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Biomembrane Research Group                                                                        photo of Balázs Sarkadi

Group Leader:

Balázs Sarkadi, MD, Ph.D., member of the Hung. Acad. Sci.

E-mail: uh.atm.kttnull@szalab.idakras

Phone: +36 1 382 684


The Biomembrane Group has been recently formed within the Institute of Enzymology, RCNS-HAS, based on the transfer of research laboratories from the National Blood Service and the Institute of Molecular Pharmacology. The group consists of three research laboratories, the Laboratory of Molecular Genetics (head Dr. Tamás Orbán, Ph.D.), the Laboratory of Protein Conformation Diseases (head Ervin Welker, Ph.D.), and the Laboratory of ABC Transporter Biochemistry (head Dr. Ágnes Telbisz, Ph.D.). The Group also hosts the in vitro Virus Laboratory of the Institute of Enzymology (head Áron Szepesi, Ph.D. student). In spite of its relatively recent formation, the group has a long-standing tradition in studying membrane-based phenomena in the human body, thus dealing with normal and pathological functions of membrane transporters and receptors, as well as with the molecular biology background of the expression and regulation of membrane proteins.

The Group closely collaborates with the Molecular Pharmacology Group (group leader Laszlo Homolya), especially in the area of human stem cell biology, flow cytometry studies and membrane protein trafficking. Another long-standing close collaboration exists with the Groups lead by András Váradi (Aktive Transporter Group), and by Gergely Szakács (Membrane Protein Research Group). In addition to these close collaborations within the Institute of Enzymology, we attempt to take advantage of the unique possibilities of the RCNS-HAS, bringing togeteher research groups in chemistry, biology and experimental psychology.

Group photo:

members of the Biomembrane Research Group

Research group members:

Balázs Sarkadi, MD, Ph.D – group leader CV, list of publications

Tamás I. Orbán, Ph.D. – head of the Laboratory of Molecular Genetics CV, list of publications

Ervin Welker, Ph.D. – head of Laboratory of Protein Conformation Diseases CV, list of publications

Ágnes Telbisz, Ph.D. – head of Laboratory of ABC Transporter Biochemistry CV, list of publications

Áron Szepesi, Ph.D. student – head of In Vitro Virus Laboratory CV, list of publications

Biomembrane Group – Laboratory of ABC Transporter Biochemistry

Head of the Laboratory: Dr. Ágnes Telbisz, Ph.D.

ATP Binding Cassette (ABC) transporters have numerous functions in the human body. The efficiency of anti-cancer chemotherapy is strongly hampered by the multidrug (MDR) ABC transporters, which are also key participants in cellular defense and tissue barriers. The role of ABC transporters in drug Absorbtion, Distribution, Metabolism, Excretion and Toxicity (ADME-Tox) is widely appreciated, and current drug development requires the detailed examination of potential new agents with drug transporters.

The laboratory is currently focusing on the expression, characterization, isolation and reconstitution of some key ABC transporters, including ABCG2 (BCRP, MXR), ABCB1 (Pgp, MDR1), ABCB11 (biles salt export pump, BSEP), and ABCB6. By using in vitro expression systems, members of the laboratory study the structure-function relationships of these transporter proteins, establish functional test systems and develop high capacity pharmacological and toxicological assays. A special attention is placed on studying the potential role of mesenchymal stem cells in drug responses and immunosuppression.

Group photo:

members of the Laboratory of ABC Transporter Biochemistry

 
 
 Laboratory members:
 
Ágnes Telbisz, Ph.D., – head of the Laboratory
Katalin Német, Ph.D. scientific adviser
Zsuzsanna Nerada MSc, Ph.D. student
Zsolt Matula Ph.D. student
Zsófia Kocsis – MSc, technician
Anna Szigeti MSc, technician

Former members:

Csilla Laczka, Ph.D.
Csilla Hegedüs, Ph.D.
Tamás Hegedűs, Ph.D.
 
Selected publications:

Hegedüs C, Telbisz Á, Hegedűs T, Sarkadi B, Özvegy-Laczka C. Lipid regulation of the ABCB1 and ABCG2 multidrug transporters. Adv Cancer Res. 2015;125:97-137. doi: 10.1016/bs.acr.2014.10.004. Epub 2015 Jan 8. PubMed PMID: 25640268.

