We study how cells take up and transport various substances within their interior, focusing on how these logistical rules are altered in cancer cells to support their uncontrolled growth. By understanding the differences in cellular functioning between normal and cancerous cells, we aim to guide the development of therapies that selectively target and eliminate cancer cells. We have already identified one such vulnerability, an “Achilles’ heel,” in certain cancer cells and continue our search for additional therapeutic targets.

Research Summary

We are fascinated by two intracellular processes, endocytosis and receptor signaling, and how they are interlinked. We seek to understand how endosomal compartments contribute to the trafficking and signaling of receptors for growth factors and cytokines in normal and cancer cells.
We investigate the roles of endosomal sorting complexes required for transport (ESCRT) in cell physiology and oncogenesis. Our research has revealed that the dysfunction of endosomes caused by the absence of proper ESCRT function induces an intracellular sterile inflammatory reaction.
We also found out that the ESCRT-I complex is indispensable for the biogenesis and proper functioning of lysosomes, as well as energy metabolism in the cell.
The synthetic lethality we identified between two paralogous ATPases of the ESCRT machinery, VPS4A and VPS4B, revealed a novel pair of druggable targets for personalized oncology.
In another line of research, we focus on the receptor tyrosine kinase AXL, which is overexpressed in late-stage cancers. By identifying the interactome of AXL, we revealed that its activation induces several actin-dependent processes, including macropinocytosis.

Scientific Impact

Our studies provide proof of concept that intracellular trafficking and the molecules regulating it can represent a viable therapeutic target in personalized oncology. For example, the synthetic lethality between VPS4A and VPS4B ATPases provides a rationale for developing VPS4 inhibitors for the precision treatment of VPS4B-deficient cancers. Our ongoing studies of AXL-dependent macropinocytosis aim to uncover ways of blocking this process in metastatic and drug-resistant cancers with AXL overexpression.

Future Goals

We wish to understand how altered expression or mutations in the ESCRT components, observed in cancer or some rare diseases, modify cell physiology. In parallel, we aim to elucidate the mechanisms and effector proteins by which the activated AXL receptor drives macropinocytosis in cancer cells.

Collaborations

We collaborate with partners from the IIMCB and external institutions within the HERO consortium project, which aims to develop the next generation of mRNA-based cancer immunotherapies.

Comment

“We study alterations that occur in signaling and trafficking processes in cancer cells because such changes may represent vulnerabilities of cancer cells to specific therapies”, says Prof. Marta Miączyńska


Figure Miaczynska Lab

Human lung adenocarcinoma cells cultured in vitro, with nuclei stained in blue, actin in green, and endosomes in magenta. Image by Patrycja Daszczuk.

mmiaczynska

Marta Miączyńska,  PhD, Professor 

Correspondence address:
Laboratory of Cell Biology
International Institute of Molecular and Cell Biology
4 Ks. Trojdena Street, 02-109 Warsaw, Poland
Email: This email address is being protected from spambots. You need JavaScript enabled to view it. 

DEGREES

2013 - Professor of Biological Sciences, nomination by the President of the Republic of Poland
2008 - DSc Habil in Cell Biology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
1997 - PhD in Genetics, University of Vienna, Austria
1993 - MSc in Molecular Biology, Jagiellonian University, Cracow, Poland
1991 - BSc in Biological Sciences, University of Wolverhampton, UK

 

PROFESSIONAL EMPLOYMENT

2018-present - Director, International Institute of Molecular and Cell Biology in Warsaw, Poland
2014-2015 - Deputy Director for Science, International Institute of Molecular and Cell Biology in Warsaw, Poland
2013-2014 - Deputy Director, International Institute of Molecular and Cell Biology in Warsaw, Poland
2005-present - Professor, Head of Laboratory of Cell Biology, International Institute of Molecular and Cell Biology in Warsaw, Poland

RESEARCH TRAINING

2001-2005 - Senior Postdoctoral Fellow, Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG), Dresden, Germany
1997-2000 - Postdoctoral training, European Molecular Biology Laboratory, Heidelberg, Germany
1993-1996 - PhD studies, Institute of Microbiology and Genetics, University of Vienna, Austria
1990-1991 - Exchange Student, University of Wolverhampton, UK

