Our goal is to understand mechanisms of resistance and discover potential molecular targets in leukemia to develop and propose novel therapies, with special interest in intercellular interactions and their role within the leukemia microenvironment.
We focus on investigation of the cytoprotective pathways, stress response and DNA repair mechanisms in order to propose and verify novel prospective targets and potential therapeutic treatments, including personalized therapies. A high priority is to understand the intercellular cross-talk between the leukemic and surrounding cells and the role of leukemia microenvironment - bone marrow stroma or immune system cells in development of disease and resistance.
We realize these aims in in vitro and in vivo models by studies at the genomic, proteomic and cellular levels, together with a diverse array of techniques, ranging from biochemical and molecular biology methods to cellular biology, cytometry and microscopy techniques, including confocal, EM, SEM, light sheet, superresolution and spinning disc microscopy to visualize cellular processes and molecules.
Currently we investigate:
· Integrated Stress Response pathways in leukemia
· Non-classical mechanisms of BRCA1/2 deficiencies in leukemia and sensitivity to personalized therapy by PARP inhibitors
· The leukemia-bone marrow stroma interactions
· Direct intercellular connections within leukemia microenvironment by tunneling nanotubes (TNTs)
· Leukemic extracellular vesicles and influence on immunosuppression
· Protein markers for BRCA1/2 deficiency and PARP1 inhibitors in cancer
Szymańska E, Nowak P, Kolmus K, Cybulska M, Goryca K, Derezińska-Wołek E, Szumera-Ciećkiewicz A, Brewińska-Olchowik M, Grochowska A, Piwocka K, Prochorec-Sobieszek M, Mikula M, Miączyńska M. Synthetic lethality between VPS4A and VPS4B triggers an inflammatory response in colorectal cancer. EMBO Mol Med. 2020 Jan 13:e10812. doi: 10.15252/emmm.201910812. [Epub ahead of print] PubMed PMID: 31930723.
Swatler J, Dudka W, Bugajski L, Brewinska-Olchowik M, Kozlowska E, Piwocka K. Chronic myeloid leukemia-derived extracellular vesicles increase Foxp3 level and suppressive activity of thymic regulatory T cells. Eur J Immunol. 2019 Nov 23. doi: 10.1002/eji.201848051. [Epub ahead of print] PubMed PMID: 31758697.
Kolba MD, Dudka W, Zaręba-Kozioł M, Kominek A, Ronchi P, Turos L, Chroscicki P, Wlodarczyk J, Schwab Y, Klejman A, Cysewski D, Srpan K, Davis DM, Piwocka K. Tunneling nanotube-mediated intercellular vesicle and protein transfer in the stroma-provided imatinib resistance in chronic myeloid leukemia cells. Cell Death Dis. 2019 Oct 28;10(11):817. doi: 10.1038/s41419-019-2045-8. PubMed PMID: 31659149; PubMed Central PMCID: PMC6817823.
Świerczek-Lasek B, Neska J, Kominek A, Tolak Ł, Czajkowski T, Jańczyk-Ilach K, Stremińska W, Piwocka K, Ciemerych MA, Archacka K. Interleukin 4 Moderately Affects Competence of Pluripotent Stem Cells for Myogenic Conversion. Int J Mol Sci. 2019 Aug 13;20(16). pii: E3932. doi: 10.3390/ijms20163932. PubMed PMID: 31412558; PubMed Central PMCID: PMC6720909.
Fedorczyk B, Lipiński PFJ, Puszko AK, Tymecka D, Wilenska B, Dudka W, Perret GY, Wieczorek R, Misicka A. Triazolopeptides Inhibiting the Interaction between Neuropilin-1 and Vascular Endothelial Growth Factor-165. Molecules. 2019 May 6;24(9). pii: E1756. doi: 10.3390/molecules24091756. PubMed PMID: 31064153; PubMed Central PMCID: PMC6539594.
Pawlak M, Kedzierska KZ, Migdal M, Nahia KA, Ramilowski JA, Bugajski L, Hashimoto K, Marconi A, Piwocka K, Carninci P, Winata CL. Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development. Genome Res. 2019 Mar;29(3):506-519. doi: 10.1101/gr.244491.118. Epub 2019 Feb 13. PubMed PMID: 30760547; PubMed Central PMCID: PMC6396412.
For more go to Publications