General Overview

The Molecular Cell Biology Research Group investigates the biology of membrane transporter proteins, pluripotent stem cells, and stem cell differentiation; as well as explores their role in the pathophysiology of diseases by means of various cellular models. Using a variety of molecular biological, biochemical and cell biology approaches, we aim at establishing novel diagnostic methods, revealing novel therapeutic targets, as well as developing cellular assay systems and disease models. Our research group consists of three collaborating subunits: the Laboratory of Cell Polarity and Trafficking headed by László Homolya, the Human Pluripotent Stem Cell Lab headed by Ágota Apáti, and the Flow Cytometry Lab headed by György Várady.

Laboratory of Cell Polarity and Trafficking

Head of the laboratory: László Homolya, D.Sc.

The physiological barriers of our body are formed by polarized epithelial and endothelial cells. Membrane transporter proteins, localized in the membrane of these cells in a regulated fashion, control the translocation of various substances, such as nutrients, toxins, and drug molecules. Our research focuses on the better understanding of the establishment and maintenance of cell polarity; the targeting and trafficking of transporter proteins to the proper membrane compartment; and how the genetic alterations – especially disease-causing mutations – in the transporters affect their cellular routing and consequently their function.

Selected publications:

  1. Lilienberg J, Hegyi Z, Szabó E, Hathy E, Málnási-Csizmadia A, Réthelyi JM, Apáti Á, and Homolya L. Pharmacological Modulation of Neurite Outgrowth in Human Neural Progenitor Cells by Inhibiting Non-muscle Myosin II. Front Cell Dev Biol. 9:719636. doi: 10.3389/fcell.2021.719636. eCollection (2021)
  2. Bartos Z. and Homolya L.: Identification of specific trafficking defects of naturally occurring variants of the human ABCG2 transporter. Front Cell Dev Biol 9:615729. (2021)
  3. Török G, Erdei Z, Lilienberg J, Apáti Á, and Homolya L. The importance of transporters and cell polarization for the evaluation of human stem cell-derived hepatic cells. PLoS One 15(1) e0227751 , 22 p. (2020)
  4. Homolya L, Fu D, Sengupta P, Jarnik M, Gillet JP, Vitale-Cross L, Gutkind JS, Lippincott-Schwartz J, and Arias IM: LKB1/AMPK and PKA Control ABCB11 Trafficking and Polarization in Hepatocytes.PLOS ONE 9:(3) p. e91921. (2014)
  5. Homolya L, Orbán TI, Csanády L, and Sarkadi B. Mitoxantrone is expelled by the ABCG2 multidrug transporter directly from the plasma membrane. Biochim Biophys Act. 1808(1): 154-63 (2011)
  6. Sarkadi B, Homolya L, Szakács G, and Váradi A. Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system. Physiol Reviews 86: 1179-1236, (2006)
  7. Homolya L, Steinberg TH, and Boucher RC. Cell to cell communication in response to mechanical stress via bilateral release of ATP and UTP in polarized epithelia. Cell Biol., 150: 1349-1359, (2000)
  8. Homolya L, Watt CW, Lazarowski ER, Koller BH, and Boucher RC. Nucleotide-regulated calcium signaling in lung fibroblasts and epithelial cells from normal and P2Y2 receptor (-/-) mice. Biol. Chem., 274: 26454-26460 (1999)
  9. Lazarowski, E. R., Homolya, L., Boucher, R. C., and Harden, T. K.: Direct demonstration of mechanically induced release of UTP and its implication for uridine nucleotide receptor activation. Biol. Chem., 272: 24348-24354 (1997)
  10. Homolya L, Holló Zs, Germann U, Pastan I, Gottesman MM, and Sarkadi B. Fluorescent cellular indicators are extruded by the multidrug resistance protein. Biol. Chem., 268: 21493-21496 (1993)


Human Pluripotent Stem Cell Lab

Head of the laboratory: Ágota Apáti, Ph.D.

