Research group - Beata Pyrzynska, PhD


 

 Research interest

 

  • Development of new cancer therapeutic alternatives for combination with antibody-based immunotherapies
  • Tumor microenvironmental factors modulating anti-cancer immune response and immunotherapies
  • Molecular mechanisms regulating endocytic and exocytic pathways

Broadly speaking the research interest of Dr Beata Pyrzynska focuses on elucidating the mechanisms of tumorignesis and the development of new cancer therapeutic strategies. Using her experience in molecular and cell biology, cancer modeling in mice and tumor immunology, she is studying the regulation of cellular signaling pathways shaping gene expression profiles and tumor resistance to immunotherapies in solid and hematological malignancies.

Malignant B cells (such as lymphoma cells) are able to escape from therapy by the downregulation of surface molecules, which are used as targets for therapeutic monoclonal antibodies. The same surface molecules are also important components of the Extracellular Vesicles (EVs), released by cancer cells. By competing with cancer cells for therapeutic monoclonal antibodies, the cancer-derived EVs are able to impair the efficacy of therapeutic antibodies. Therefore the ultimate goal of Dr. Pyrzynska’s research is to provide molecular basis for designing improved lymphoma-directed therapies, combining monoclonal antibodies with drugs that are able to decrease the abundance of targeted molecules on cancer-derived EVs with simultaneous increase in number of these molecules on the surface of cancer cells.

Beside the cancer-derived EVs, the cancer-derived metabolites render the tumor microenvironment strongly immunosuppressive. The immunotherapeutic approaches are currently revolutionizing field of oncology. Patient's immune cells are used to produce the genetically modified T lymphocytes and NK cells (e.g. CAR-T or CAR-NK cells), able to attack tumors efficiently. However, highly concentrated tumor cell metabolites are able to inhibit innate and adaptive immunity as well as impair the efficacy of antibody- and cell-based immunotherapies, such as checkpoint inhibitors, CAR-T or CAR-NK cells. We are actively searching for new ways to restore cytotoxic activity of NK and T cells dampened by the tumor microenvironment. The basic findings will be further used for designing of curative therapies for cancer patients.

Biography

Beata Pyrzynska graduated with Ph.D degree from the Nencki Institute of Experimental Biology in Warsaw, Poland. She continued her education during postdoctoral trainings in the Winship Cancer Institute, Emory University (Atlanta, GA, USA) and the International Institute of Molecular and Cell Biology (IIMCB) in Warsaw. In 2013, she was recruited as an experienced scientist for implementation of BASTION project (international collaboration in the field of oncology, supported by the European Commission under FP7); http://bastion.wum.edu.pl/en/zespol-projektu-bastion/beata-pyrzynska/. The project was coordinated by the Medical University of Warsaw (MUW). In the years 2016-2018, Dr. Pyrzynska served as work package leader for the implementation of STREAM project in the Dept. of Immunology at MUW (EC-funded grant, based on European collaboration in the field of immuno-oncology; under Horizon2020 program (http://www.stream.wum.edu.pl/en/about-the-project/project-coordinator).

During her scientific career Dr. Pyrzynska has been a visiting researcher in the following institutions:

  • Oct.-Nov. 2018: The Francis Crick Institute, London, United Kingdom; collaboration with Prof. Dinis Calado
  • June-July 2018: International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy; collaboration with Prof. Dimitar Efremov
  • Feb.-March and Oct.-Nov. 2017: International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy; collaboration with Prof. Dimitar Efremov
  • August-Sept. 2016: The Francis Crick Institute, London, United Kingdom; collaboration with Prof. Dinis Calado
  • June-July 2015: Inserm, U1068, Centre Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, CNRS, UMR7258, Aix-Marseille University, Marseille, France; collaboration with Dr. Cyril Fauriat
  • 2002-2006: Postdoctoral training; Winship Cancer Institute, Emory University, Atlanta, GA, USA; PI: Prof. Erwin G. Van Meir
  • Feb.-July 1999 and Oct. 2000: EMBO Fellowship, National Center of Biotechnology, Dept. of Immunology and Oncology, Madrid, Spain; Collaboration with Dr. Manuel Serrano and Prof. Carlos Martinez-A.

Recently Dr. Pyrzynska and her research group moved to the Dept. of Biochemistry at MUW, where she is co-leading the EVIONA project. The collaborative research visits are planned to four Partner Institutions (in USA and Europe).

Research team members

  • Abdessamad Zerrouqi, PhD Scientific advisor
  • Marta Wlodarczyk, PhD, Postdoctoral fellow
  • Aleksandra Zdanowicz, PhD student

  • Anna Torun, MD PhD, former member
  • Nina Miazek-Zapala, MD, former member

Ongoing projects

  • Testing of cation carrier derivatives as prospective therapeutic agents for the treatment of B-cell-derived malignancies. PI: Pyrzynska B.; National Science Centre (NCN, Poland); OPUS; duration: 2020-2024
  • NK cells with inducible expression of CAR as novel immunotherapy increasing the efficacy of monoclonal antibodies. PI: Pyrzynska B.; National Science Centre (NCN, Poland); OPUS; duration: 2017-2022

