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MLDS grant Sabine Daemen

MLDS grant Sabine Daemen

15 November 2024

Dr Sabine Daemen (Dept of Internal Medicine) received a Career Development Grant (160k) from the Dutch Digestive Foundation (MLDS).

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Our new Division Leaders

Our new Division Leaders

3 October 2024

As of 1 October 2024, Casper Schalkwijk and Joost Lumens have been appointed as Division Leaders Vessels and Heart. Judith Sluimer will success Hugo ten Cate as Division Leader Blood in March 2025.

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Carim Maastricht
Carim Maastricht

Elisabetta Castoldi

Associate professor

Dr Elisabetta Castoldi studied Biology (with a major in Molecular Genetics) at Ferrara University (Italy) and graduated cum laudein 1996. After defending her PhD thesis entitled 'Molecular bases of APC resistance and factor V deficiency in thrombophilia' under the supervision of Prof. Francesco Bernardi (2001), she moved to Maastricht University (The Netherlands) for post-doctoral training in coagulation biochemistry in Prof. Jan Rosing’s laboratory. In 2006, she was awarded a Vidi grant from the Netherlands Organisation for Scientific Research (NWO), which allowed her to establish her own research line.

Her research activity focusses on the elucidation of (inherited) coagulation defects that predispose to bleeding or venous thrombosis, with particular reference to factor V, the protein C pathway and the tissue factor pathway inhibitor system. Her work spans the whole flow of genetic information from DNA (mutation screening and interpretation), to RNA (mRNA analysis, with special emphasis on pre-mRNA splicing and its regulation) and protein (functional assays in model systems and in plasma). Most recently, she has been exploringthe unique functional properties of alternatively spliced variants of fibrinogen (fibrinogen γ’) and FV (FV-short).

 

Elisabetta-castoldi

Department of Biochemistry
Universiteitsingel 50, 6229 ER Maastricht
PO Box 616, 6200 MD Maastricht
Room number: H4.356
T: +31(0)43 388 41 60