Szepesi Á, Matula Z, Szigeti A, Várady G, Szabó G, Uher F, Sarkadi B, Német K. ABCG2 is a selectable marker for enhanced multilineage differentiation potential in periodontal ligament stem cells. Stem Cells Dev. 2015 Jan 15;24(2):244-52. doi: 10.1089/scd.2014.0177. PubMed PMID: 25101689; PubMed Central PMCID: PMC4291215.

Telbisz Á, Hegedüs C, Váradi A, Sarkadi B, Özvegy-Laczka C. Regulation of the function of the human ABCG2 multidrug transporter by cholesterol and bile acids: effects of mutations in potential substrate and steroid binding sites. Drug Metab Dispos. 2014 Apr;42(4):575-85. doi: 10.1124/dmd.113.055731. Epub 2014 Jan 2. PubMed PMID: 24384916; PubMed Central PMCID: PMC3965895.

Sarankó H, Tordai H, Telbisz Á, Özvegy-Laczka C, Erdős G, Sarkadi B, Hegedűs T. Effects of the gout-causing Q141K polymorphism and a CFTR ?F508 mimicking mutation on the processing and stability of the ABCG2 protein. Biochem Biophys Res Commun. 2013 Jul 19;437(1):140-5. doi: 10.1016/j.bbrc.2013.06.054. Epub 2013 Jun 22. PubMed PMID: 23800412.

Telbisz Á, Özvegy-Laczka C, Hegedűs T, Váradi A, Sarkadi B. Effects of the lipid environment, cholesterol and bile acids on the function of the purified and reconstituted human ABCG2 protein. Biochem J. 2013 Mar 1;450(2):387-95. doi: 10.1042/BJ20121485. PubMed PMID: 23205634.

Tátrai P, Sági B, Szigeti A, Szepesi A, Szabó I, Bősze S, Kristóf Z, Markó K, Szakács G, Urbán I, Mező G, Uher F, Német K. A novel cyclic RGD-containing peptide polymer improves serum-free adhesion of adipose tissue-derived mesenchymal stem cells to bone implant surfaces. J Mater Sci Mater Med. 2013 Feb;24(2):479-88. doi: 10.1007/s10856-012-4809-x. Epub 2012 Nov 8. PubMed PMID: 23135412.

Telbisz Á, Hegedüs C, Özvegy-Laczka C, Goda K, Várady G, Takáts Z, Szabó E, Sorrentino BP, Váradi A, Sarkadi B. Antibody binding shift assay for rapid screening of drug interactions with the human ABCG2 multidrug transporter. Eur J Pharm Sci. 2012 Jan 23;45(1-2):101-9. doi: 10.1016/j.ejps.2011.10.021. Epub 2011 Nov 17. PubMed PMID: 22115866.

Hegedus C, Szakács G, Homolya L, Orbán TI, Telbisz A, Jani M, Sarkadi B. Ins and outs of the ABCG2 multidrug transporter: an update on in vitro functional assays. Adv Drug Deliv Rev. 2009 Jan 31;61(1):47-56. doi:10.1016/j.addr.2008.09.007. Epub 2008 Dec 24. Review. PubMed PMID: 19135105.

Telbisz A, Müller M, Ozvegy-Laczka C, Homolya L, Szente L, Váradi A, Sarkadi B. Membrane cholesterol selectively modulates the activity of the human ABCG2 multidrug transporter. Biochim Biophys Acta. 2007 Nov;1768(11):2698-713. Epub 2007 Jul 10. PubMed PMID: 17662239.

Laboratory of Molecular Genetics

Head of the Laboratory: Dr. Tamás Orbán, Ph.D.

One main research focus of the group is the investigation of DNA transposition in mammalian cells. Apart from understanding the endogenous regulatory mechanisms, we are examining the molecular defense mechanisms against transposition, and the process how DNA transposons can become domesticated during evolution, especially focusing on the human genome. An additional important aspect of our research is the development of transposon-based gene delivery methods: we are investigating the efficiency of the Sleeping Beauty, the piggyBac and the Frog Prince transposon systems in mammalian models, including applications in embryonic stem cells.

