RESEARCH INTERESTS

The Laboratory of Molecular OncoSignalling is interested in cancer biology, cellular signalling during oncogenesis and the identification of novel targets for cancer therapies.

Signal transduction plays an important role in cancer development and protein kinases, which are the master regulators of signalling pathways, represent key targets in cancer treatment. Our group wants to understand how aberrant signalling in cancer cells contributes to cancer development, metastasis or therapy resistance, and how we can use that knowledge to design novel anticancer treatments.  

 

In particular, we focus on investigating oncogenic signalling activated by MLK4 in breast cancer. MLK4 is a member of Mixed-Lineage Kinase family of serine/threonine kinases that are activated by environmental stress, cytokines and growth factors and play a role in a variety of cellular processes. The members of MLK family have been involved in the regulation of a wide range of disorders including cancer, inflammation, metabolic and neurobiological disorders. Our lab investigates MLK4 signalling in breast cancer, where MLK4 is highly upregulated and contributes to malignant progression. One of our projects is focused on understanding the role of MLK4 in the response to chemotherapy in breast cancer. Furthermore, we aim to develop and validate the potency and efficacy of first-in-class MLK4-targeting compounds. We are also interested in uncovering the importance of MLK4-dependent cross-talk signalling between components of tumour microenvironment and breast cancer cells.

 

In our studies we use human and mouse cancer cell lines and syngeneic as well as xenograft tumour models in mice. We also use 3D cell cultures, flow cytometry, mass spectrometry and various phenotypic assays including invasion and migration assays.

 

MEMBERS OF THE GROUP

Country
Name
Surname
Science Degree
Email
Agnieszka
Borowiec
a.borowiec@imol.institute
Dagmara
Dymerska
PhD
d.dymerska@imol.institute
Anna
Marusiak
PhD
a.marusiak@imol.institute
Alicja
Mazan
a.mazan@imol.institute
Dawid
Mehlich
d.mehlich@imol.institute
Marina
Papadimitriou
m.papadimitriou@imol.institute
Michał
Łomiak
m.lomiak@imol.institute
 

PUBLICATIONS

2021

  • MLK4 regulates DNA damage response and promotes triple-negative breast cancer chemoresistance. Dawid Mehlich, Michał Łomiak, Aleksandra Sobiborowicz, Alicja Mazan, Dagmara Dymerska,  Łukasz Szewczyk, Anna Mehlich, Agnieszka Borowiec, Monika Prełowska, Adam Gorczyński, Paweł Jabłoński, Ewa Iżycka-Świeszewska, Dominika Nowis, Anna Marusiak*. Cell Death and Disease, 2021

  • Inhibition of the ʟ-glutamine transporter ASCT2 sensitizes plasma cell myeloma cells to proteasome inhibitors Monika K. Prelowska, Dawid Mehlich, M. Talha Ugurlu, Hanna Kedzierska, Aleksandra Cwiek, Artur Kosnik, Klaudia Kaminska, Anna A. Marusiak, Dominika Nowis, Cancer Letters, 2021

2020

  • Differential responses to kinase inhibition in FGFR2-addicted triple negative breast cancer cells: a quantitative phosphoproteomics study. Debbie L. Cunningham, Adil R. Sarhan, Andrew Creese, Katherine Larkins, Hongyan Zhao, Harriet Ferguson, Katie Baker, Anna A. Marusiak, Helen J. Cooper, John K. Heath. Scientific Reports, 2020

2019

  • Upregulation of MLK4 promotes migratory and invasive potential of breast cancer cells. Anna A. Marusiak*, Monika K. Prelowska, Dawid Mehlich, Michal Lazniewski, Klaudia Kaminska, Adam Gorczynski, Aleksandra Korwat, Olga Sokolowska, Hanna Kedzierska, Jakub Golab, Wojciech Biernat, Dariusz Plewczynski, John Brognard, Dominika Nowis. Oncogene, 2019

2016

  • Somatically mutated ABL1 is an actionable and essential NSCLC survival gene. Ewelina Testoni, Natalie L. Stephenson, Pedro Torres-Ayuso, Anna A. Marusiak, Eleanor W. Trotter, Andrew Hudson, Cassandra L. Hodgkinson, Christopher J. Morrow, Caroline Dive, John Brognard. EMBO Molecular Medicine, 2016

  • Recurrent MLK4 loss-of-function mutations suppress JNK signalling to promote colon tumorigenesis. Anna A. Marusiak, Natalie L. Stephenson, Hayeon Baik, Eleanor W. Trotter, Yayong Li, Karen Blyth, Susan Mason, Phil Chapman, Lorena A. Puto, Jon A. Read, Claire Brassington, Helen K. Pollard, Chris Phillips, Isabelle Green, Ross Overman, Matthew Collier, Ewelina Testoni, Crispin J. Miller, Tony Hunter, Owen J. Sansom, John Brognard. Cancer Research, 2016

 

