Projects & Grants
The HRS4R human resources management strategy for the scientific sector was funded through the project „HR Excellence in Research na Ostravské univerzitě“, Reg. No.: CZ.02.2.69/0.0/0.0/16_028/0006225.
| Epigenetic Rewiring in Extramedullary Multiple Myeloma: Clinical Implications and Novel Therapeutic Targets | |
|---|---|
| Project Id | NW27J-03-00121 |
| Main solver | Mgr. David Žihala, Ph.D. |
| Period | 1/2027 - 12/2030 |
| Provider | Agentura zdravotnického výzkumu ČR |
| State | solved |
| Anotation | Extramedullary multiple myeloma (EMM) is an aggressive and treatment-resistant form of multiple myeloma associated with a very poor prognosis and limited therapeutic options. Our preliminary data indicate that EMM progression is driven by extensive epigenetic reprogramming, leading to reduced expression of key receptors responsible for bone marrow homing (CXCR4) and therapeutic targets (CD38, GPRC5D), along with increased expression of proliferative long non-coding RNAs, including EPIC1. In this project, we will characterize reversible epigenetic changes and lncRNA alterations underlying EMM dissemination and treatment resistance, and functionally validate key epigenetic regulators, including EZH2 and DNA methyltransferases (DNMTs), as therapeutic targets. We will employ an integrated multi-omics approach combining RNA sequencing (RNA-seq), ATAC-seq, and whole-exome sequencing (WES) using primary patient samples (N = 30 per group: EMM, newly diagnosed, and relapsed/refractory multiple myeloma). Functional validation will be performed in primary EMM cells and in iPSC-derived bone marrow models. We will experimentally evaluate the effects of clinically available EZH2 and DNMT inhibitors on restoring the expression of therapeutically relevant targets (e.g., CD38 and GPRC5D) and on suppressing tumor cell proliferation and dissemination. By targeting reversible epigenetic mechanisms, the project will provide a rational basis for integrating epigenetic therapy into current EMM treatment strategies and support the design of clinical trials investigating such combinations in EMM. |
| Total Costs | 8 488 000 CZK |