The other important research aspect of our group is the investigation of RNA interference pathways, in particular, the alternative processing routes of microRNA maturation. Our primary interest is to decipher the molecular details of the mammalian mirtron pathway. In addition, we are aiming to develop artificial mirtron-derived microRNAs that could be used for future therapeutic applications.

Group photo:

Laboratory of Molecular Genetics

Laboratory members:

Tamás I. Orbán, Ph.D. – principal investigator
Anita Schamberger, Ph.D. – postdoctoral fellow
Orsolya Kolacsek – predoctoral fellow
Sára Sándor – predoctoral fellow
Enikő Pergel – Ph.D. student
Ábel Fóthi – M.Sc. student
Gerda Wachtl – M.Sc. student
Kornélia Némethyné Hupcsik – technician

Former members:

Theodóra Jordanidisz
Zsuzsanna Nagy
Melisa Chikhi
Zsuzsanna Fedor-Sebestyén
Virág Krízsik

Selected publications:

1. Szebényi K, Füredi A, Kolacsek O, Csohány R, Prókai Á, Kis-Petik K, Szabó A, Bősze Z, Bender B, Tóvári J, Enyedi Á, Orbán TI, Apáti Á, Sarkadi B: Visualization of calcium dynamics in rat kidney proximal tubules. Journal of the American Society of Nephrology. 2015, Mar 18. pii: ASN.2014070705. [Epub ahead of print].

2. Schamberger A, Orbán TI: 3’ isomiR species and DNA contamination influence reliable quantification of microRNAs by stem-loop quantitative PCR. PLoS ONE. 2014, 9(8): e106315.

3. Kolacsek O, Erdei Z, Apáti A, Sándor S, Izsvák Z, Ivics Z, Sarkadi B, Orbán TI: Excision efficiency is not strongly coupled to transgenic rate: cell type dependent transposition efficiency of Sleeping Beauty and piggyBac DNA transposons. Human Gene Therapy Methods. 2014, 25(4):241-52.

4. Anita Schamberger and Tamás I. Orbán: Experimental validation of predicted mammalian miRNAs of mirtron origin. In: RNA Mapping, Methods and Protocols, Methods in Molecular Biology, Lucrecia Alvarez and Mahtab Nourbakhsh (Eds.). Springer Verlag, ISBN: 978-1-4939-1061-8, 2014; 1182:245-63.

5. Orsolya Kolacsek, Zsuzsanna Izsvák, Zoltán Ivics, Balázs Sarkadi, Tamás I. Orbán: Quantitative analysis of DNA transposon-mediated gene delivery: the Sleeping Beauty system as an example. In: Genomics III – Methods, Techniques and Applications, iConcept Press Ltd Book, ISBN: 978-1-922227-096, 2014, 97-123.

6. Schamberger A, Sarkadi B, Orban TI: Human mirtrons can express functional microRNAs simultaneously from both arms in a flanking exon-independent manner. RNA Biology. 2012, 9(9):1177-85. (cover page story)

7. Kolacsek O, Krízsik V, Schamberger A, Erdei Z, Apáti Á, Várady G, Mátés L, Izsvák Z, Ivics Z, Sarkadi B, Orbán TI: Reliable transgene-independent method for determining Sleeping Beauty transposon copy numbers. Mobile DNA. 2011, 2(1):5.

8. Tamás I. Orbán, Ágota Apáti, Zsuzsanna Izsvák, Zoltán Ivics and Balázs Sarkadi: Use of Transposon-Transposase Systems for Stable Genetic Modification of Embryonic Stem Cells. In: Methodological Advances in the Culture, Manipulation and Utilization of Embryonic Stem Cells for Basic and Practical Applications, Craig Atwood (Ed.). InTech, ISBN: 978-953-307-197-8; 2011: 259-274.

9. Sarkadi B, Orbán TI, Szakács G, Várady G, Schamberger A, Erdei Z, Szebényi K, Homolya L, Apáti A: Evaluation of ABCG2 expression in human embryonic stem cells: crossing the same river twice? Stem Cells. 2010, 28(1):174-6.

