RESEARCH GROUP

Cellular and Molecular Immunoregulation (CMI)

PRINCIPAL INVESTIGATOR

KEY INTERESTSInduced Pluripotent Stem Cell • Mesenchymal Stem Cell • Myeloid Hematopoiesis • Toll Like Receptors • Pattern Recognition Receptors • Immunosuppression • Chronic Inflammation

RESEARCH OBJECTIVES Description of the role of pattern recognition receptors and their ligands in tissue regeneration.

Functional analysis of induced pluripotent stem cells derived myeloid cells. Set up in vitro models mimicking physiological immune system interaction with the surrounding milieu, tissue-specific cells and mesenchymal stem cells.

RESEARCH FOCUSThe Cellular and Molecular Immunoregulation group is determined to dissect cell signaling, which controls innate immune response. CMI develops experimental models addressing the role of hematopoietic precursors and mesenchymal stem cells in orchestrating immune response and tissue regeneration. Furthermore, CMI studies unresolved aspects of pattern recognition receptors (including Toll-like receptors) signaling pathways in peripheral blood monocytes. These signaling pathways are main sensors of infection and tissue damage and play crucial role in control of acute and chronic inflammatory disorders accompanying for example tissue regeneration or ageing processes. Better understanding of pattern recognition receptors signaling may lead to new strategies for therapeutic control of inflammatory disorders.

ST. ANNE‘S UNIVERSITY HOSPITAL BRNOINTERNATIONAL CLINICAL RESEARCH CENTER

Mgr. Jan FRIČ, Ph.D.

E-mail: jan.fric@fnusa.czPhone: (+420) 543 185 525

CREATING THE FUTURE OF MEDICINE

EDUCATION

2008: Ph.D. in Immunology, Charles University, Prague, Czech Republic

2000: Mgr./MSc. in Biology – Immunology, Charles University, Prague, Czech Republic

TRAINING

2008-2015: Senior Research Fellow and Research Scientist; Immunology, Innate Immune Response, Stem Cell Biology and Cell Signaling; Singapore Immunology Network; Agency for Science, Technology and Research, Singapore

CARDIO NEURO TRANSLATIONAL MEDICINE

BIOMOLECULAR AND CELLULAR ENGINEERING

RESEARCH FACILITIES

TOP PUBLICATIONS

MAIN PARTNERS AND COLLABORATING INSTITUTIONS Singapore Immunology Network, Singapore University of Perugia, Perugia, Italy Charles University in Prague, Prague, Czech Republic

OFFERED SERVICES AND EXPERTISE FACS sorting of cells using MoFlo. Multiparametric FACS analysis. Histology and imaging techniques.

BEST RESULTS The CMI has published series of papers (Mucosal Immunology, Cell Reports, Stem Cells, EMBO Molecular Medicine and Blood) showing new important mechanism of immune protection against pathogens and myeloid cells development.

The CMI has shown that immunosuppressive drugs (such as Cyclosporine A or Tacrolimus) affect function of calcineurin NFAT signaling pathway in myeloid cells and their precursors, which causes dysregulation of myelopoiesis and increased susceptibility to infections. These results are important for understanding the complications of immunosuppressive therapies.

ZELANTE, T., WONG, A., MENCARELLI, A., FOO, S., ZOLEZZI, F., LEE, B., POIDINGER, M., RICCIARDI-CASTAGNOLI, P., FRIČ, J. Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis. Mucosal Immunology. 2016 [E-pub ahead of print]

ZELANTE, T., WONG, A., PING, T., CHEN, J., SUMATOH, H., VIGANÒ, E., HONG BING, Y., LEE, B., ZOLEZZI, F., FRIČ, J., NEWELL, E., MORTELLARO, A., POIDINGER, M., PUCCETTI, P., RICCIARDI-CASTAGNOLI, P. CD103(+) Dendritic Cells Control Th17 Cell Function in the Lung. Cell Reports. 2015, 12(11), 1789-1801.

FRIC, J., LIM, CX., MERTES, A., LEE, B., VIGANÒ, E., CHEN, J., ZOLEZZI, F., POIDINGER, M., LARBI, A., STROBL, H., ZELANTE, T., RICCIARDI-CASTAGNOLI, P. Calcium and calcineurin-NFAT signaling regulate granulocyte-monocyte progenitor cell cycle via Flt3-L. Stem Cells. 2014, 32(12), 3232-44.

FRIC, J., T. ZELANTE, A. Y. W. WONG, A. MERTES, et al. NFAT control of innate immunity. Blood. 2012, 120(7), 1380-1389.

PADUA, R. A., J. LARGHERO, M. ROBIN, C. LE POGAM, et al. PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia. Nature Medicine. 2003, 9(11), 1413-1417.

St. Anne‘s University Hospital BrnoInternational Clinical Research Center

Pekařská 53, 656 91 Brno | Czech Republic | ID: 00159816Phone: (+420) 543 181 111 | E-mail: icrc@fnusa.cz | www.fnusa-icrc.org

TRANSLATIONAL MEDICINETranslating Basic Mechanisms of Development of Disease into Clinical Practice and Vice Versa

Supported by the project no. LQ1605 Translational Medicine from the National Program of Sustainability II (MEYS CR)

TECHNOLOGICAL EQUIPMENT Flow Cytometry Facility - mastering the complexity of cell isolation:

▪ Flow Cytometer (FACSCanto) - multiparametric analysis of cell phenotype (up to 8 fluorescence markers).

▪ Cell Sorter (MoFlo Astrios) - high speed cell sorting with 14 fluorescence detectors).▪ Magnetic Cell Separator (AutoMACS, Miltenyi) - automatic and fast high purity

enrichment of cell subsets. Multiphoton Microscope - analysis of full thickness tissues explants and 3D cultures. Confocal Laser Scanning Microscope suited for live imaging. Laser Microdissection Microscope with PALM mircobeam system. PCR and Real-Time PCR System - gene expression analysis, ELISA, ELISPOT.