The Human Pluripotent Stem Cell lab has strong experience in human pluripotent stem cell generation and differentiation (especially in the direction of cardiac, neuronal, endothelial and mesenchymal cell types), in studying membrane transporters as well as calcium signalling. Recently they develop induced pluripotent stem cell-based disease models (such as schizophrenia, DiGeorge syndrome, arteriosclerosis, and type II diabetes), as well as transgenic cellular reporter systems.

Selected publications:

  1. Reé D, Borsy A, Fóthi Á, Orbán TI, Várady G, Erdei Z, Sarkadi B, Réthelyi J, Varga N, Apáti Á. Establishing a human embryonic stem cell clone with a heterozygous mutation in the DGCR8 gene. Stem Cell Res. 2020 Dec 22;50:102134. doi: 10.1016/j.scr.2020.102134. PMID: 33360445
  2. Szabó E, Juhász F, Hathy E, Reé D, Homolya L, Erdei Z, Réthelyi JM, Apáti Á. Functional Comparison of Blood-Derived Human Neural Progenitor Cells. Int J Mol Sci. 2020 Nov 30;21(23):9118. doi: 10.3390/ijms21239118. PMID: 33266139
  3. Hathy E, Szabó E, Varga N, Erdei Z, Tordai C, Czehlár B, Baradits M, Jezsó B, Koller J, Nagy L, Molnár MJ, Homolya L, Nemoda Z, Apáti Á, Réthelyi JM. Investigation of de novo mutations in a schizophrenia case-parent trio by induced pluripotent stem cell-based in vitro disease modeling: convergence of schizophrenia- and autism-related cellular phenotypes. Stem Cell Res Ther. 2020 Nov 27;11(1):504. doi: 10.1186/s13287-020-01980-5. PMID: 33246498
  4. Szabó E, Reé D, Jezsó B, Vincze K, Földes G, Molnár AÁ, Réthelyi JM, Apáti Á. Generation of iPSC lines from peripheral blood mononuclear cells of identical twins both suffering from type 2 diabetes mellitus and one of them additionally diagnosed with atherosclerosis. Stem Cell Res. 2020 Dec;49:102051. doi: 10.1016/j.scr.2020.102051. PMID: 33099106
  5. Berecz T, Husvéth-Tóth M, Mioulane M, Merkely B, Apáti Á, Földes G. Generation and Analysis of Pluripotent Stem Cell-Derived Cardiomyocytes and Endothelial Cells for High Content Screening Purposes. Methods Mol Biol. 2020;2150:57-77. doi: 10.1007/7651_2019_222. PMID: 30941720
  6. Erdei Z, Schamberger A, Török G, Szebényi K, Várady G, Orbán TI, Homolya L, Sarkadi B, Apáti Á. Generation of multidrug resistant human tissues by overexpression of the ABCG2 multidrug transporter in embryonic stem cells. PLoS One. 2018 Apr 12;13(4):e0194925. doi: 10.1371/journal.pone.0194925. eCollection 2018. PMID: 29649238
  7. Vőfély G, Berecz T, Szabó E, Szebényi K, Hathy E, Orbán TI, Sarkadi B, Homolya L, Marchetto MC, Réthelyi JM, Apáti Á. Characterization of calcium signals in human induced pluripotent stem cell-derived dentate gyrus neuronal progenitors and mature neurons, stably expressing an advanced calcium indicator protein. Mol Cell Neurosci. 2018 Apr;88:222-230. doi: 10.1016/j.mcn.2018.02.003. PMID: 29425968
  8. 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 Kidney Proximal Tubules. J Am Soc Nephrol. 2015 Nov;26(11):2731-40. doi: 10.1681/ASN.2014070705. PMID: 25788535
  9. Bacskai I, Mázló A, Kis-Tóth K, Szabó A, Panyi G, Sarkadi B, Apáti Á, Rajnavölgyi É. Mesenchymal Stromal Cell-Like Cells Set the Balance of Stimulatory and Inhibitory Signals in Monocyte-Derived Dendritic Cells. Stem Cells Dev. 2015 Aug 1;24(15):1805-16. doi: 10.1089/scd.2014.0509. Epub 2015 Apr 29. PMID: 25808140
  10. Apáti A, Orbán TI, Varga N, Németh A, Schamberger A, Krizsik V, Erdélyi-Belle B, Homolya L, Várady G, Padányi R, Karászi E, Kemna EW, Német K, Sarkadi B. High level functional expression of the ABCG2 multidrug transporter in undifferentiated human embryonic stem cells. Biochim Biophys Acta. 2008 Dec;1778(12):2700-9. doi: 10.1016/j.bbamem.2008.08.010. PMID: 18793608


