Research
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
Recent publications:
2024
Rudzinska-Radecka M, Turos-Korgul L, Mukherjee D, Podszywalow-Bartnicka P, Piwocka K, Guzowski J. High-throughput formulation of reproducible 3D cancer microenvironments for drug testing in myeloid leukemia. Biofabrication. 2024 Dec 2. doi: 10.1088/1758-5090/ad998d. Epub ahead of print. PMID: 39622161.
Swatler J, Targońska A, Turos-Korgul L, Mosieniak G, Piwocka K. Protocol for isolation of tumor-derived extracellular vesicles and functional studies on human T cell subsets. STAR Protoc. 2024 Jun 21;5(2):103011. doi: 10.1016/j.xpro.2024.103011. Epub 2024 Apr 12. PMID: 38613780; PMCID: PMC11026832.
De Biasi S, Gigan JP, Borella R, Santacroce E, Lo Tartaro D, Neroni A, Paschalidis N, Piwocka K, Argüello RJ, Gibellini L, Cossarizza A. Cell metabolism: Functional and phenotypic single cell approaches. Methods Cell Biol. 2024;186:151-187. doi: 10.1016/bs.mcb.2024.02.024. Epub 2024 Mar 25. PMID: 38705598.
Smolinska A, Chodkowska M, Kominek A, Janiec J, Piwocka K, Sulejczak D, Sarnowska A. Stemness properties of SSEA-4+ subpopulation isolated from heterogenous Wharton's jelly mesenchymal stem/stromal cells. Front Cell Dev Biol. 2024 Feb 22;12:1227034. doi: 10.3389/fcell.2024.1227034. PMID: 38455073; PMCID: PMC10917976.
Zurawska G, Jończy A, Niklewicz M, Sas Z, Rumieńczyk I, Kulecka M, Piwocka K, Rygiel TP, Mikula M, Mleczko-Sanecka K. Iron-triggered signaling via ETS1 and the p38/JNK MAPK pathway regulates Bmp6 expression. Am J Hematol. 2024 Jan 31. doi: 10.1002/ajh.27223. Epub ahead of print. PMID: 38293789.
2023
Vekariya U, Toma M, Nieborowska-Skorska M, Le BV, Caron MC, Kukuyan AM, Sullivan-Reed K, Podszywalow-Bartnicka P, Chitrala KN, Atkins J, Drzewiecka M, Feng W, Chan J, Chatla S, Golovine K, Jelinek J, Sliwinski T, Ghosh J, Matlawska-Wasowska K, Chandramouly G, Nejati R, Wasik M, Sykes SM, Piwocka K, Hadzijusufovic E, Valent P, Pomerantz RT, Morton G, Childers W, Zhao H, Paietta EM, Levine RL, Tallman MS, Fernandez HF, Litzow MR, Gupta GP, Masson JY, Skorski T. DNA polymerase θ protects leukemia cells from metabolically induced DNA damage. Blood. 2023 May 11;141(19):2372-2389. doi: 10.1182/blood.2022018428. PMID: 36580665; PMCID: PMC10273171.
Wolczyk M, Serwa R, Kominek A, Klejman A, Milek J, Chwałek M, Turos-Korgul L, Charzyńska A, Dabrowski M, Dziembowska M, Skorski T, Piwocka K, Podszywalow-Bartnicka P. TIAR and FMRP shape pro-survival nascent proteome of leukemia cells in the bone marrow microenvironment. iScience. 2023 Mar 31;26(4):106543. doi: 10.1016/j.isci.2023.106543. PMID: 37123244; PMCID: PMC10140000.
Synowiec A, Brodaczewska K, Wcisło G, Majewska A, Borkowska A, Filipiak-Duliban A, Gawrylak A, Wilkus K, Piwocka K, Kominek A, Waś H, Lewicki S, Siewiera J, Szczylik C, Szenajch J, Kubiak JZ, Kieda C. Hypoxia, but Not Normoxia, Reduces Effects of Resveratrol on Cisplatin Treatment in A2780 Ovarian Cancer Cells: A Challenge for Resveratrol Use in Anticancer Adjuvant Cisplatin Therapy. Int J Mol Sci. 2023 Mar 16;24(6):5715. doi: 10.3390/ijms24065715. PMID: 36982788; PMCID: PMC10051682.
