Microenvironment of Immune Cells
Head: Marek Mráz
Brno node
HOME INSTITUTION
CEITEC MU
RESEARCH PROGRAMME(S)
RP 1 - Molecular basis of cancer and molecular targets
RP 3 - Biomarkers of cancers and cancer diagnostics
Some tumours are completely dependent on their microenvironment.
- Mission: Studying the role of the microenvironment in the development and aggressiveness of B cell malignancies.
- Vision: Use knowledge of the biology of B-cell malignancies to develop therapeutic strategies that do not involve chemotherapy and lead to durable disease control/cure.
Main projects:
1. Microenvironmental interactions in normal and malignant immune cells
The microenvironment of immune niches plays an important role in the onset, progression, and resistance of hematological malignancies. We largely focus on the role of non-coding RNAs (especially microRNAs [miRNAs]) in these pathways. We also study the regulation and function of a cell-surface molecule CD20 in this context, since this molecule is used as a therapeutic target for over 20 years, but its regulation and function is unclear.
SELECTED PUBLICATIONS
- Seda V, Vojackova E, Ondrisova L, Kostalova L, Sharma S, Loja T, Pavlasova G, …..Tan Z, Zhang S, Doubek M, Cerna K, Mayer J, Mraz M. FoxO1-GAB1 Axis Regulates Homing Capacity and Tonic AKT Activity in Chronic Lymphocytic Leukemia. Blood. 2021 Sep 2;138(9):758-772. DOI: 10.1182/blood.2020008101
- Sharma S, Pavlasova GM, Seda V, Cerna KA, Vojackova E, Filip D, Ondrisova L, Sandova V, Kostalova L, Zeni PF, Borsky M, Oppelt J, Liskova K, Kren L, Janikova A, Pospisilova S, Fernandes SM, Shehata M, Rassenti LZ, Jaeger U, Doubek M, Davids MS, Brown JR, Mayer J, Kipps TJ, Mraz M. miR-29 Modulates CD40 Signaling in Chronic Lymphocytic Leukemia by Targeting TRAF4: an Axis Affected by BCR inhibitors. Blood. 2021 May 6;137(18):2481-24942020. DOI: 10.1182/blood.2020005627
- Sandova V, Pavlasova GM, Seda V, Cerna KA, Sharma S, Palusova V, Brychtova Y, Pospisilova S, Fernandes SM, Panovska A, Doubek M, Davids MS, Brown JR, Mayer J, Mraz M. IL4-STAT6 signaling induces CD20 in chronic lymphocytic leukemia and this axis is repressed by PI3Kδ inhibitor idelalisib. Haematologica. 2021 Nov 1;106(11):2995-2999. DOI: 10.3324/haematol.2021.278644
- Musilova K, Devan J, Cerna K, Seda V, Pavlasova G, Sharma S, Oppelt J, Pytlik R, Prochazka V, …. Trneny M, Evans AG, Janikova A, Mraz M. miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels. Blood. 2018 Nov 29;132(22):2389-2400. DOI: 10.1182/blood-2018-06-855502
- Cerna K, Oppelt J, Chochola V, Musilova K, Seda V, Pavlasova G, Radova L, Arigoni M, Calogero RA, Benes V, Trbusek M, Brychtova Y, Doubek M, Mayer J, Pospisilova S, Mraz M. MicroRNA miR-34a downregulates FOXP1 during DNA damage response to limit BCR signalling in chronic lymphocytic leukaemia B cells. Leukemia. 2019 Feb;33(2):403-414. DOI: 10.1038/s41375-018-0230-x
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Hoferkova E, Seda V, Kadakova S, Verner J, Loja T, Matulova K, Skuhrova Francova H, Ondrouskova E, Filip D, Blavet N, Boudny M, Mladonicka Pavlasova G, Vecera J, Ondrisova L, Pavelkova P, Hlavac K, Kostalova L, Michaelou A, Pospisilova S, Dorazilova J, Chochola V, Jaros J, Doubek M, Jarosova M, Hampl A, Vojtova L, Kren L, Mayer J, Mraz M. Stromal cells engineered to express T cell factors induce robust CLL cell proliferation in vitro and in PDX co-transplantations allowing the identification of RAF inhibitors as anti-proliferative drugs. Leukemia. 2024 Jun 14. DOI: 10.1038/s41375-024-02284-w
COLLABORATION WITHIN THE NICR
Jiří Mayer
(Brno node, Faculty of Medicine MU)
Pavel Klener
(Prague node, First Faculty of Medicine CU)
Šárka Pospíšilová
(Brno node, Faculty of Medicine MU/CEITEC MU)
Vítězslav Bryja
(Brno node, Faculty of Science MU)
SPECIALIZED EXPERTISE AND TECHNOLOGY
2D/3D models of microenvironmental interactions in B malignancies
Studying the role of ncRNAs (miRNAs/lncRNA)
Drug testing on primary samples