Dr Firczuk Team

Małgorzata Firczuk, PhD

Cancer is one of the leading causes of death among children and adults, and current treatments are largely unspecific, associated with severe side effects. There are genetic, metabolic and antigenic differences between tumor cells and normal cells. This can be exploited to develop tailored therapies such as immunotherapy or metabolically-targeted therapy. Our research focuses on better understanding of the differences between cancer and normal cells, crosstalk of cancer with the microenvironment, and mechanisms of cancer immune evasion. We are mainly utilizing models of B cell-derived malignancies.

Research

Targeting tumor-specific metabolic differences

Disturbed oxidative metabolism is a hallmark of solid tumors, but also occurs in hematological malignancies. In B cell acute lymphoblastic leukemia we observed increased oxidative stress accompanied by upregulation of selected enzymes associated with the activity of thioredoxin antioxidant system. Our group investigates how these enzymes cooperate with oncogenic signaling which drive leukemia and how they can be therapeutically targeted for more efficient and less toxic treatments. As our models, we are using ex vivo co-cultures of primary leukemic cells with stromal cells, as well as patient-derived xenograft in vivo models. We extensively collaborate with clinical groups: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Łódź, Department of Laboratory Diagnostics, Medical University of Wasaw, Institute of Hematology and Transfusion Medicine in Warsaw.

 Investigating the mechanism of immune evasion in murine models of leukemia

B cell chronic lymphocytic leukemia (CLL) is the most frequent hematological malignancy in adults. CLL is usually a long-lasting disease but in most patients at some point it takes an aggressive form, resistant to treatment. Also immunotherapies are less effective in CLL than in other malignancies. This may be partially caused by highly immunosuppressive microenvironment observed in CLL. Several immune dysfunctions occur in CLL including exhaustion of T cell, accumulation of regulatory T cells and reprograming of myeloid cell compartments. In our research we try to understand the causes of this immunosuppression. We are using Eµ-TCL1 mice model of CLL, which very well recapitulates immune dysfunctions observed in CLL patients.

Principal investigator

Dr Małgorzata Firczuk graduated from the Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk in 2002 and from Faculty of Pharmacy, Medical University of Gdansk in 2003. She performed her PhD studies in the International Institute of Molecular and Cellular Biology in Warsaw and received her doctoral degree in biological sciences in 2007. In the years 2007-2009 she continued her work as a postdoctoral fellow at the International Institute of Molecular and Cellular Biology. In 2009 she moved to the Department of Immunology, Medical University of Warsaw, where she worked within the TEAM project (2009-2012) and then within BASTION project (2013-2015). Currently, he runs his own research Team at the Immunology Department of the Medical University of Warsaw, where she implements research projects funded by the Polish National Science Center and the Ministry of Science and Higher Education.

Visiting Researcher:

  • June 2017 - July 2017: twinning research visit at the Laboratory of Molecular Hematology in the International Centre of Genetic Engineering and Biotechnology in Trieste, Italy, within the European Commission Horizon 2020 Programme 692180-STREAMH2020-TWINN-2015
  • August 2013: twinning research visit at the Department of Neurological, Neuropsychological, Morphological and Movement Sciences, Medical University of Verona, within the 7PR21/BASTION/WP1

Memberships:

  • Polish Society of Experimental and Clinical Immunology –a member

  • Society for Redox Biology & Medicine –a member

Editorships & Reviewing boards:

  • Chemical Science
  • Cancer research
  • Cancer Immunology, Immunotherapy
  • European Journal of Cancer
  • Oncotarget
  • Cancers
  • International Journal of Molecular Sciences 
  • International Journal of Oncology
  • Oncology letters
  • Molecular Medicine Reports
  • Acta Haematologica Polonica
  • Central European Journal of Immunology
Team members

Senior scientist: Angelika Muchowicz, Phd

Postdoctoral fellows: Agnieszka Góral, PhD

PhD Students: Klaudyna Fidyt, Msc; Łukasz Komorowski, Msc

Msc Students: Julia Cyran

Students: Krzysztof Domka, Marta Śledź

Volunteers: Antoni Domagała

Research projects

1) "Zbadanie mechanizmów oporności na wenetoklaks i sposobów jej zwalczenia w ostrej białaczce limfoblastycznej B komórkowej z rearanżacjami genu MLL”

Preludium, Narodowe Centrum Nauki, Lata realizacji: 2019-2022, Kierownik: mgr inż. Klaudyna Paulina Fidyt 