Flow Cytometry Lab

Head of the laboratory: György Várady, Ph.D.

The Flow Cytometry lab serves as a core facility and research laboratory. Our cell sorter allows us to generate single cell clones and homogeneous cell lines based on the cellular fluorescence intensities. In addition, cytometers are used for the assessment of protein levels, transfection efficiency, and multidrug resistance, as well as for cell cycle analysis. Our main research area includes the functional investigation of ABC transporters using fluorescent dyes and the characterization of multifactorial diseases (gout, type 2 diabetes) by the analysis of the membrane proteins in red blood cells.

Main instruments:

FACSAria III cell sorter;

Attune Nxt with 3 (viola, blue, red) and 4 (viola, blue, yellow, red) lasers and plate reader;

FACSCanto II with 3 (viola, blue, red) lasers with plate reader

Selected publications:

  1. Szabó E, Kulin A, Korányi L; Literáti-Nagy B, Cserepes J, Somogyi A, Sarkadi B, and Várady G. Alterations in erythrocyte membrane transporter expression levels in type 2 diabetic patients Sci Rep. 11(1):2765 (2021)
  2. Telbisz Á, Ambrus Cs, Mózner O, Szabó E, Várady Gy, Bakos É, Sarkadi B, Özvegy-Laczka Cs. Interactions of Potential Anti-COVID-19 Compounds with Multispecific ABC and OATP Drug Transporters Pharmaceutics 13 (1) 81 (2021)
  3. Kovacsics D, Brózik A, Tihanyi B, Matula Zs, Borsy A, Mészáros N, Szabó E, Németh E, Fóthi Á, Zámbó B, Szüts D, Várady Gy, Orbán T I, Apáti Á, Sarkadi B. Precision-engineered reporter cell lines reveal ABCG2 regulation in live lung cancer cells Biochemical Pharmacology 175: 113865 (2020)
  4. Zámbó B, Bartos Z, Mózner O, Szabó E, Várady Gy, Poór Gy, Pálinkás M, Andrikovics H, Hegedűs T, Homolya L, Sarkadi B. Clinically relevant mutations in the ABCG2 transporter uncovered by genetic analysis linked to erythrocyte membrane protein expression Sci Rep. 8(1): 7487 (2018)
  5. Szabó E, Türk D, Telbisz Á, Kucsma N, Horváth T, Szakács G, Homolya L, Sarkadi B, Várady Gy. A new fluorescent dye accumulation assay for parallel measurements of the ABCG2, ABCB1 and ABCC1 multidrug transporter functions Plos One 13(1): e0190629 (2018)
  6. Zámbó B, Várady Gy, Padányi R, Szabó E, Németh A, Langó T, Enyedi Á, Sarkadi B. Decreased calcium pump expression in human erythrocytes is connected to a minor haplotype in the ATP2B4 gene Cell Calcium 65. 73 (2017)
  7. Várady Gy, Szabó E, Fehér Á, Németh A, Zámbó B, Pákáski M, Janka Z, Sarkadi B. Alterations of membrane protein expression in red blood cells of Alzheimer’s disease patients Alzheimers & Dementia: Diagnosis Assessment & Disease Monitoring 1(3) 334 (2015)


László Homolya