Cellular Hemostasis and Inflammation Research Group

Group leader: Béla Nagy Jr, MD, PhD

Members: György Jázon Balla MD, PhD student; Anita Bartha-Tatár MD; Ildikó Beke Debreceni PhD; Zsolt Fejes MSc, PhD; János Kappelmayer MD, PhD, DSc; Adrienne Kerényi MD, PhD; Bálint Krajcsír PhD student; Marianna Pócsi MSc, PhD student

Technician: Ágnes Nagyné Koroknai

Inflammation is one of the most ancient and common disease processes, which forms the pathophysiological background of many human disorders. Under such conditions, pro-inflammatory mediators/cytokines and metabolic products can directly stimulate platelets, vascular endothelial cells, or respiratory epithelial cells. Thrombosis and bleeding are multicellular events that also implicates the involvement of platelets, leukocytes, and endothelial cells. All these events result in cell dysfunction as well with the release of many protein and nucleic acid components that can act as new laboratory biomarkers.

Our group investigates the effect of different agonists on platelet activation in vitro on the level of various cell surface-associated and soluble markers, such as P-selectin, phosphatidylserine and CD40L, in addition to platelet-leukocyte interactions, coated-platelets,  platelet-derived microparticles, and platelet dependent thrombin generation. Platelet activation is also studied in ex vivo clinical samples from patients with enhanced thrombotic tendency like diabetes mellitus, sepsis, hematological malignancies, and coronary artery disease. These studies are performed in collaboration with the Departments of Internal Medicine and Cardiology, University of Debrecen. In parallel, alteration in RNA expression in platelets and endothelial cells is also intensively examined via the quantification of microRNA and mRNA levels. We maintain regular scientific discussions on these topics with Prof. Satya P. Kunapuli (Temple University, Philadelphia, PA, USA).

In patients with hematologic malignancies, anticancer treatment may cause thrombotic or bleeding events. We examine the effect of these drugs on platelet and endothelial cell activation and its hemostatic consequences. Another aspect of the hemostatic cellular process is the impact of hemorrhage on choroid plexus epithelium following preterm intraventricular hemorrhage (IVH). We evaluate the effects of heme as a major mediator of the damage of choroid plexus epithelium after IVH, which may contribute to neurodevelopmental impairment in preterm infants.

Cystic fibrosis (CF) is an autosomal monogenic disease caused by pathogenic variants in the CFTR gene encoding the anion channel CFTR at the apical surface of epithelial cells that transports chloride and bicarbonate. We analyze the role of human epididymis protein 4 (HE4) as a mediator and a biomarker of CF lung disease. These studies are carried out in collaboration with Prof. Margarida Amaral (University of Lisbon, Lisbon, Portugal) and Prof. Milan Macek Jr. (Charles University, Prague, Check Republic).

The Cellular Hemostasis and Inflammation Group routinely utilizes cell culturing, flow cytometry, RT-qPCR, Western-blotting, thrombin generation assay and ELISA techniques, but we have also access to RNA sequencing and gene silencing via siRNA application.

List of the most relevant publications:

1. Pócsi M, Fejes Z, Bene Z, Nagy A, Balogh I, Amaral MD, Macek M Jr, Nagy B Jr. Human epididymis protein 4 (HE4) plasma concentration inversely correlates with the improvement of cystic fibrosis lung disease in p.Phe508del-CFTR homozygous cases treated with the CFTR modulator lumacaftor/ivacaftor combination. J Cyst Fibros. 2023; 22(6): 1085-1092.
2. Ghansah H, Debreceni IB, Váróczy L, Rejtő L, Lóczi L, Bagoly Z, Kappelmayer J. Patients with multiple myeloma and monoclonal gammopathy of undetermined significance have variably increased thrombin generation and different sensitivity to the anticoagulant effect of activated protein C. Thromb Res. 2023; 223: 44-52.
3. Illési Á, Debreceni IB, Fejes Z, Nagy B Jr, Hodosi K, Kappelmayer J, Csanádi Z, Szük TI. Effect of invasive therapeutic coronary interventions on endothelial cell activation and thrombin generation in patients with chronic total coronary occlusion. Thromb Res. 2022; 217: 64-72.
4. Fejes Z, Pócsi M, Takai J, Erdei J, Tóth A, Balogh E, Rusznyák Á, Fenyvesi F, Nagy A, Kappelmayer J, Jeney V, Nagy B Jr. Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells. Int J Mol Sci. 2021; 22(16): 8648.
5. Ghansah H, Debreceni IB, Fejes Z, Nagy B Jr, Kappelmayer J. The Proteasome Inhibitor Bortezomib Induces Apoptosis and Activation in Gel-Filtered Human Platelets. Int J Mol Sci. 2021; 22(16): 8955.
6. Szilágyi B, Fejes Z, Póliska S, Pócsi M, Czimmerer Z, Patsalos A, Fenyvesi F, Rusznyák Á, Nagy G, Kerekes G, Berhés M, Szűcs I, Kunapuli SP, Kappelmayer J, Nagy B Jr. Reduced miR-26b Expression in Megakaryocytes and Platelets Contributes to Elevated Level of Platelet Activation Status in Sepsis. Int J Mol Sci. 2020; 21(3): 866.
7. Fejes Z, Czimmerer Z, Szük T, Póliska S, Horváth A, Balogh E, Jeney V, Váradi J, Fenyvesi F, Balla G, Édes I, Balla J, Kappelmayer J, Nagy B Jr. Endothelial cell activation is attenuated by everolimus via transcriptional and post-transcriptional regulatory mechanisms after drug-eluting coronary stenting. PLoS One. 2018; 13(6): e0197890.
8. Fejes Z, Póliska S, Czimmerer Z, Káplár M, Penyige A, Gál Szabó G, Beke Debreceni I, Kunapuli SP, Kappelmayer J, Nagy B Jr. Hyperglycaemia suppresses microRNA expression in platelets to increase P2RY12 and SELP levels in type 2 diabetes mellitus. Thromb Haemost. 2017; 117(3): 529-542.
9. Kappelmayer J, Beke Debreceni I, Vida A, Antal-Szalmás P, Clemetson KJ, Nagy B Jr. Distinct effects of Re- and S-forms of LPS on modulating platelet activation. J Thromb Haemost. 2013; 11(4): 775-8.