2)  „Zbadanie roli limfocytów regulatorowych i 2,3-dioksygenazy indoloaminy w progresji i kształtowaniu immunosupresyjnego mikrośrodowiska przewlekłej białaczki limfocytowej”

Opus, Narodowe Centrum Nauki, Lata realizacji: 2019-2021, Kierownik: dr Angelika Muchowicz 

3) „Ocena skuteczności nowych, synergistycznych kombinacji leków w terapii nowotworów wywodzących się z limfocytów B”

Opus, Narodowe Centrum Nauki, Lata realizacji: 2017-2020, Kierownik: dr Małgorzata Firczuk

 4) „Badanie skuteczności nowych pro-oksydacyjnych strategii w leczeniu ostrej białaczki limfoblastycznej B komórkowej”

Sonata bis, Narodowe Centrum Nauki,  Lata realizacji: 2016-2020,  Kierownik: dr Małgorzata Firczuk

Research papers 

2019
Fidyt K, Pastorczak A, Goral A, Szczygiel K, Fendler W, Muchowicz A, Bartlomiejczyk MA, Madzio J, Cyran J, Graczyk-Jarzynka A, Jansen E, Patkowska E, Lech-Maranda E, Pal D, Blair H, Burdzinska A, Pedzisz P, Glodkowska-Mrowka E, Demkow U, Gawle-Krawczyk K, Matysiak M, Winiarska M, Juszczynski P, Mlynarski W, Heidenreich O, Golab J, Firczuk M. Targeting the thioredoxin system as a novel strategy against B-cell acute lymphoblastic leukemia. Mol Oncol. 2019 May;13(5):1180-1195. doi: 10.1002/1878-0261.12476. 

Graczyk-Jarzynka A, Goral A, Muchowicz A, Zagozdzon R, Winiarska M, Bajor M, Trzeciecka A, Fidyt K, Krupka JA, Cyran J, Szczygiel K, Efremov DG, Gobessi S, Jagielski A, Siudakowska K, Bobrowicz M, Klopotowska M, Barankiewicz J, Malenda A, Lech-Maranda E, Miazek-Zapala N, Skarzynski PH, Domagala A, Golab J, Firczuk M. Inhibition of thioredoxin-dependent H(2)O(2) removal sensitizes malignant B-cells to pharmacological ascorbate. Redox Biol. 2019 Feb;21:101062. doi: 10.1016/j.redox.2018.11.020. 

2018                                                                                                                                                        Chlebowska-Tuz J, Sokolowska O, Gaj P, Lazniewski M, Firczuk M, Borowiec K, Sas-Nowosielska H, Bajor M, Malinowska A, Muchowicz A, Ramji K, Stawinski P, Sobczak M, Pilch Z, Rodziewicz-Lurzynska A, Zajac M, Giannopoulos K, Juszczynski P, Basak GW, Plewczynski D, Ploski R, Golab J, Nowis D. Inhibition of protein disulfide isomerase induces differentiation of acute myeloid leukemia cells. Haematologica. 2018 Nov;103(11):1843-1852. doi: 10.3324/haematol.2018.190231.


Bajor M, Zych AO, Graczyk-Jarzynka A, Muchowicz A, Firczuk M, Trzeciak L, Gaj P, Domagala A, Siernicka M, Zagozdzon A, Siedlecki P, Kniotek M, O'Leary PC, Golab J, Zagozdzon R. Targeting peroxiredoxin 1 impairs growth of breast cancer cells and potently sensitises these cells to prooxidant agents. Br J Cancer. 2018 Oct;119(7):873-884. doi: 10.1038/s41416-018-0263-y.


Domagala A, Fidyt K, Bobrowicz M, Stachura J, Szczygiel K, Firczuk M. Typical and Atypical Inducers of Lysosomal Cell Death: A Promising Anticancer Strategy. Int J Mol Sci. 2018 Aug 1;19(8). pii: E2256. doi: 10.3390/ijms19082256. Review.


Domagala A, Stachura J, Gabrysiak M, Muchowicz A, Zagozdzon R, Golab J, Firczuk M. Inhibition of autophagy sensitizes cancer cells to Photofrin-based photodynamic therapy. BMC Cancer. 2018 Feb 20;18(1):210. doi: 10.1186/s12885-018-4126-y. 