  • 2024
    • Monard, A., Castoldi, E., De Simone, I., Wichapong, K., van Duijl, T., van den Biggelaar, M., Spada, S., van Doorn, W., Hellenbrand, D., van der Meijden, P., Swieringa, F., Stork, A., ten Cate, H., Beckers, E., Heubel-Moenen, F., & Henskens, Y. (2024). Case Report: Laboratory detection of a thrombotic tendency in a family with hypodysfibrinogenemia and a novel FGG mutation. Frontiers in Cardiovascular Medicine, 11, Article 1488602. https://doi.org/10.3389/fcvm.2024.1488602
    • Diaz, R. V., Munsch, G., Iglesias, M. J., Robles, A. P., Ibrahim-Kosta, M., Nourse, J., Khan, E., Castoldi, E., Saut, N., Boland, A., Germain, M., Deleuze, J.-F., Odeberg, J., Morange, P.-E., Danckwardt, S., Tregouët, D.-A., & Goumidi, L. (2024). Plasma levels of Complement components C5 and C9 are associated with thrombin generation. Journal of Thrombosis and Haemostasis, 22(9), 2531-2542. https://doi.org/10.1016/j.jtha.2024.04.026
    • Todaro, A. M., Radu, C. M., Ciccone, M., Toffanin, S., Serino, M. L., Campello, E., Bulato, C., Lunghi, B., Gemmati, D., Cuneo, A., Hackeng, T. M., Simioni, P., Bernardi, F., & Castoldi, E. (2024). In vitro and ex vivo rescue of a nonsense mutation responsible for severe coagulation factor V deficiency. Journal of Thrombosis and Haemostasis, 22(2), 410-422. https://doi.org/10.1016/j.jtha.2023.10.007
    • Mohapatra, A. K., Todaro, A. M., & Castoldi, E. (2024). Factor V variants in bleeding and thrombosis. Research and practice in thrombosis and haemostasis, 8(1), Article 102330. Advance online publication. https://doi.org/10.1016/j.rpth.2024.102330
  • 2023
    • Danckwardt, S., Tregouet, D.-A., & Castoldi, E. (2023). Post-transcriptional control of haemostatic genes: mechanisms and emerging therapeutic concepts in thrombo-inflammatory disorders. Cardiovascular Research, 119(8), 1624-1640. https://doi.org/10.1093/cvr/cvad046
    • Castoldi, E. (2023). Making sense of FV short. Blood, 141(26), 3134-3135. https://doi.org/10.1182/blood.2023020274
    • Moore, G. W., Castoldi, E., Teruya, J., Morishita, E., & Adcock, D. M. (2023). Factor V Leiden-independent activated protein C resistance: Communication from the plasma coagulation inhibitors subcommittee of the International Society on Thrombosis and Haemostasis Scientific and Standardisation Committee. Journal of Thrombosis and Haemostasis, 21(1), 164-174. https://doi.org/10.1016/j.jtha.2022.10.014
  • 2021
    • Todaro, A. M., Hackeng, T. M., & Castoldi, E. (2021). Antisense-Mediated Down-Regulation of Factor V-Short Splicing in a Liver Cell Line Model. Applied Sciences, 11(20), Article 9621. https://doi.org/10.3390/app11209621
    • Castoldi, E. (2021). F5-Atlanta: Factor V-short strikes again. Journal of Thrombosis and Haemostasis, 19(7), 1638-1640. https://doi.org/10.1111/jth.15351
    • Denisov, S. S., Ippel, J. H., Castoldi, E., Mans, B. J., Hackeng, T. M., & Dijkgraaf, I. (2021). Molecular basis of anticoagulant and anticomplement activity of the tick salivary protein Salp14 and its homologs. Journal of Biological Chemistry, 297(1), Article 100865. https://doi.org/10.1016/j.jbc.2021.100865
    • Iding, A. F. J., Witten, A., Isaacs, A., Castoldi, E., ten Cate, H., Stoll, M., & ten Cate-Hoek, A. J. (2021). Leukocyte gene expression in post-thrombotic syndrome. Thrombosis Research, 202, 40-42. https://doi.org/10.1016/j.thromres.2021.03.007
    • Castoldi, E., Hézard, N., Mourey, G., Wichapong, K., Poggi, M., Ibrahim-Kosta, M., Thomassen, M. C. L. G. D., Fournel, A., Hayward, C. P. M., Alessi, M.-C., Hackeng, T. M., Rosing, J., & Morange, P.-E. (2021). Severe thrombophilia in a factor V-deficient patient homozygous for the Ala2086Asp mutation (FV Besançon). Journal of Thrombosis and Haemostasis, 19(5), 1186-1199. https://doi.org/10.1111/jth.15274
    • Simioni, P., Cagnin, S., Sartorello, F., Sales, G., Pagani, L., Bulato, C., Gavasso, S., Nuzzo, F., Chemello, F., Radu, C. M., Tormene, D., Spiezia, L., Hackeng, T. M., Campello, E., & Castoldi, E. (2021). Partial F8 gene duplication (factor VIII Padua) associated with high factor VIII levels and familial thrombophilia. Blood, 137(17), 2383-2393. https://doi.org/10.1182/blood.2020008168