Swatler J, Lo Tartaro D, Borella R, Brewinska-Olchowik M, Paolini A, Neroni A, Turos-Korgul L, Wiech M, Kozlowska E, Cysewski D, Grabowska-Pyrzewicz W, Wojda U, Basak G, Argüello RJ, Cossarizza A, De Biasi S, Piwocka K. Dysfunctional subsets of CD39+ T cells, distinct from PD-1+, driven by leukemic extracellular vesicles in myeloid leukemias. Haematologica. 2023 Mar 1;108(3):909-916. doi: 10.3324/haematol.2022.281713. PMID: 36384249; PMCID: PMC9973468.
Lo Tartaro D, Paolini A, Mattioli M, Swatler J, Neroni A, Borella R, Santacroce E, Di Nella A, Gozzi L, Busani S, Cuccorese M, Trenti T, Meschiari M, Guaraldi G, Girardis M, Mussini C, Piwocka K, Gibellini L, Cossarizza A, De Biasi S. Detailed characterization of SARS-CoV-2-specific T and B cells after infection or heterologous vaccination. Front Immunol. 2023 Feb 9;14:1123724. doi: 10.3389/fimmu.2023.1123724. PMID: 36845156; PMCID: PMC9947839.
2022
Dudka W, Hoser G, Mondal SS, Turos-Korgul L, Swatler J, Kusio-Kobialka M, Wołczyk M, Klejman A, Brewinska-Olchowik M, Kominek A, Wiech M, Machnicki MM, Seferynska I, Stoklosa T, Piwocka K. Targeting integrated stress response with ISRIB combined with imatinib treatment attenuates RAS/RAF/MAPK and STAT5 signaling and eradicates chronic myeloid leukemia cells. BMC Cancer. 2022 Dec 2;22(1):1254. doi: 10.1186/s12885-022-10289-w. PMID: 36460969; PMCID: PMC9719211.
Le BV, Podszywałow-Bartnicka P, Piwocka K, Skorski T. Pre-Existing and Acquired Resistance to PARP Inhibitor-Induced Synthetic Lethality. Cancers (Basel). 2022 Nov 24;14(23):5795. doi: 10.3390/cancers14235795. PMID: 36497275; PMCID: PMC9741207.
Głuchowska A, Cysewski D, Baj-Krzyworzeka M, Szatanek R, Węglarczyk K, Podszywałow-Bartnicka P, Sunderland P, Kozłowska E, Śliwińska MA, Dąbrowski M, Sikora E, Mosieniak G. Unbiased proteomic analysis of extracellular vesicles secreted by senescent human vascular smooth muscle cells reveals their ability to modulate immune cell functions. Geroscience. 2022 Jul 28. doi: 10.1007/s11357-022-00625-0. Epub ahead of print. PMID: 35900662.
Turos-Korgul L, Kolba MD, Chroscicki P, Zieminska A, Piwocka K. Tunneling Nanotubes Facilitate Intercellular Protein Transfer and Cell Networks Function. Front Cell Dev Biol. 2022 Jul 12;10:915117. doi: 10.3389/fcell.2022.915117. PMID: 35903550; PMCID: PMC9314668.
Wiech M, Chroscicki P, Swatler J, Stepnik D, De Biasi S, Hampel M, Brewinska-Olchowik M, Maliszewska A, Sklinda K, Durlik M, Wierzba W, Cossarizza A, Piwocka K. Remodeling of T Cell Dynamics During Long COVID Is Dependent on Severity of SARS-CoV-2 Infection. Front Immunol. 2022 Jun 10;13:886431. doi: 10.3389/fimmu.2022.886431. PMID: 35757700; PMCID: PMC9226563.