2017
Bobrowicz M, Dwojak M, Pyrzynska B, Stachura J, Muchowicz A, Berthel E, Dalla-Venezia N, Kozikowski M, Siernicka M, Miazek N, Zapala P, Domagala A, Bojarczuk K, Malenda A, Barankiewicz J, Graczyk-Jarzynka A, Zagozdzon A, Gabrysiak M, Diaz JJ, Karp M, Lech-Maranda E, Firczuk M, Giannopoulos K, Efremov DG, Laurenti L, Baatout D, Frenzel L, Malinowska A, Slabicki M, Zenz T, Zerrouqi A, Golab J, Winiarska M. HDAC6 inhibition upregulates CD20 levels and increases the efficacy of anti-CD20 monoclonal antibodies. Blood. 2017 Oct 5;130(14):1628-1638. doi: 10.1182/blood-2016-08-736066. 


Winiarska M, Nowis D, Firczuk M, Zagozdzon A, Gabrysiak M, Sadowski R, Barankiewicz J, Dwojak M, Golab J. Selection of an optimal promoter for gene transfer in normal B cells. Mol Med Rep. 2017 Sep;16(3):3041-3048. doi: 10.3892/mmr.2017.6974. 


Graczyk-Jarzynka A, Zagozdzon R, Muchowicz A, Siernicka M, Juszczynski P, Firczuk M. New insights into redox homeostasis as a therapeutic target in B-cell malignancies. Curr Opin Hematol. 2017 Jul;24(4):393-401. doi: 10.1097/MOH.0000000000000351. Review. 


Lechowicz U, Gambin T, Pollak A, Podgorska A, Stawinski P, Franke A, Petersen BS, Firczuk M, Oldak M, Skarzynski H, Ploski R. Iterative Sequencing and Variant Screening (ISVS) as a novel pathogenic mutations search strategy - application for TMPRSS3 mutations screen. Sci Rep. 2017 May 31;7(1):2543. doi: 10.1038/s41598-017-02315-w. 


2016
Gabrysiak M, Wachowska M, Barankiewicz J, Pilch Z, Ratajska A, Skrzypek E, Winiarska M, Domagala A, Rygiel TP, Jozkowicz A, Boon L, Golab J, Firczuk M. Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo. Oncol Rep. 2016 Jun;35(6):3151-8. doi: 10.3892/or.2016.4723.


Trzeciecka A, Klossowski S, Bajor M, Zagozdzon R, Gaj P, Muchowicz A, Malinowska A, Czerwoniec A, Barankiewicz J, Domagala A, Chlebowska J, Prochorec-Sobieszek M, Winiarska M, Ostaszewski R, Gwizdalska I, Golab J, Nowis D, Firczuk M. Dimeric peroxiredoxins are druggable targets in human Burkitt lymphoma. Oncotarget. 2016 Jan 12;7(2):1717-31. doi: 10.18632/oncotarget.6435.


2015
Siernicka M, Winiarska M, Bajor M, Firczuk M, Muchowicz A, Bobrowicz M, Fauriat C, Golab J, Olive D, Zagozdzon R. Adenanthin, a new inhibitor of thiol-dependent antioxidant enzymes, impairs the effector functions of human natural killer cells. Immunology. 2015 Sep;146(1):173-83. doi: 10.1111/imm.12494.


Muchowicz A, Firczuk M, Wachowska M, Kujawa M, Jankowska-Steifer E, Gabrysiak M, Pilch Z, Kłossowski S, Ostaszewski R, Golab J. SK053 triggers tumor cells apoptosis by oxidative stress-mediated endoplasmic reticulum stress. Biochem Pharmacol. 2015 Feb 15;93(4):418-27. doi: 10.1016/j.bcp.2014.12.019.

2014
Muchowicz A, Firczuk M, Chlebowska J, Nowis D, Stachura J, Barankiewicz J, Trzeciecka A, Kłossowski S, Ostaszewski R, Zagożdżon R, Pu JX, Sun HD, Golab J. Adenanthin targets proteins involved in the regulation of disulphide bonds. Biochem Pharmacol. 2014 May 15;89(2):210-6. doi: 10.1016/j.bcp.2014.02.022. 

Nowis D, Malenda A, Furs K, Oleszczak B, Sadowski R, Chlebowska J, Firczuk M, Bujnicki JM, Staruch AD, Zagozdzon R, Glodkowska-Mrowka E, Szablewski L, Golab J. Statins impair glucose uptake in human cells. BMJ Open Diabetes Res Care. 2014 Apr 26;2(1):e000017. doi: 10.1136/bmjdrc-2014-000017.