    • Omarova, F., Rosing, J., Bertina, R. M., & Castoldi, E. (2021). Negatively charged phospholipids stimulate factor XI activation by thrombin. Thrombosis Update, 2, Article 100022. https://doi.org/10.1016/j.tru.2020.100022
    • Brinkman, H. J. M., Ahnstrom, J., Castoldi, E., Dahlback, B., & Marlar, R. A. (2021). Pleiotropic anticoagulant functions of protein S, consequences for the clinical laboratory. Communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis, 19(1), 281-286. https://doi.org/10.1111/jth.15108
  • 2020
    • Brouns, S. L. N., van Geffen, J. P., Campello, E., Swieringa, F., Spiezia, L., van Oerle, R., Provenzale, I., Verdoold, R., Farndale, R. W., Clemetson, K. J., Spronk, H. M. H., van der Meijden, P. E. J., Cavill, R., Kuijpers, M. J. E., Castoldi, E., Simioni, P., & Heemskerk, J. W. M. (2020). Platelet-primed interactions of coagulation and anticoagulation pathways in flow-dependent thrombus formation. Scientific Reports, 10(1), Article 11910. https://doi.org/10.1038/s41598-020-68438-9
    • Ariens, R., Becattini, C., Bender, M., Bergmeier, W., Castoldi, E., Devreese, K., Ellis, M., Gailani, D., Ignjatovic, V., James, P. D., Kerrigan, S., Lambert, M., Lee, L. H., Levi, M., Maugeri, N., Meijers, J., Melero-Martin, J., Michelson, A. D., Mingozzi, F., ... Weisel, J. (2020). Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress. Research and practice in thrombosis and haemostasis, 4(5), 680-713. https://doi.org/10.1002/rth2.12368
    • van Doorn, P., Rosing, J., Campello, E., Middeldorp, S., Simioni, P., Meijers, J. C. M., Hackeng, T. M., & Castoldi, E. (2020). Development of a Plasma-Based Assay to Measure the Susceptibility of Factor V to Inhibition by the C-Terminus of TFPIα. Thrombosis and Haemostasis, 120(1), 55-64. https://doi.org/10.1055/s-0039-1700516
  • 2019
    • van Doorn, P., Rosing, J., Wielders, S. J., Hackeng, T. M., & Castoldi, E. (2019). Corrigendum: The C-terminus of tissue factor pathway inhibitor-a inhibits factor V activation by protecting the Arg(1545) cleavage site (vol 15, pg 140, 2017). Journal of Thrombosis and Haemostasis, 17(7), 1195-1195. https://doi.org/10.1111/jth.14489
    • Ibrahim-Kosta, M., Suchon, P., Couturaud, F., Smadja, D., Olaso, R., Germain, M., Saut, N., Goumidi, L., Derbois, C., Thibord, F., Debette, S., Amouyel, P., Deleuze, J. F., van Doorn, P., Castoldi, E., Patin, E., Alessi, M. C., Tregouet, D. A., & Morange, P. E. (2019). Minor allele of the factor V K858R variant protects from venous thrombosis only in non-carriers of factor V Leiden mutation. Scientific Reports, 9(1), Article 3750. https://doi.org/10.1038/s41598-019-40172-x
  • 2018
    • van Doorn, P., Rosing, J., Duckers, C., Hackeng, T. M., Simioni, P., & Castoldi, E. (2018). Factor V Has Anticoagulant Activity in Plasma in the Presence of TFPI: Difference between FV1 and FV2. Thrombosis and Haemostasis, 118(7), 1194-1202. https://doi.org/10.1055/s-0038-1656549
    • De Maertelaere, E., Castoldi, E., Van Haute, I., Deeren, D., & Devreese, K. M. (2018). The interaction of factor V and tissue factor pathway inhibitor in a myeloma patient with acquired factor V deficiency. Haemophilia, 24(3), E160-E163. https://doi.org/10.1111/hae.13492
  • 2017
    • Nuzzo, F., Beshlawi, I., Wali, Y., & Castoldi, E. (2017). High incidence of intracranial bleeding in factor V-deficient patients with homozygous F5 splicing mutations. British Journal of Haematology, 179(1), 163-166. https://doi.org/10.1111/bjh.14195
    • Alshaikh, N. A., Rosing, J., Thomassen, M. C. L. G. D., Castoldi, E., Simioni, P., & Hackeng, T. M. (2017). New functional assays to selectively quantify the activated protein C- and tissue factor pathway inhibitor-cofactor activities of protein S in plasma. Journal of Thrombosis and Haemostasis, 15(5), 950-960. https://doi.org/10.1111/jth.13657