Swatler J, Turos-Korgul L, Brewinska-Olchowik M, De Biasi S, Dudka W, Le BV, Kominek A, Cyranowski S, Pilanc P, Mohammadi E, Cysewski D, Kozlowska E, Grabowska-Pyrzewicz W, Wojda U, Basak G, Mieczkowski J, Skorski T, Cossarizza A, Piwocka K. 4-1BBL-containing leukemic extracellular vesicles promote immunosuppressive effector regulatory T cells. Blood Adv. 2022 Mar 22;6(6):1879-1894. doi: 10.1182/bloodadvances.2021006195. PMID: 35130345; PMCID: PMC8941461.
2021
Migdał M, Tralle E, Nahia KA, Bugajski Ł, Kędzierska KZ, Garbicz F, Piwocka K, Winata CL, Pawlak M. Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift. BMC Genomics. 2021 Dec 18;22(1):904. doi: 10.1186/s12864-021-08173-1. PMID: 34920711; PMCID: PMC8684102.
Abu Nahia K, Migdał M, Quinn TA, Poon KL, Łapiński M, Sulej A, Liu J, Mondal SS, Pawlak M, Bugajski Ł, Piwocka K, Brand T, Kohl P, Korzh V, Winata C. Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region. Cell Mol Life Sci. 2021 Oct;78(19-20):6669-6687. doi: 10.1007/s00018-021-03939-y. Epub 2021 Sep 23. PMID: 34557935; PMCID: PMC8558220.
Świerczek-Lasek B, Dudka D, Bauer D, Czajkowski T, Ilach K, Streminska W, Kominek A, Piwocka K, Ciemerych MA, Archacka K. Comparison of Differentiation Pattern and WNT/SHH Signaling in Pluripotent Stem Cells Cultured under Different Conditions. Cells. 2021 Oct 14;10(10):2743. doi: 10.3390/cells10102743. PMID: 34685722; PMCID: PMC8534321.
Minhas R, Loeffler-Wirth H, Siddiqui YH, Obrębski T, Vashisht S, Nahia KA, Paterek A, Brzozowska A, Bugajski L, Piwocka K, Korzh V, Binder H, Winata CL. Transcriptome profile of the sinoatrial ring reveals conserved and novel genetic programs of the zebrafish pacemaker. BMC Genomics. 2021 Oct 2;22(1):715. doi: 10.1186/s12864-021-08016-z. PMID: 34600492; PMCID: PMC8487553.
Maifrede S, Le BV, Nieborowska-Skorska M, Golovine K, Sullivan-Reed K, Dunuwille WMB, Nacson J, Hulse M, Keith K, Madzo J, Caruso LB, Gazze Z, Lian Z, Padella A, Chitrala KN, Bartholdy BA, Matlawska-Wasowska K, Di Marcantonio D, Simonetti G, Greiner G, Sykes SM, Valent P, Paietta EM, Tallman MS, Fernandez HF, Litzow MR, Minden MD, Huang J, Martinelli G, Vassiliou GS, Tempera I, Piwocka K, Johnson N, Challen GA, Skorski T. TET2 and DNMT3A Mutations Exert Divergent Effects on DNA Repair and Sensitivity of Leukemia Cells to PARP Inhibitors. Cancer Res. 2021 Oct 1;81(19):5089-5101. doi: 10.1158/0008-5472.CAN-20-3761. Epub 2021 Jul 2. PMID: 34215619; PMCID: PMC8487956.
Zdżalik-Bielecka D, Poświata A, Kozik K, Jastrzębski K, Schink KO, Brewińska-Olchowik M, Piwocka K, Stenmark H, Miączyńska M. The GAS6-AXL signaling pathway triggers actin remodeling that drives membrane ruffling, macropinocytosis, and cancer-cell invasion. Proc Natl Acad Sci U S A. 2021 Jul 13;118(28):e2024596118. doi: 10.1073/pnas.2024596118. PMID: 34244439; PMCID: PMC8285903.