Finished projects

  • Strategy to overcome immunosuppression in immunotherapy of cancer. PI: Zerrouqi A.; Ministry of Science and Higher Education (MNiSW, Poland); Innovation Incubator 2.0; duration: 2019-2020
  • Effects of selected chemotherapeutics on the efficacy of anti-CD20 immunotherapy in B cell-derived malignancies. PI: Miazek N.; Supervisor: Pyrzynska B.; Ministry of Science and Higher Education (MNiSW, Poland); Diamond Grant; duration: 2016-2019
  •  Influence of AKT signaling pathway on CD20 expression and antitumor activity of therapeutic monoclonal antibodies. PI: Pyrzynska B.; National Science Centre (NCN, Poland); OPUS; duration: 2014-2017
  •  Role of multifunctional adapter proteins APPL1 and APPL2 in the regulation of cell growth and tumor properties. PI: Pyrzynska B.; Ministry of Science and Higher Education (MNiSW, Poland); research project; duration: 2010-2013

 

Recent publications

Szydlowski M, Garbicz F, Jablonska E, Gorniak P, Komar D, Pyrzynska B, Bojarczuk K, Prochorec-Sobieszek M, Szumera-Cieckiewicz A, Rymkiewicz G, et al.: Inhibition of PIM  kinases in DLBCL targets MYC transcriptional program and augments the efficacy of anti-CD20 antibodies. Cancer Res. 2021, 81:6029-6043.

Torun A, Hupalowska A, Trzonkowski P, Kierkus J and Pyrzynska B: Intestinal microbiota in common chronic inflammatory disorders affecting children. Front Immunol. 2021, 12:642166.

Lee SH, Khwaja Rehman F, Tyler KC, Yu B, Zhang Z, Osuka S, Zerrouqi A, Kaluzova M, Hadjipanayis CG, Cummings RD, et al.: A Chimeric Signal Peptide-Galectin-3 Conjugate Induces Glycosylation-Dependent Cancer Cell-Specific Apoptosis. Clin Cancer Res 2020.

Sasi BK, Martines C, Xerxa E, Porro F, Kalkan H, Fazio R, Turkalj S, Bojnik E, Pyrzynska B, Stachura J, et al.: Inhibition of SYK or BTK augments venetoclax sensitivity in SHP1-negative/BCL-2-positive diffuse large B-cell lymphoma. Leukemia 2019, 33:2416-2428.

Banach-Orlowska M, Wyszynska R, Pyrzynska B, Maksymowicz M, Golab J, Miaczynska M: Cholesterol restricts lymphotoxin beta receptor-triggered NF-kappaB signaling. Cell Commun Signal 2019, 17:171.

Pyrzynska B, Dwojak M, Zerrouqi A, Morlino G, Zapala P, Miazek N, Zagozdzon A, Bojarczuk K, Bobrowicz M, Siernicka M, et al.: FOXO1 promotes resistance of non-Hodgkin lymphomas to anti-CD20-based therapy. Oncoimmunology 2018, 7:e1423183.

Bobrowicz M, Dwojak M, Pyrzynska B, Stachura J, Muchowicz A, Berthel E, Dalla-Venezia N, Kozikowski M, Siernicka M, Miazek N, et al.: HDAC6 inhibition upregulates CD20 levels and increases the efficacy of anti-CD20 monoclonal antibodies. Blood 2017, 130:1628-1638.

Slabicki M, Lee KS, Jethwa A, Sellner L, Sacco F, Walther T, Hullein J, Dietrich S, Wu B, Lipka DB, et al.: Dissection of CD20 regulation in lymphoma using RNAi. Leukemia 2016, 30:2409-2412.

Dwojak M, Bobrowicz M, Bil J, Bojarczuk K, Pyrzynska B, Siernicka M, Malenda A, Lech-Maranda E, Tomczak W, Giannopoulos K, et al.: Sorafenib improves rituximab and ofatumumab efficacy by decreasing the expression of complement regulatory proteins. Blood Cancer J 2015, 5:e300.

Zerrouqi A, Pyrzynska B, Brat DJ, Van Meir EG: P14ARF suppresses tumor-induced thrombosis by regulating the tissue factor pathway. Cancer Res 2014, 74:1371-1378.

Winiarska M, Bojarczuk K, Pyrzynska B, Bil J, Siernicka M, Dwojak M, Bobrowicz M, Miazek N, Zapala P, Zagozdzon A, et al.: Inhibitors of SRC kinases impair antitumor activity of anti-CD20 monoclonal antibodies. MAbs 2014, 6:1300-1313.

Bojarczuk K, Siernicka M, Dwojak M, Bobrowicz M, Pyrzynska B, Gaj P, Karp M, Giannopoulos K, Efremov DG, Fauriat C, et al.: B-cell receptor pathway inhibitors affect CD20 levels and impair antitumor activity of anti-CD20 monoclonal antibodies. Leukemia 2014, 28:1163-1167.

Pyrzynska B, Banach-Orlowska M, Teperek-Tkacz M, Miekus K, Drabik G, Majka M, Miaczynska M: Multifunctional protein APPL2 contributes to survival of human glioma cells. Mol Oncol 2013, 7:67-84.

Zerrouqi A, Pyrzynska B, Febbraio M, Brat DJ, Van Meir EG: P14ARF inhibits human glioblastoma-induced angiogenesis by upregulating the expression of TIMP3. J Clin Invest 2012, 122:1283-1295.

Hupalowska A, Pyrzynska B, Miaczynska M: APPL1 regulates basal NF-kappaB activity by stabilizing NIK. J Cell Sci 2012, 125:4090-4102.