HONORS, PRIZES AND AWARDS

2024 - Vice Chair of the EMBO Council
2024 - Co-Chair of EU-LIFE Alliance
2021
- Prime Minister's Award for outstanding scientific achievements
2021 - Member, EMBO Council
2020 - Corresponding Member, Polish Academy of Sciences
2019 - Member, Academia Europaea
2017 - Member, European Molecular Biology Organization
2016-2018 - Member, Council of the National Science Centre
2016 - TEAM, Foundation for Polish Science
2012 - MAESTRO, National Science Centre
2011 - Polish-Swiss Research Programme grant
2007 - Habilitation Fellowship of L’Oréal Poland for Women in Science
2006-2012 - International Senior Research Fellowship, Wellcome Trust
2006-2010 - International Research Scholar, Howard Hughes Medical Institute, USA
2006-2010 - Partner Group grant, Max Planck Society, Germany
2001-2004 - Postdoctoral Fellowship, Max Planck Society, Germany
1999-2000 - Long-Term Postdoctoral Fellowship, Human Frontier Science Program Organization
1998-1999 - Erwin Schrödinger Postdoctoral Fellowship, Austrian Science Fund
1993-1996 - Bertha von Suttner PhD Scholarship, Austrian Ministry of Science
1990-1991 - Studentship, European Community Tempus Scheme

DOCTORATES DEFENDED UNDER LAB LEADER’S SUPERVISION

M. Olchowik, A. Urbańska, A. Hupałowska, Ł. Sadowski, A. Mamińska, A. Toruń, K. Jastrzębski, M. Maksymowicz, K. Wojciechowska, A. Poświata, M. Wróbel.

DSC 7105

Lab Leader:
Marta Miączyńska, PhD, Professor

Senior Researcher:
Ewelina Szymańska, PhD

Postdoctoral Researchers:
Patrycja Daszczuk, PhD
Ranjana Maurya, PhD

PhD Students:
Marta Chwałek, MSc
Malwina Grębowicz-Maciukiewicz, MSc
Bartosz Jary, MSc
Zuzanna Miciak, MSc

Research Assistant:
Agnieszka Świstek, MSc

Lab Technician:
Monika Matuszczyk (part-time)

Laboratory Support Specialist:
Renata Wyszyńska, MSc (substitute: Krystyna Gromkowska, PhD)

2025

Ammonia Suppresses the Antitumor Activity of Natural Killer Cells and T Cells by Decreasing Mature Perforin.

Domagala J, Grzywa TM, Baranowska I, Justyniarska M, Tannir R, Graczyk-Jarzynka A, Kusowska A, Lecka M, Poreba M, Fidyt K, Marhelava K, Pilch Z, Picard LK, Wegierski T, Jastrzebski K, Krawczyk M, Klopotowska M, Granica M, Urlaub D, Hajduk S, Neeser A, Moros S, Kozlowski P, Bobrowicz M, Miaczynska M, Ma L, Watzl C, Winiarska M.

Cancer Res. 2025

p70S6 kinase-dependent phosphorylation of the μ2 subunit of the AP2 adaptor complex is needed for clathrin-mediated endocytosis.

Tempes A, Brzozowska A, Węgierski T, Olek K, Jastrzębski K, Liszewska E, Misztal K, Machnicka K, Macias M, Szybińska A, Sitkiewicz E, Gozdz A, Wróbel AG, Miaczynska M, Pokrzywa W, Jaworski J, Malik AR.

bioRxiv. 2025

2024

NFκB and JNK pathways mediate metabolic adaptation upon ESCRT‑I deficiency.

Cendrowski J, Wrobel M, Mazur M, Jary B, Maurya R, Wang S, Korostynski M, Dziewulska A, Rohm M, Kuropka P, Pudelko‑Malik N, Mlynarz P, Dobrzyn A, Zeigerer A, Miaczynska M.

Cell Mol Life Sci. 2024

2023

Ammonia inhibits antitumor activity of NK cells by decreasing mature perforin.

Domagala J, Grzywa TM, Baranowska I, Kusowska A, Fidyt K, Marhelava K, Pilch Z, Graczyk-Jarzynka A, Picard LK, Jastrzebski K, Granica M, Justyniarska M, Urlaub D, Bobrowicz M, Miaczynska M, Watzl C, Winiarska M.

bioRxiv. 2023

Liver sinusoidal endothelial cells constitute a major route for hemoglobin clearance.

Zurawska G, Sas Z, Jończy A, Slusarczyk P, Mahadeva R, Chwałek M, Kulecka M, Rumieńczyk I, Moulin M, Jastrzębski K, Mikula M, Etzerodt A, Miączyńska M, Rygiel TP, Mleczko-Sanecka K.

bioRxiv. 2023

2022

ESCRT-I fuels lysosomal degradation to restrict TFEB/TFE3 signaling via the Rag-mTORC1 pathway

Wróbel M, Cendrowski J, Szymańska E, Grębowicz-Maciukiewicz M, Budick-Harmelin N, Macias M, Szybińska A, Mazur M, Kolmus K, Goryca K, Dąbrowska M, Paziewska A, Mikula M, Miączyńska M.