Libura M, Bialopiotrowicz E, Giebel S, Wierzbowska A, Roboz GJ, Piatkowska-Jakubas B, Pawelczyk M, Gorniak P, Borg K, Wojtas M, Florek I, Matiakowska K, Jazwiec B, Solarska I, Noyszewska-Kania M, Piechna K, Zawada M, Czekalska S, Salamanczuk Z, Karabin K, Wasilewska K, Paluszewska M, Urbanowska E, Gajkowska-Kulik J, Semenczuk G, Rybka J, Wrobel T, Ejduk A, Kata D, Grosicki S, Robak T, Pluta A, Kominek A, Piwocka K, Pyziak K, Sroka-Porada A, Wrobel A, Przybylowicz A, Wojtaszewska M, Lewandowski K, Gil L, Piekarska A, Knopinska W, Bolkun L, Warzocha K, Kuliczkowski K, Sacha T, Basak G, Jedrzejczak WW, Holowiecki J, Juszczynski P, Haus O. IDH2 mutations in patients with normal karyotype AML predict favorable responses to daunorubicin, cytarabine and cladribine regimen. Sci Rep. 2021 May 11;11(1):10017. doi: 10.1038/s41598-021-88120-y. PMID: 33976256; PMCID: PMC8113255.
Swatler J, Turos-Korgul L, Kozlowska E, Piwocka K. Immunosuppressive Cell Subsets and Factors in Myeloid Leukemias. Cancers (Basel). 2021 Mar 10;13(6):1203. doi: 10.3390/cancers13061203. PMID: 33801964; PMCID: PMC7998753
Ochocka N, Segit P, Walentynowicz KA, Wojnicki K, Cyranowski S, Swatler J, Mieczkowski J, Kaminska B. Single-cell RNA sequencing reveals functional heterogeneity of glioma-associated brain macrophages. Nat Commun. 2021 Feb 19;12(1):1151. doi: 10.1038/s41467-021-21407-w. PMID: 33608526
Kolmus K, Erdenebat P, Szymańska E, Stewig B, Goryca K, Derezińska-Wołek E, Szumera-Ciećkiewicz A, Brewińska-Olchowik M, Piwocka K, Prochorec-Sobieszek M, Mikula M, Miączyńska M. Concurrent depletion of Vps37 proteins evokes ESCRT-I destabilization and profound cellular stress responses. J Cell Sci. 2021 Jan 8;134(1):jcs250951. doi: 10.1242/jcs.250951. PMID: 33419951
2020
Polak A, Bialopiotrowicz E, Krzymieniewska B, Wozniak J, Stojak M, Cybulska M, Kaniuga E, Mikula M, Jablonska E, Gorniak P, Noyszewska-Kania M, Szydlowski M, Piechna K, Piwocka K, Bugajski L, Lech-Maranda E, Barankiewicz J, Kolkowska-Lesniak A, Patkowska E, Glodkowska-Mrowka E, Baran N, Juszczynski P. SYK inhibition targets acute myeloid leukemia stem cells by blocking their oxidative metabolism. Cell Death Dis. 2020 Nov 6;11(11):956. doi: 10.1038/s41419-020-03156-8. PMID: 33159047
Le BV, Podszywalow-Bartnicka P, Maifrede S, Sullivan-Reed K, Nieborowska-Skorska M, Golovine K, Yao JC, Nejati R, Cai KQ, Caruso LB, Swatler J, Dabrowski M, Lian Z, Valent P, Paietta EM, Levine RL, Fernandez HF, Tallman MS, Litzow MR, Huang J, Challen GA, Link D, Tempera I, Wasik MA, Piwocka K, Skorski T. TGFβR-SMAD3 Signaling Induces Resistance to PARP Inhibitors in the Bone Marrow Microenvironment. Cell Rep. 2020 Oct 6;33(1):108221. doi: 10.1016/j.celrep.2020.108221. PMID: 33027668
Cendrowski J, Kaczmarek M, Mazur M, Kuzmicz-Kowalska K, Jastrzebski K, Brewinska-Olchowik M, Kominek A, Piwocka K, Miaczynska M. Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells. eLife 2020; 9:e58504. Published online 2020 Aug 14. doi: 10.7554/eLife.58504. PMID: 32795391
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. 2020 Apr;50(4):606-609. doi: 10.1002/eji.201848051. Epub 2019 Dec 5. PubMed PMID: 31758697
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 Feb 7;12(2):e10812. doi: 10.15252/emmm.201910812. Epub 2020 Jan 13. PubMed PMID: 31930723.
2019
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.
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