Stem Cell Differentiation Laboratory

Department of Biochemistry and Molecular Biology
Faculty of Medicine
University of Debrecen
Life Science Building

 
Egyetem tér 1.
Debrecen, Hungary, H-4010
Phone: +36-52-416-432
Direct dial:
+36-52-512-900 ext. 65527 (office); 62444 or 64593 (lab)
Fax: +36-52-314-989

GROUP MEMBERS

CURRENT RESEARCH

Dendritic cells (DCs) are professional antigen presenting cells that are specialized to capture, process and present antigens to T cells in order to modulate immune response. The use of DCs to prime responses to tumor antigens provides a promising approach to cancer immunotherapy but clinically relevant responses have frequently been disappointing. Newer generation DC vaccines must build on the increased knowledge of DC differentiation including the generation of various DC subsets ex vivo. DC development is regulated by a few cytokines (Flt3L, GM-CSF, M-CSF, IL-4), thus we have limited tools to modulate the lineage specification of these cell types ex vivo. Cytokines modulate cell fate specification through the actions of transcription factors. Of note, several transcription factors have been recently identified which control the specification and development of dendritic cells.

The primary research focus of our group is to generate DCs from pluripotent stem cells and modify the transcription program of these cells via perturbing the expression of lineage determining transcription factors. Our long-term goal is to control the myeloid blood cell development by transcription factor mediated cellular programming. We also intend to perform global gene expression studies to compare the expression profile of myeloid cells during the various stages of development. Moreover, we propose to perform chromatin immunoprecipitation followed by sequencing (ChIP-seq) to identify the global list of DNA binding sites of DC specific transcription factors in myeloid cells.

RESEARCH INFRASTRUCTURE

Special instruments and tools:

BD FACS Aria III flow cytometer and cell sorter

Neon Transfection System

EVOS Digital Inverted Brightfield and Phase Contrast Microscope

EVOS FLoid Cell Imaging Station Fluorescence Microscope

Countess Automated Cell Counter

SELECTED PUBLICATIONS

Nagy L, Szanto A, Szatmari I, Széles L. 2012. Nuclear hormone receptors enable macrophages and dendritic cells to sense their lipid environment and shape their immune response. Physiol Rev. 92(2):739-89.

Iacovino M, Chong D, Szatmari I, Hartweck L, Rux D, Caprioli A, Cleaver O and Kyba M. 2011. HoxA3 is an apical regulator of haemogenic endothelium. Nature Cell Biol. 13(1):72-8.

Szatmari I, Iacovino M, Kyba M. 2010. The retinoid signaling pathway inhibits hematopoiesis and uncouples from the Hox genes during hematopoietic development. Stem Cells. 28:1518-29.

Szatmari, I. and Nagy, L. 2008. Nuclear receptor signalling in dendritic cells connects lipids, the genome and immune function. EMBO J 27:2353-2362.

Szatmari, I., Torocsik, D., Agostini, M., Nagy, T., Gurnell, M., Barta, E., Chatterjee, K. and Nagy, L. 2007. PPAR{gamma} regulates the function of human dendritic cells primarily by altering lipid metabolism. Blood 110:3271-3280.

Agostini, M., E. Schoenmakers, C. Mitchell, I. Szatmari, D. Savage, A. Smith, O. Rajanayagam, R. Semple, J. Luan, L. Bath, A. Zalin, M. Labib, S. Kumar, H. Simpson, D. Blom, D. Marais, J. Schwabe, I. Barroso, R. Trembath, N. Wareham, L. Nagy, M. Gurnell, S. O'Rahilly, and K. Chatterjee. 2006. Non-DNA binding, dominant-negative, human PPARgamma mutations cause lipodystrophic insulin resistance. Cell Metab 4:303-311.

Szatmari, I., A. Pap, R. Ruhl, J.X. Ma, P.A. Illarionov, G.S. Besra, E. Rajnavolgyi, B. Dezso, and L. Nagy. 2006. PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med 203:2351-2362.

Szatmari, I., G. Vamosi, P. Brazda, B.L. Balint, S. Benko, L. Szeles, V. Jeney, C. Ozvegy-Laczka, A. Szanto, E. Barta, J. Balla, B. Sarkadi, and L. Nagy. 2006. Peroxisome proliferator-activated receptor gamma-regulated ABCG2 expression confers cytoprotection to human dendritic cells. J Biol Chem 281:23812-23823.

Szatmari, I., P. Gogolak, J.S. Im, B. Dezso, E. Rajnavolgyi, and L. Nagy. 2004. Activation of PPARgamma specifies a dendritic cell subtype capable of enhanced induction of iNKT cell expansion. Immunity 21:95-106.

Szatmari, I., and J. Aradi. 2001. Telomeric repeat amplification, without shortening or lengthening of the telomerase products: a method to analyze the processivity of telomerase enzyme. Nucleic Acids Res 29:E3.