Informace o projektu
Coding and Non-coding RNA Networks that Regulate B Cell Receptor Signalling: Implications for Combinatorial Therapy
- Kód projektu
- MUNI/H/0865/2016
- Období řešení
- 2/2017 - 12/2019
- Investor / Programový rámec / typ projektu
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Masarykova univerzita
- Grantová agentura MU
- Individuální projekty hraničního výzkumu
- Fakulta / Pracoviště MU
- Středoevropský technologický institut
The approval of drugs that target the B cell receptor pathway (BCR) is an important step in the treatment of chronic lymphocytic leukaemia (CLL). However, the use of these novel drugs still does not lead to a cure and the patients relapse. The key question is how to combine BCR inhibitors with other drugs to achieve a cure or the “permanent” control of the disease. The design of smart combinatorial treatment of BCR-inhibitors requires gaining a full understanding of coding and non-coding RNA networks in B cells with inhibited BCR signalling. This proposal will take advantage of the possibility to analyse gene expression (Illumina) from primary B cells obtained directly from CLL patients both before and during the administration of BCR-inhibitors.
Objectives: i) To decipher how miRNAs and other non-coding RNAs regulate the BCR pathway in the context of microenvironmental interactions. These observations will likely be transferred to other B cell diseases and normal B cells. ii) To define the role of miRNAs in the regulation of BCR signalling in response to DNA damage, whose deregulation is associated with early relapses in BCR-inhibitors. The mechanisms that stop the pro-proliferative and anti-apoptotic signals from BCR after DNA damage are not yet known. iii) To use the knowledge of gene regulatory networks to reveal molecular inhibitors that should be used clinically in combination with BCRinhibitors. BCR-inhibitors are a very expensive (~€ 7 000/month) non-curative treatment, and there is a need for their combination with other drugs to achieve better disease control. The proposal has been previously submitted as a StartUp ERC grant and received very favourable comments (see below), however it was not funded. I aim to demonstrate that our approaches are feasible, novel, and improve the application by additional preliminary data to successfully re-apply for the ERC grant.
Publikace
Počet publikací: 12
2019
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B Cell Receptor Signalling Regulation by Non-coding RNAs.
Rok: 2019, druh: Konferenční abstrakty
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CD20 in the context of microenvironmental interactions of malignant B cells: Implications for targeted therapy.
Rok: 2019, druh: Konferenční abstrakty
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Mechanism of leukemia cell adaptation to targeted therapy in chronic lymphocytic leukemia
Rok: 2019, druh: Konferenční abstrakty
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Regulation of B Cell Receptor signalling in B cell leukemias: novel mechanisms and therapeutic implications.
Rok: 2019, druh: Konferenční abstrakty
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The surprising role of microRNAs in the DNA damage and B cell receptor signalling in malignant B cells
Rok: 2019, druh: Konferenční abstrakty
2018
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CD20 is a direct regulator of B-cell receptor signaling in the microenvironment of chronic lymphocytic leukemia
Rok: 2018, druh: Konferenční abstrakty
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CD20 reguluje signalizaci přes B-buněčný receptor v mikroprostředí chronické lymfocytární leukémie
Rok: 2018, druh: Konferenční abstrakty
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CD20 supports BCR signaling in an intra clonal aggressive chronic lymphocytic leukemia subpopulation of cells and rituximab primarily targets these BCR proficient B cells in vivo
Rok: 2018, druh: Konferenční abstrakty
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MYC-mediated downregulation of miR-150 contributes to the transformation of follicular lymphoma by upregulating FOXP1 levels
Rok: 2018, druh: Konferenční abstrakty
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MYC-mediated downregulation of miR-150 contributes to the transformation of follicular lymphoma to DLBCL by upregulating FOXP1 levels
Rok: 2018, druh: Konferenční abstrakty