    • van Doorn, P., Rosing, J., Wielders, S. J., Hackeng, T. M., & Castoldi, E. (2017). The C-terminus of tissue factor pathway inhibitor-alpha inhibits factor V activation by protecting the Arg(1545) cleavage site. Journal of Thrombosis and Haemostasis, 15(1), 140-149. https://doi.org/10.1111/jth.13559
  • 2016
    • Radu, C. M., Spiezia, L., Bulato, C., Gavasso, S., Campello, E., Sartorello, F., Castoldi, E., & Simioni, P. (2016). Endocytosis of exogenous factor V by ex-vivo differentiated megakaryocytes from patients with severe parahaemophilia. British Journal of Haematology, 175(3), 517-524. https://doi.org/10.1111/bjh.14262
    • Dargaud, Y., Jourdy, Y., Le Quellec, S., Hemker, H., Lindhout, T., Castoldi, E., & Negrier, C. (2016). Effect of five therapeutic strategies on the coagulation defect induced by the thrombomodulin c.1611C > A mutation. British Journal of Haematology, 174(6), 993-996. https://doi.org/10.1111/bjh.13833
    • Pezeshkpoor, B., Castoldi, E., Mahler, A., Hanel, D., Mueller, J., Hamedani, N. S., Biswas, A., Oldenburg, J., & Pavlova, A. (2016). Identification and functional characterization of a novel F5 mutation (Ala512Val, FVBonn) associated with activated protein C resistance. Journal of Thrombosis and Haemostasis, 14(7), 1353-1363. https://doi.org/10.1111/jth.13339
    • Cheung, Y. W., Bouman, A. C., Castoldi, E., Wielders, S. J., Spronk, H. M. H., ten Cate, H., Hoek - ten Cate, A., & ten Wolde, M. (2016). Toll-like receptor 9 gene expression in the post-thrombotic syndrome, residual thrombosis and recurrent deep venous thrombosis: A case-control study. Thrombosis Research, 140, 106-109. https://doi.org/10.1016/j.thromres.2016.02.025
    • Mattheij, N. J. A., Braun, A., van Kruchten, R., Castoldi, E., Pircher, J., Baaten, C. C. F. M. J., Wuelling, M., Kuijpers, M. J. E., Koehler, R., Poole, A. W., Schreiber, R., Vortkamp, A., Collins, P. W., Nieswandt, B., Kunzelmann, K., Cosemans, J. M. E. M., & Heemskerk, J. W. M. (2016). Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling, swelling, and protein cleavage. Faseb Journal, 30(2), 727-737. https://doi.org/10.1096/fj.15-280446
    • Mattheij, N., Braun, A., van Kruchten, R., Castoldi, E., PIRCHER, J., Baaten, C., WÜLLING, M., Kuijpers, M., KÖHLER, R., POOLE, A. W., Schreiber, R., VORTKAMP, A., COLLINS, P. W., Nieswandt, B., KUNZELMANN, K., Cosemans, J., & Heemskerk, J. (2016). Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling and swelling. Nederlands tijdschrift voor klinische chemie en laboratoriumgeneeskunde, 41(3), 207-208. https://www.nvkc.nl/sites/default/files/NTKC/Mattheij.pdf
  • 2015
    • Nuzzo, F., Bulato, C., Nielsen, B. I., Lee, K., Wielders, S. J., Simioni, P., Key, N. S., & Castoldi, E. (2015). Characterization of an apparently synonymous F5 mutation causing aberrant splicing and factor V deficiency. Haemophilia, 21(2), 241-248. https://doi.org/10.1111/hae.12554
    • Dargaud, Y., Scoazec, J. Y., Wielders, S. J. H., Trzeciak, C., Hackeng, T. M., Negrier, C., Hemker, H. C., Lindhout, T., & Castoldi, E. (2015). Characterization of an autosomal dominant bleeding disorder caused by a thrombomodulin mutation. Blood, 125(9), 1497-1501. https://doi.org/10.1182/blood-2014-10-604553
    • Nuzzo, F., Paraboschi, E. M., Straniero, L., Pavlova, A., Duga, S., & Castoldi, E. (2015). Identification of a novel large deletion in a patient with severe factor V deficiency using an in-house F5 MLPA assay. Haemophilia, 21(1), 140-147. https://doi.org/10.1111/hae.12536
  • 2014
    • Omarova, F., de Willige, S. U., Simioni, P., Ariens, R. A. S., Bertina, R. M., Rosing, J., & Castoldi, E. (2014). Fibrinogen gamma ' increases the sensitivity to activated protein C in normal and factor V Leiden plasma. Blood, 124(9), 1531-1538. https://doi.org/10.1182/blood-2014-02-554055
    • Castoldi, E. (2014). FV and APC resistance: the plot thickens. Blood, 123(15), 2288-2289. https://doi.org/10.1182/blood-2014-02-557363