2015

  • Paradox-breaking BRAF inhibitors are effective in melanomas that are resistant to BRAF-selective or BRAF plus MEK inhibitor combinations. Maria R. Girotti, Filipa Lopes, Natasha Preece, Dan Niculescu-Duvaz, Alsonso Zambon, Lawrence Davies, Steven Whittaker, Grazia Saturno, Amaya Viros, Malin Pedersen, Bart M.J.M. Suijkerbuijk, Delphine Menard, Robert McLeary, Louise Johnson, Laura Fish, Sarah Ejiama, Berta Sanchez-Laorden, Neil Oliver Carragher, Kenneth MacLeod, Garry Ashton, Anna A. Marusiak, Alberto Fusi, John Brognard, Margaret Frame, Paul Lorigan, Caroline Springer, Richard Marais. Cancer Cell, 2015

2014

  • Mixed lineage kinases activate MEK independently of RAF to mediate resistance to RAF inhibitors. Anna A. Marusiak, Zoe C. Edwards, Willy Hugo, Eleanor W. Trotter, Maria R. Girotti, Natalie L. Stephenson, Xiangju Kong, Michael G. Gartside, Shameem Fawdar, Andrew Hudson, Wolfgang Breitwieser, Nicholas K. Hayward, Richard Marais, Roger S. Lo, John Brognard. Nature Communications, 2014

 

2013

  • Targeted genetic dependency screen facilitates identification of actionable mutations in FGFR4, MAP3K9, and PAK5 in lung cancer.  Shameem Fawdar, Eleanor W. Trotter, Yaoyong Li, Natalie L. Stephenson, Franziska Hanke, Anna A. Marusiak, Zoe C. Edwards, Sara Ientile, Bohdan Waszkowycz, Crispin J. Miller, John Brognard. PNAS, 2013

  • Protein kinase C δ deficiency causes mendelian systemic lupus erythematosus with B-cell defective apoptosis and hyperproliferation.  Belot A, Kasher PR, Trotter EW, Foray AP, Debaud AL, Rice GI, Szynkiewicz M, Zabot MT, Rouvet I, Bhaskar SS, Daly SB, Dickerson JE, Mayer J, O'Sullivan J, Juillard L, Urquhart JE, Fawdar S, Anna A. Marusiak, Stephenson N, Waszkowycz B, Beresford MW, Biesecker LG, Black GM, René C, Eliaou JF, Fabien N, Ranchin B, Cochat P, Gaffney PM, Rozenberg F, Lebon P, Malcus C, Crow YJ, Brognard J, Bonnefoy N. Arthritis Rheum., 2013

 

2010

  • Signal transducers and activators of transcription-3 binding to the fibroblast growth factor receptor is activated by receptor amplification. Anna A. Dudka, Steve M. Sweet, John K. Heath Cancer Research, 2010

 

2009

  • Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway. Maria L. Guerriero, Anna A. Dudka, Nicholas Underhill-Day, John K. Heath, C. Priami BMC Syst Biology, 2009

* corresponding author

 

ABOUT GROUP LEADER

SHORT BIO

Anna Marusiak is a head of The Laboratory of OncoSignalling. After graduating from the University of Wrocław in medical biotechnology, she completed the PhD course in CRUK Growth Factor Group at the University of Birmingham under the supervision of Prof. John Heath. During 2011-2015 she was a postdoctoral fellow at the Cancer Research UK Manchester Institute in Signalling Networks in Cancer Group led by Dr John Brognard. In 2015 she joined Prof. Dominika Nowis’s (Laboratory of Experimental Medicine) at the Centre of New Technologies, University of Warsaw. She was a project leader of three grants (Fuga, Homing, Sonata). In August 2021, she became a group leader at IMol PAS.

 

FUNDING

Anna Marusiak’s grant

 

2022-2027

SONATA BIS (National Science Centre), amount: 4 035 160 PLN, principal investigator.

2020 - 2021

Excellence Initiative (IDUB) programme, project entitled: ”The combination of MLK4 inhibition and chemotherapy in animal studies” amount 50 600 PLN, principal investigator (gratefully declined).

 

2019 – 2022

SONATA (National Science Centre), project entitled: “The importance of MLK4 signalling in the communication between breast cancer cells and tumour-associated macrophages”, amount 1 303 398 PLN, principal investigator.

2017 – 2019

HOMING (Foundation for Polish Science), project entitled “The role of MLK4 amplification in breast cancer progression - studies in 3D cell culture and in vivo models", amount 799 760 PLN, principal investigator.

 

2018

Travel Grant from Biochemical Society.

2017

Travel Grant from Cell Signaling Technologies.

 

2016 - 2019

Fellowship for Outstanding Young Researchers from the Ministry of Science and Higher Education.

2015 – 2018

FUGA (National Science Centre), project entitled “The effect of increased MLK4 expression on breast cancer progression”, amount 612 000 PLN, principal investigator.

 

2005 – 2006

Socrates/Erasmus studentship, University of Reims, France

Lab members' grants

 

2022-2024

PRELUDIUM (National Science Centre), principal investigator, Dawid Mehlich.

 

2022

Fulbright Junior Research Award, Dawid Mehlich

 

2021

Scholarship from the Polish National Agency of Academic Exchange, Dawid Mehlich

 

LAB’S LIFE

 
 

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