Group leader: Mária Deli

Email: deli.maria[at]brc.hu

Group website:


 

Group members


Name

Title

Publications

CV

Mária DELI

scientific advisor

publications

CV

Szilvia VESZELKA

senior research associate

publications

CV

Zsófia HOYK

research associate

publications

CV

Fruzsina WALTER

research associate

publications

CV

Alexandra BOCSIK

research associate

publications

CV

András HARAZIN

research associate

publications

CV

Mária MÉSZÁROS

research associate

publications

CV

Ilona GRÓF

junior research associate

publications

CV

Lilla BARNA

research associate

publications

CV

Beáta BARABÁSI

PhD student

publications

CV

Judit VIGH

PhD student

publications

CV

Gergő PORKOLÁB

PhD student

publications

CV

Emese Kincső PÁLI

Szent-Györgyi student

publications

CV

Anna HEGYI

Szent-Györgyi student

publications

CV


 

Research

 

1) Modeling biological barriers with chip devices

The main focus of our research group is the investigation of biological barriers ̶ such as the gut or lung epithelial barriers and the endothelial blood-brain barrier (BBB) ̶ using cell culture models. In our experiments complex co-culture models from multiple cell types are used to better mimick organs and organ systems (Figure 1). Our aim is to establish a new generation of barrier culture models using human stem cells as well as microfluidic and microelectronic chip devices to investigate disease patomechanisms and drug delivery across biological barriers.

Figure 1. Tools to model biological barriers under dynamic (A, B) and static (C) conditions. The microfluidic biochip device enables the introduction of fluid flow (mimicking blood flow) to create physiologically more relevant models.

We utilize static, cell culture insert-based as well as dynamic, biochip-based models developed by our team (Walter et al., 2016; Kincses et al., 2020; Santa-Maria et al., 2021; Figure 1). These devices are cutting edge tools to study biological barriers and enable us to create a solid basis for further innovative research and drug development.

2) Improving drug delivery across biological barriers

Biological barriers, including the epithelium of the intestinal and respiratory systems and the endothelium lining the inner surface of blood vessels, protect organisms from damaging agents and create homeostasis for physiological functions. These barriers, however, also hinder drug penetration and thereby the effective treatment of several diseases. Our team investigates new methods with different approches to enhance drug penetration across barriers. Peptides acting on tight junction proteins can be used to open the paracellular route in epithelial and endothelial cell layers (Bocsik et al., 2019). We also use nanoparticles functionalized with multiple ligands targeting BBB transporters that can deliver their cargo across the BBB and into multiple cell types in the brain (Mészáros et al., 2018; Porkoláb et al., 2020; Figure 2).

Figure 2. Nanoparticles targeting nutrient transporters of brain endothelial cells can enhance drug delivery across the blood-brain barrier and into pericytes, astrocytes and neurons.

3) Dysfunction of biological barriers and their protection

As the main role of biological barriers is to protect certain organs, their dysfunction in different diseases can have serious health consequences. BBB damage is a common feature of central nervous system pathologies that either causes the disease or worsens its progress. Our goal is to identify key factors in the development of diseases that effect barrier functions and to find potential compounds to protect or restore the integrity of barriers. In recent years we have investigated pathomechanisms and protection strategies in several brain-related diseases such as Alzheimer’s disease (Veszelka et al., 2013), epilepsy (Barna et al., 2020), acute pancreatitis or obesity (Ardid-Ruiz et al., 2020).


 

Selected publications

Ardid-Ruiz A, Harazin A, Barna L, et al. The effects of Vitis vinifera L. phenolic compounds on a blood-brain barrier culture model: Expression of leptin receptors and protection against cytokine-induced damage. J Ethnopharmacol. 2020;247:112253.

Barna L, Walter FR, Harazin A, et al. Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage. Fluids Barriers CNS. 2020;17:5.

Bocsik A, Gróf I, Kiss L, Ötvös F, Zsíros O, Daruka L, Fülöp L, Vastag M, Kittel Á, Imre N, Martinek TA, Pál C, Szabó-Révész P, Deli MA. Dual action of the PN159/KLAL/MAP peptide: increase of drug penetration across Caco-2 intestinal barrier model by modulation of tight junctions and plasma membrane permeability. Pharmaceutics. 2019;11:73.

Kincses A, Santa-Maria AR, Walter FR, Dér L, Horányi N, Lipka DV, Valkai S, Deli MA, Dér A. A chip device to determine surface charge properties of confluent cell monolayers by measuring streaming potential. Lab Chip. 2020;20:3792-3805.

Mészáros M, Porkoláb G, Kiss L, et al. Niosomes decorated with dual ligands targeting brain endothelial transporters increase cargo penetration across the blood-brain barrier. Eur J Pharm Sci. 2018;123:228-240.

Porkoláb G, Mészáros M, Tóth A, Szecskó A, Harazin A, Szegletes Z, Ferenc G, Blastyák A, Mátés L, Rákhely G, Deli MA, Veszelka S. Combination of alanine and glutathione as targeting ligands of nanoparticles enhances cargo delivery into the cells of the neurovascular unit. Pharmaceutics. 2020;12:635.

Santa-Maria AR, Walter FR, Figueiredo R, Kincses A, Vigh JP, Heymans M, Culot M, Winter P, Gosselet F, Dér A, Deli MA. Flow induces barrier and glycocalyx-related genes and negative surface charge in a lab-on-a-chip human blood-brain barrier model. J Cereb Blood Flow Metab. 2021 (in press)

Veszelka S, Tóth AE, Walter FR, et al. Docosahexaenoic acid reduces amyloid-β induced toxicity in cells of the neurovascular unit. J Alzheimers Dis. 2013;36:487-501.

Walter FR, Valkai S, Kincses A, Petneházi A, Czeller T, Veszelka S, Ormos P, Deli MA, Dér A. A versatile lab-on-a-chip tool for modeling biological barriers. Sens Actuators B:Chem. 2016;222:1209-1219.