    • Segers, O., Simioni, P., Tormene, D., & Castoldi, E. (2014). Influence of single nucleotide polymorphisms on thrombin generation in factor V Leiden heterozygotes. Thrombosis and Haemostasis, 111(3), 438-446. https://doi.org/10.1160/TH13-05-0360
  • 2013
    • Nuzzo, F., Radu, C., Baralle, M., Spiezia, L., Hackeng, T. M., Simioni, P., & Castoldi, E. (2013). Antisense-based RNA therapy of factor V deficiency: in vitro and ex vivo rescue of a F5 deep-intronic splicing mutation. Blood, 122(23), 3825-3831. https://doi.org/10.1182/blood-2013-04-499657
    • Omarova, F., De Willige, S. U., Ariens, R. A. S., Rosing, J., Bertina, R. M., & Castoldi, E. (2013). Inhibition of thrombin-mediated factor V activation contributes to the anticoagulant activity of fibrinogen gamma '. Journal of Thrombosis and Haemostasis, 11(9), 1669-1678. https://doi.org/10.1111/jth.12354
  • 2012
    • Segers, O., Simioni, P., Tormene, D., Bulato, C., Gavasso, S., Rosing, J., & Castoldi, E. (2012). Genetic modulation of the FVLeiden/normal FV ratio and risk of venous thrombosis in factor V Leiden heterozygotes. Journal of Thrombosis and Haemostasis, 10(1), 73-80. https://doi.org/10.1111/j.1538-7836.2011.04546.x
  • 2011
    • Winckers, K., Siegerink, B., Duckers, C., Maurissen, L. F., Tans, G., Castoldi, E., Spronk, H. M. H., Ten Cate, H., Algra, A., Hackeng, T. M., & Rosendaal, F. R. (2011). Increased tissue factor pathway inhibitor activity is associated with myocardial infarction in young women: results from the RATIO study. Journal of Thrombosis and Haemostasis, 9(11), 2243-2250. https://doi.org/10.1111/j.1538-7836.2011.04497.x
    • Castoldi, E., Duckers, C., Radu, C. M., Spiezia, L., Rossetto, V., Tagariello, G., Rosing, J., & Simioni, P. (2011). Homozygous F5 deep-intronic splicing mutation resulting in severe factor V deficiency and undetectable thrombin generation in platelet-rich plasma. Journal of Thrombosis and Haemostasis, 9(5), 959-968. https://doi.org/10.1111/j.1538-7836.2011.04237.x
    • Castoldi, E., & Rosing, J. (2011). Thrombin generation tests. Thrombosis Research, 127(SUPPL. 3), S21-S25. https://doi.org/10.1016/S0049-3848(11)70007-X
  • 2010
    • Castoldi, E., Maurissen, L. F. A., Tormene, D., Spiezia, L., Gavasso, S., Radu, C. M., Hackeng, T. M., Rosing, J., & Simioni, P. (2010). Similar hypercoagulable state and thrombosis risk in type I and type III protein S-deficient individuals from families with mixed type I/III protein S deficiency. Haematologica-the Hematology Journal, 95(9), 1563-1571. https://doi.org/10.3324/haematol.2010.021923
    • Maurissen, L. F. A., Castoldi, E., Simioni, P., Rosing, J., & Hackeng, T. M. (2010). Thrombin generation-based assays to measure the activity of the TFPI-protein S pathway in plasma from normal and protein S-deficient individuals. Journal of Thrombosis and Haemostasis, 8(4), 750-758. https://doi.org/10.1111/j.1538-7836.2010.03743.x
    • Castoldi, E., & Rosing, J. (2010). APC resistance: biological basis and acquired influences. Journal of Thrombosis and Haemostasis, 8(3), 445-453. https://doi.org/10.1111/j.1538-7836.2009.03711.x
    • Castoldi, E., Simioni, P., Tormene, D., Rosing, J., & Hackeng, T. M. (2010). Hereditary and acquired protein S deficiencies are associated with low TFPI levels in plasma. Journal of Thrombosis and Haemostasis, 8(2), 294-300. https://doi.org/10.1111/j.1538-7836.2009.03712.x
    • Duckers, C., Simioni, P., Spiezia, L., Radu, C. M., Dabrilli, P., Gavasso, S., Rosing, J., & Castoldi, E. (2010). Residual platelet factor V ensures thrombin generation in patients with severe congenital factor V deficiency and mild bleeding symptoms. Blood, 115(4), 879-886. https://doi.org/10.1182/blood-2009-08-237719
    • Segers, O., van Oerle, R., ten Cate, H., Rosing, J., & Castoldi, E. (2010). Thrombin generation as an intermediate phenotype for venous thrombosis A proof-of-concept study. Thrombosis and Haemostasis, 103(1), 114-122. https://doi.org/10.1160/TH09-06-0356
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