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Laboratory of Molecular and Cellular Signaling

 


Profile
Leader
Team
Projects
Publications
Contact
Webstie

Profile

Paweł Niewiadomski, PhD, DSc
e-mail: p.niewiadomski@cent.uw.edu.pl
phone: +48 22 55 43693
room: 3.43
ORCID: 0000-0001-6254-6162
SCOPUS ID: 7801593927

Communication between cells is an essential feature of living organisms. Signals received from the environment are processed and integrated by the cell, leading to changes in its morphology and behavior. Many human diseases, such as developmental defects and cancer, are caused by defective signal transduction.

Our laboratory studies various aspects of cellular signaling, with particular focus on the Hedgehog pathway. Hedgehog signaling is involved in the development of limbs, the spinal cord, the heart, and the brain. Its aberrant activation leads to many types of cancer, including the most common childhood brain tumor medulloblastoma. We want to find out how the signal is transmitted from the Hedgehog receptor Patched to Gli transcription factors, which are the main effectors of the pathway in the nucleus. To achieve that goal we use a variety of techniques, including mathematical modeling, genetic manipulation of mammalian cells, fluorescence imaging, qualitative and quantitative proteomics, transcriptomic analyses, mouse models of cancer, and in vivo manipulation of vertebrate embryos. This broad toolbox allows us to approach basic questions in molecular and cell biology from a variety of angles and to shed new light on fundamental mechanisms of signal transduction. We hope that our work will have implications for the treatment of human disease, including cancer.

Leader

Paweł Niewiadomski’s long-term research goal is to understand how signaling pathways regulate transcription of genes in developmental processes and in disease. To this end, his research team is focusing on deciphering the mechanisms that determine transcriptional activity of Gli transcription factors, the main effectors of the Hedgehog signaling pathways. In addition to mechanistic biochemical studies, Paweł’s group also uses “big data” repositories and bioinformatic analyses to find novel promising targets for the treatment of drug-resistant cancers.

Team

Leader
Paweł Niewiadomski, PhD, DSc

PhD Students
Weronika Skarżyńska, MSc
Tomasz Uśpieński, MSc

Selected projects

Title Leader Years Funding
Mechanisms of protein transport to primary cilia P. Niewiadomski 2022-2026 NCN OPUS
The role of epigenetic modifications in Gli3R-dependent Hedgehog pathway repression W. Skarżyńska 2023-2025 NCN PRELUDIUM
Mechanisms of transcriptional repression by Gli proteins in Hedgehog signaling P. Niewiadomski 2020-2023 NCN OPUS
Role of heteromultimerization of MRCK kinases in physiological and pathological processes B. Baran 2020-2023 NCN PRELUDIUM
Role of proteasome in the regulation of Gli protein activity by the Hedgehog pathway P. Niewiadomski 2018-2022 NCN OPUS
Role of the exocyst complex in transport of cytoplasmic proteins to the primary cilium S. Niedziółka 2019-2022 NCN PRELUDIUM
Role of primary cilia in the activation of Gli transcription factors in Hedgehog signaling P. Niewiadomski 2015-2020 NCN SONATA BIS

Selected publications

  • Niedziółka S.M., Datta S., Uśpieński T., Baran B., Skarżyńska W., Humke E.W., Rohatgi R., Niewiadomski P.
    The exocyst complex and intracellular vesicles mediate soluble protein trafficking to the primary cilium
    (2024) Communications Biology, 7 (1), art. no. 213
    DOI: 10.1038/s42003-024-05817-2
  • Baran B., Derua R., Janssens V., Niewiadomski P.
    PP2A phosphatase regulatory subunit PPP2R3C is a new positive regulator of the hedgehog signaling pathway
    (2024) Cellular Signalling, 123, art. no. 111352
    DOI: 10.1016/j.cellsig.2024.111352
  • Uśpieński T., Niewiadomski P.
    The Proteasome and Cul3-Dependent Protein Ubiquitination Is Required for Gli Protein-Mediated Activation of Gene Expression in the Hedgehog Pathway
    (2024) Cells, 13 (17), art. no. 1496
    DOI: 10.3390/cells13171496
  • Baran B., Kosieradzka K., Skarzynska W., Niewiadomski P.
    MRCKα/β positively regulates Gli protein activity
    (2023) Cellular Signalling, 107, art. no. 110666
    DOI: 10.1016/j.cellsig.2023.110666
  • Serifi, I., Besta, S., Karetsou, Z. et al.
    argeting of SET/I2PP2A oncoprotein inhibits Gli1 transcription revealing a new modulator of Hedgehog signaling
    (2021). Sci Rep 11, 13940
    DOI: 10.1038/s41598-021-93440-0
  • Markiewicz, Ł., Uśpieński, T., Baran, B., Niedziółka, S. M., & Niewiadomski, P.
    Xpo7 negatively regulates Hedgehog signaling by exporting Gli2 from the nucleus
    (2021) Cellular Signalling, 109907
    DOI:10.1016/j.cellsig.2020.109907
  • Pęziński, M., Maliszewska-Olejniczak, K., Daszczuk, P., Mazurek, P., Niewiadomski, P., & Rędowicz, M. J.
    Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction.
    (2021).International Journal of Molecular Sciences, 22(21), 12051.
    DOI: 10.3390/ijms222112051
  • Izzo M, Osella S*, Jacquet M, Kiliszek M, Harputlu E, Starkowska A, Łasica A, Unlu CG, Uśpieński T, Niewiadomski P, Bartosik D, Trzaskowski B, Ocakoglu K, Kargul J*
    Enhancement of direct electron transfer in graphene bioelectrodes containing novel cytochrome c553 variants with optimized heme orientation
    (2021) Biolectrochemistry, 140, 107818
    DOI: 10.1016/j.bioelechem.2021.107818
  • Bernadzki, K. M., Daszczuk, P., Rojek, K. O., Pęziński, M., Gawor, M., Pradhan, B. S., … & Niewiadomski, P.
    Arhgef5 Binds α-Dystrobrevin 1 and Regulates Neuromuscular Junction Integrity
    (2020) Frontiers in Molecular Neuroscience, 13, 104
    DOI: 10.3389/fnmol.2020.00104
  • Łastowska, M., Karkucińska-Więckowska, A., Waschek, J., & Niewiadomski, P.
    Differential Expression of Mitochondrial Biogenesis Markers in Mouse and Human SHH-Subtype Medulloblastoma
    (2019) Cells, 8(3), 216
    DOI: 10.3390/cells8030216

Kontakt

Paweł Niewiadomski, PhD, DSc
e-mail: p.niewiadomski@cent.uw.edu.pl
phone: +48 22 55 43693
room: 3.43