Dr Firczuk Team
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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. |
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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:
Memberships:
Editorships & Reviewing boards:
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| 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 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.
2014 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. |