Life Sci Alliance. 2022

Vps37a regulates hepatic glucose production by controlling glucagon receptor localization to endosomes.

Sekar R, Motzler K, Kwon Y, Novikoff A, Jülg J, Najafi B, Wang S, Warnke AL, Seitz S, Hass D, Gancheva S, Kahl S, Yang B, Finan B, Schwarz K, Okun JG, Roden M, Blüher M, Müller TD, Krahmer N, Behrends C, Plettenburg O, Miaczynska M, Herzig S, Zeigerer A.

Cell Metab. 2022

The molecular network of the proteasome machinery inhibition response is orchestrated by HSP70, revealing vulnerabilities in cancer cells.

Oroń M, Grochowski M, Jaiswar A, Legierska J, Jastrzębski K, Nowak-Niezgoda M, Kołos M, Kaźmierczak W, Olesiński T, Lenarcik M, Cybulska M, Mikula M, Żylicz A, Miączyńska M, Zettl K, Wiśniewski JR, Walerych D.

Cell Rep. 2022

Tollip-deficient zebrafish display no abnormalities in development, organ morphology or gene expression in response to lipopolysaccharide.

Wolińska-Nizioł L, Romaniuk K, Wojciechowska K, Surga K, Kamaszewski M, Szudrowicz H, Miączyńska M.

FEBS Open Bio. 2022

Endocytic trafficking of GAS6-AXL complexes is associated with sustained AKT activation.

Poświata A, Kozik K, Miączyńska M, Zdżalik-Bielecka D.

Cell Mol Life Sci. 2022

Bemcentinib and gilteritinib inhibit cell growth and impair the endo-lysosomal and autophagy systems in an AXL-independent manner.

Zdzalik-Bielecka D, Kozik K, Poswiata A, Jastrzebski K, Jakubik M, Miaczynska M.

Mol Cancer Res. . 2022

2021

Dissecting biological activities of fibroblast growth factor receptors by the coiled-coil-mediated oligomerization of FGF1.

Porebska N, Pozniaka M, Krzyscik MA, Knapika A, Czyrek A, Kucinska M, Jastrzebski K, Zakrzewska M, Otlewski J, Opalinski L.

Int J Biol Macromol.. 2021

Concurrent depletion of Vps37 proteins evokes ESCRT-I destabilization and profound cellular stress responses.

Kolmus K, Erdenebat P, Szymańska E, Stewig B, Goryca K, Derezinska-Wolek E, Szumera-Cieckiewicz A, Brewinska-Olchowik M, Piwocka K, Prochorec-Sobieszek M, Mikula M, Miaczynska M.

J Cell Sci.. 2021

The GAS6-AXL signaling pathway triggers actin remodeling that drives membrane ruffling, macropinocytosis, and cancer-cell invasion.

Zdżalik-Bielecka D, Poświata A, Kozik K, Jastrzębski K, Schink KO, Brewińska-Olchowik M, Piwocka K, Stenmark H, Miączyńska M.

Proc Natl Acad Sci USA. 2021

Modular self-assembly system for development of oligomeric, highly internalizing and potent cytotoxic conjugates targeting fibroblast growth factor receptors.

Poźniak M, Porębska N, Jastrzębski K, Krzyścik MA, Kucińska M, Zarzycka W, Barbach A, Zakrzewska M, Otlewski J, Miączyńska M, Opaliński Ł.

J Biomed Sci.. 2021

2020

Clathrin- and dynamin-dependent endocytosis limits canonical NF-κB signaling triggered by lymphotoxin β receptor.

Maksymowicz M, Miączyńska M, Banach-Orłowska M.

Cell Commun Signal.. 2020

Splicing variants of an endocytic regulator, BMP2K, differentially control autophagic degradation in erythroid cells.

Cendrowski J, Miaczynska M.

Autophagy. 2020

Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells.

Cendrowski J, Kaczmarek M, Mazur M, Kuzmicz-Kowalska K, Jastrzebski K, Brewinska-Olchowik M, Kominek A, Piwocka K, Miaczynska M.

eLife . 2020

FGFR1 Clustering With Engineered Tetravalent Antibody Improves the Efficiency and Modifies the Mechanism of Receptor Internalization.