10. Orbán TI, Apáti A, Németh A, Varga N, Krizsik V, Schamberger A, Szebényi K, Erdei Z, Várady G, Karászi E, Homolya L, Német K, Gócza E, Miskey C, Mátés L, Ivics Z, Izsvák Z, Sarkadi B: Applying a “double-feature” promoter to identify cardiomyocytes differentiated from human embryonic stem cells following transposon-based gene delivery. Stem Cells. 2009, 27(5):1077-87.

Biomembrane Group – Laboratory of Protein Conformation Diseases

Head of the Laboratory: Dr. Ervin Welker, Ph.D.

Errors in protein folding and conformations are important factors in numerous human diseases, including Alzheimer’s disease, Parkinson disease, Huntington disease and the prion diseases. In these conditions the deposition of amyloid fibers, mostly containing improperly folded proteins with beta sheet conformation, destroy the cellular functions.

The main interest of the group is the elucidation of the molecular basis of protein misfolding, currently focusing on prion and prion-like proteins, including the Shadoo protein. They study the expression, cellular localization and trafficking, as well as the functional properties of these proteins in cellular and in vivo model systems.

In addition, the group is involved in developing up-to-date molecular biology technologies, currently focusing on the application of an advanced CRISPR-Cas9 technology in mammalian genome editing.

Group photo:

Laboratory of Protein Conformation Diseases members

Laboratory members:

Ervin Welker, Ph.D. – principal investigator - CV
Adrienn Borsy, Ph.D. – postdoctoral fellow
Krisztina Huszár – Ph. D. student
Petra Bencsura Gulácsiné – Ph. D. student
Eszter Tóth – Ph. D. student
Péter István Kulcsár – Ph. D. student
András Tálas – Ph. D. student
Ádám Sturm – Ph. D. student
Antal Nyeste – Ph. D. student
Sara Laura Krausz – M.Sc. student
Judit Szücs – technician
Ildikó Pulinka Szücsné – technician
Judit Baunoch – technician

Biomembrane Group – In vitro Virus Laboratory

Head of the Laboratory: Áron Szepesi, Ph.D. student

In the RCNS-HAS there is a continuous need of applying virus-based vectors for the genetic modification of mammalian cells. Therefore, within the Institute of Enzymology, in 2015 a specialized virus laboratory has been established for in vitro cell-based work. The laboratory has a detailed set of rules assuring the safety of the procedures and the effcient application of viral vectors. The work of the laboratory is supervised by the Virus Committee of the RCNS-HAS, lead by Istvan Ulbert Ph.D., DSc. Áron Szepesi, the head of the laboratory, has more than 5 years of experience working with various viral systems.

Virus-based research in the laboratory can be performed based on a detailed research plan and methodology description, approved by the Virus Committee, and the work is supervised by the head of the Laboratory. Currently there are approved projects applying lentiviral vectors and Sendai viruses.

Publications of Áron Szepesi:

Szepesi Á, Matula Z, Szigeti A, Várady G, Szabó G, Uher F, Sarkadi B, Német K. ABCG2 is a selectable marker for enhanced multilineage differentiation potential in periodontal ligament stem cells. Stem Cells Dev. 2015 Jan 15;24(2):244-52. doi: 10.1089/scd.2014.0177. PubMed PMID: 25101689; PubMed Central PMCID: PMC4291215.

Tátrai P, Sági B, Szigeti A, Szepesi A, Szabó I, Bősze S, Kristóf Z, Markó K, Szakács G, Urbán I, Mező G, Uher F, Német K. A novel cyclic RGD-containing peptide polymer improves serum-free adhesion of adipose tissue-derived mesenchymal stem cells to bone implant surfaces. J Mater Sci Mater Med. 2013 Feb;24(2):479-88. doi: 10.1007/s10856-012-4809-x. Epub 2012 Nov 8. PubMed PMID: 23135412.

Tátrai P, Szepesi Á, Matula Z, Szigeti A, Buchan G, Mádi A, Uher F, Német K. Combined introduction of Bmi-1 and hTERT immortalizes human adipose tissue-derived stromal cells with low risk of transformation. Biochem Biophys Res Commun. 2012 May 25;422(1):28-35. doi: 10.1016/j.bbrc.2012.04.088. Epub 2012 Apr 25. PubMed PMID: 22554522.