV, Kiouptsi K, Koloka V, Moussis V, Tsikaris V, Bachelot-Loza C, Tsoukatos DC. Platelets. 2018 Jan;29(1):34-40. doi: 10.1080/09537104.2017.1293804.

    Ticagrelor reversal: in vitro assessment of four haemostatic agents. Calmette L, Martin AC, Le Bonniec B, Zlotnik D, Gouin-Thibault I, Bachelot-Loza C, Gaussem P, Godier A. J Clin Pathol. 2017 Sep;70(9):733-739. doi: 10.1136/jclinpath-2016-204117.

    Platelet and Erythrocyte Sources of S1P Are Redundant for Vascular Development and Homeostasis, but Both Rendered Essential After Plasma S1P Depletion in Anaphylactic Shock. Gazit SL, Mariko B, Thérond P, Decouture B, Xiong Y, Couty L, Bonnin P, Baudrie V, Le Gall SM, Dizier B, Zoghdani N, Ransinan J, Hamilton JR, Gaussem P, Tharaux PL, Chun J, Coughlin SR, Bachelot-Loza C, Hla T, Ho-Tin-Noé B, Camerer E. Circ Res. 2016 Sep 30;119(8):e110-26. doi: 10.1161/CIRCRESAHA.116.308929.

    MRP4 (ABCC4) as a potential pharmacologic target for cardiovascular disease. Belleville-Rolland T, Sassi Y, Decouture B, Dreano E, Hulot JS, Gaussem P, Bachelot-Loza C. Pharmacol Res. 2016 May;107:381-389. doi: 10.1016/j.phrs.2016.04.002. Epub 2016 Apr 5. Review.

    The effectiveness of platelet supplementation for the reversal of ticagrelor-induced inhibition of platelet aggregation: An in-vitro study. Martin AC, Berndt C, Calmette L, Philip I, Decouture B, Gaussem P, Gouin-Thibault I, Samama CM, Bachelot-Loza C, Godier A. Eur J Anaesthesiol. 2015.

    Inhibition of αIIbβ3 Ligand Binding by an αIIb Peptide that Clasps the Hybrid Domain to the βI Domain of β3. Lee WH, Schaffner-Reckinger E, Tsoukatos DC, Aylward K, Moussis V, Tsikaris V, Trypou P, Egot M, Baruch D, Kieffer N, Bachelot-Loza C. PLoS One. 2015;10:e0134952.

    Impaired platelet activation and cAMP homeostasis in MRP4-deficient mice. Decouture B, Dreano E, Belleville-Rolland T, Kuci O, Dizier B, Bazaa A, Coqueran B, Lompre AM, Denis CV, Hulot JS, Bachelot-Loza C*, Gaussem P*. Blood. 2015: blood-2015-. [Epub ahead of print] * co-last authors, CBL being corresponding author

    Another “string to the bow” of PJ34, a potent poly(ADP-Ribose)polymerase inhibitor: an antiplatelet effect through P2Y12 antagonism? Lechaftois M, Dreano E, Palmier B, Margaill I, Marchand-Leroux C, Bachelot-Loza C, Lerouet D. PLoS One. 2014;9:e110776.

    Impact of aspirin and clopidogrel interruption on platelet function in patients undergoing major vascular surgery. Le Manach Y, Kahn D, Bachelot-Loza C, Le Sache F, Smadja DM, Remones V, Loriot MA, Coriat P, Gaussem P. PLoS One. 2014;9:e104491.

    Palmitoylated peptide, being derived from the carboxyl-terminal sequence of the integrin αIIb cytoplasmic domain, inhibits talin binding to αIIbβ₃. Gkourogianni A, Egot M, Koloka V, Moussis V, Tsikaris V, Panou-Pomonis E, Sakarellos-Daitsiotis M, Bachelot-Loza C, Tsoukatos DC. Platelets. 2014;25:619-27.

    Biphasic myosin II light chain activation during clot retraction. Egot M, Kauskot A, Lasne D, Gaussem P, Bachelot-Loza C. Thromb Haemost. 2013;110:1215-22.

    Platelet dysfunction associated with the novel Trp29Cys thromboxane A₂ receptor variant. Mumford AD, Nisar S, Darnige L, Jones ML, Bachelot-Loza C, Gandrille S, Zinzindohoue F, Fischer AM, Mundell SJ, Gaussem P; UK GAPP Study Group. J Thromb Haemost. 2013;11:547-54