Pozniak M, Sokolowska-Wedzina A, Jastrzebski K, Szymczyk J, Porebska N, Krzyscik MA, Zakrzewska M, Miaczynska M, Otlewski J, Opalinski L.

Mol Oncol. . 2020

Membrane Trafficking: Vesicle Formation, Cargo Sorting and Fusion.

 Miaczynska M, Munson M.

Mol Biol Cell. . 2020

Synthetic lethality between VPS4A and VPS4B triggers an inflammatory response in colorectal cancer.

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.

EMBO Mol Med.. 2020

2019

Cholesterol restricts lymphotoxin β receptor-triggered NF-κB signaling.

Banach-Orłowska M, Wyszyńska R, Pyrzyńska B, Maksymowicz M, Gołąb J, Miączyńska M.

Cell Commun Signal.. 2019

2018

Integration of the Endocytic System into the Network of Cellular Functions.

Budick-Harmelin N, Miaczynska M.

Prog Mol Subcell Biol.. 2018

The topology of lymphotoxin β receptor accumulated upon endolysosomal dysfunction dictates the NF-κB signaling outcome.

Banach-Orłowska M, Jastrzębski K, Cendrowski JMaksymowicz M, Wojciechowska K, Korostyński M, Moreau D, Gruenberg J, Miaczynska M.

J Cell Sci.. 2018

2017

Endosomal "sort" of signaling control: The role of ESCRT machinery in regulation of receptor-mediated signaling pathways.

Szymanska E, Budick-Harmelin N, Miaczynska M.

Semin Cell Dev Biol.. 2017

Multiple routes of endocytic internalization of PDGFRβ contribute to PDGF-induced STAT3 signaling

Jastrzębski K, Zdżalik-Bielecka D, Mamińska A, Kalaidzidis Y, Hellberg C, Miaczynska M

J Cell Sci.. 2017

2016

Genome-wide co-localization of active EGFR and downstream ERK pathway kinases mirrors mitogen-inducible RNA polymerase 2 genomic occupancy.

Mikula M, Skrzypczak M, Goryca K, Paczkowska K, Ledwon JK, Statkiewicz M, Kulecka M, Grzelak M, Dabrowska M, Kuklinska U, Karczmarski J, Rumienczyk I, Jastrzebski K, Miaczynska M, Ginalski K, Bomsztyk K, Ostrowski J.

Nucleic Acids Res. 2016

Lipid peroxidation in face of DNA damage, DNA repair and other cellular processes

Tudek B, Zdżalik-Bielecka D, Tudek A, Kosicki K, Fabisiewicz A, Speina E

Free Radic Biol Med. 2016

Endocytic regulation of cytokine receptor signaling

Cendrowski J, Mamińska A, Miaczynska M

Cytokine Growth Factor Rev. 2016

APPL proteins promote TGFβ-induced nuclear transport of the TGFβ type I receptor intracellular domain

Song J, Mu Y, Li C, Bergh A, Miaczynska M, Heldin CH, Landström M

Oncotarget. 2016

ESCRT proteins restrict constitutive NF-κB signaling by trafficking cytokine receptors

Mamińska A, Bartosik A, Banach-Orłowska M, Pilecka I, Jastrzębski K, Zdżalik-Bielecka D, Castanon I, Poulain M, Neyen C, Wolińska-Nizioł L, Toruń A, Szymańska E, Kowalczyk A, Piwocka K, Simonsen A, Stenmark H, Fürthauer M, González-Gaitán M, Miaczynska M

Sci Signal. 2016

Impaired dynamin 2 function leads to increased AP-1 transcriptional activity through the JNK/c-Jun pathway

Szymanska E, Skowronek A, Miaczynska M

Cell Signal. 2016

2015

APPL endosomes are not obligatory endocytic intermediates but act as stable cargo-sorting compartments

Kalaidzidis I, Miaczynska M, Brewińska-Olchowik M, Hupalowska A, Ferguson C, Parton RG, Kalaidzidis Y, Zerial M

J Cell Biol. 2015

APPL1 endocytic adaptor as a fine tuner of Dvl2-induced transcription

Banach-Orlowska M, Szymanska E, Miaczynska M

FEBS Lett. 2015

Endocytic adaptor protein Tollip inhibits canonical Wnt signaling

Torun A, Szymańska E, Castanon I, Wolińska-Nizioł L, Bartosik A, Jastrzębski K, Miętkowska M, González-Gaitán M, Miaczynska M

PLoS One. 2015

Missense variant in CCDC22 causes X-linked recessive intellectual disability with features of Ritscher-Schinzel/3C syndrome

Kolanczyk M, Krawitz P, Hecht J, Hupalowska A, Miaczynska M, Marschner K, Schlack C, Emerich D, Kobus K, Kornak U, Robinson PN, Plecko B, Grangl G, Uhrig S, Mundlos S, Horn D

Eur J Hum Genet. 2015

2014

Labeling of platelet-derived growth factor by reversible biotinylation to visualize its endocytosis by microscopy

Sadowski Ł, Jastrzębski K, Purta E, Hellberg C, Miaczynska M

Methods Enzymol.. 2014

2013

Effects of membrane trafficking on signaling by receptor tyrosine kinases

Miaczynska M

Cold Spring Harb Perspect Biol.. 2013

Dynamin Inhibitors Impair Endocytosis and Mitogenic Signaling of PDGF

Sadowski L, Jastrzębski K, Kalaidzidis Y, Heldin CH, Hellberg C, Miaczynska M

Traffic. 2013

Multifunctional protein APPL2 contributes to survival of human glioma cells

Pyrzynska B, Banach-Orlowska M, Teperek-Tkacz M, Miekus K, Drabik G, Majka M, Miaczynska M

Mol Oncol.. 2013

2012

P14ARF inhibits human glioblastoma-induced angiogenesis by upregulating the expression of TIMP3

Zerrouqi A, Pyrzynska B, Febbraio M, Brat DJ, Van Meir EG

J Clin Invest.. 2012

The new faces of endocytosis in signaling

Hupalowska A, Miaczynska M

Traffic. 2012

APPL1 regulates basal NF-κB activity by stabilizing NIK

Hupalowska A, Pyrzynska B, Miaczynska M

J Cell Sci. 2012

Prenyltransferases Regulate CD20 Protein Levels and Influence Anti-CD20 Monoclonal Antibody-mediated Activation of Complement-dependent Cytotoxicity

Winiarska M, Nowis D, Bil J, Glodkowska-Mrowka E, Muchowicz A, Wanczyk M, Bojarczuk K, Dwojak M, Firczuk M, Wilczek E, Wachowska M, Roszczenko K, Miaczynska M, Chlebowska J, Basak GW, Golab J

J Biol Chem. 2012

2011

Biochemical characterization of APPL endosomes: the role of annexin A2 in APPL membrane recruitment

Urbanska A, Sadowski L, Kalaidzidis Y, Miaczynska M

Traffic. 2011

Recruitment of APPL1 to ubiquitin-rich aggresomes in response to proteasomal impairment

Pilecka I, Sadowski L, Kalaidzidis Y, Miaczynska M

Exp Cell Res. 2011

2010

Signaling endosomes: seeing is believing

Miaczynska M, Bar-Sagi D

Curr Opin Cell Biol. 2010

2009

Reconstitution of Rab- and SNARE-dependent membrane fusion by synthetic endosomes.

Ohya T, Miaczynska M, Coskun U, Lommer B, Runge A, Drechsel D, Kalaidzidis Y, Zerial M

Nature. 2009

[Effectors of GTPase Rab5 in endocytosis and signal transduction]

Olchowik M, Miaczyńska M

Postepy Biochem. 2009

Functional characterization of the interactions between endosomal adaptor protein APPL1 and the NuRD co-repressor complex

Banach-Orlowska M, Pilecka I, Torun A, Pyrzynska B, Miaczynska M

Biochem J. 2009

Signaling from endosomes: location makes a difference.

Sadowski L, Pilecka I, Miaczynska M

Exp Cell Res. 2009

Endosomal adaptor proteins APPL1 and APPL2 are novel activators of beta-catenin/TCF-mediated transcription.

Rashid S, Pilecka I, Torun A, Olchowik M, Bielinska B, Miaczynska M

J Biol Chem. 2009

Endocytic proteins in the regulation of nuclear signaling, transcription and tumorigenesis

Pyrzynska B, Pilecka I, Miaczynska M

Mol Oncol. 2009

2008

On the transition from the meiotic to mitotic cell cycle during early mouse development.

Kubiak JZ, Ciemerych MA, Hupalowska A, Sikora-Polaczek M, Polanski Z

Int J Dev Biol. 2008

Mechanisms and functions of endocytosis.

Miaczynska M, Stenmark H

J Cell Biol. 2008

2007

Nuclear functions of endocytic proteins

Pilecka I, Banach-Orlowska M, Miaczynska M

Eur J Cell Biol. 2007