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Laboratory of the Molecular Biology of Cancer

 


Profile
Leader
Team
Projects
Publications
Contact
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Profile

Prof. Agnieszka Kobielak
e-mail: a.kobielak@cent.uw.edu.pl
phone: +48 22 55 43735
room: 03.41
ORCID: 0000-0002-9293-0787
SCOPUS ID: 6602181525

The progression of cancer from locally growing to treatment-resistant and metastatic is most often the event responsible for treatment failures. The biology underpinning the fact, that some tumor cells are more resistant to the currently available treatments, or are prone to become invasive, is still poorly understood. The theory of cancer stem cells suggests phenotypic and functional heterogeneity within the primary tumor. Cancer stem cells have been increasingly shown to play an integral role in tumor initiation, disease progression, metastasis and treatment resistance.

Therefore our research is focused on:

  1. defining the cells that initiate tumourigenesis
  2. signaling pathways involved in tumor heterogeneity with the focus on cancer cells with invasive potential
  3. the role of epithelial to mesenchymal transition (EMT) in the regulation of cancer stem cell function and metastasis, and the mechanism responsible for cancer resistance to currently available treatments
  4. the role of microenvironment in the development of the phenotypic and functional diversity of cancer cells

In our experimental approach we are using different molecular and cellular approaches. We are also developing reporter systems combined with lineage tracing to study cancer stem cells, cancer invasion and metastasis as well as cancer heterogeneity in primary mouse tumor models and in human cancers.

The progression of cancer from locally growing to treatment-resistant and metastatic is most often the event responsible for treatment failures. The biology underpinning the fact, that some tumor cells are more resistant to the currently available treatments, or are prone to become invasive, is largely unknown. The theory of cancer-initiating cells suggests phenotypic and functional heterogeneity within the primary tumor. Cancer-initiating cells have been increasingly shown to play an integral role in tumor initiation, disease progression, metastasis and treatment resistance. Therefore, our laboratory’s goal is to understand signaling pathways on a molecular level, as well as the molecules involved in tumor heterogeneity. We are also interested in the role of microenvironment in the development of the phenotypic and functional diversity of tumor cells. In our experimental approach, we use tools of molecular biology, tumor mouse models, functional genomics, and in vivo imaging.

Leader

Major Areas of Research Interest

Adult stem cells
Cancer Stem cells
Cancer heterogeneity
Invasion and metastasis of Cancer
Tumor microenvironment

Education and degrees

1997        M.Sc. (Molecular Biology), University of A. Mickiewicz, Poznan, Poland
2000        Ph.D. (Biology – Molecular Genetics), K. Marcinkowski University of Medical Sciences, Poznan (Poland),

Professional background

2015-current: Group leader, Laboratory of the Molecular Biology of Cancer
Center of New Technologies, University of Warsaw, Warsaw, Poland

2007-2015: Assistant Professor of Otolaryngology and Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine
Norris Cancer Center, Los Angeles, CA, USA

2002-2007: Postdoctoral Associate, The Rockefeller University, Laboratory of Mammalian Cell Biology and Development, New York, NY, USA

2001-2002: Postdoctoral Associate, University of Chicago, Department of Molecular Genetics and Cell Biology, Chicago, IL, USA

1999-2000: Assistant, Department of Biochemistry and Molecular Biology, K. Marcinkowski University of Medical Sciences, Poznan, Poland,

1997-1999: Doctoral student, Department of Biochemistry and Molecular Biology, K. Marcinkowski University of Medical Sciences, Poznan, Poland,

Honors and Awards

ESHG Scholarship for Young Researcher, 31th Annual Meeting of the European Society of Human Genetics, Geneva, Switzerland, 1999

FEBS Scholarship for Young Researcher, 26th Meeting of the Federation of European Biochemical Societies Nice, France, 1999

Scientific Research Award for doctoral student, Polish State Committee (KBN), Poznan, Poland

Mozolowski’s First Prize for the best paper presented by a doctoral student at the 35th Meeting of the Polish Biochemical Society, Olsztyn, Poland, 1999

An Award from the President of K. Marcinkowski University of Medical Sciences for the best Ph.D. thesis, Poznan, Poland, 2000

FEBS Scholarship for Young Researcher, 18th International Congress of Biochemistry and Molecular Biology, Birmingham, UK, 2000

American Cancer Society, Pilot Grant for New Investigator, 2007

Robert E. and May R. Wright Foundation Award, 2008

Stop Cancer, Research Career Development Award, 2009

Margaret Early Medical Research Trust, 2010

Team

Leader
Prof. Agnieszka Kobielak

Postdoctoral Fellows
Chathurika Gamage, PhD

PhD Students
Megha Gautam, MSc
Tomasz Buko, MSc
Manish Poojary, MSc

Students
Kacper Nowak, BS
Dominika  Krasoń

Selected projects

Title Leader Years Funding
Defining the transcriptional and epigenetic state of tumor cells with increased plasticity and the epithelial-endothelial transition and their role in vascular mimicry, circulating tumor cell formation, and breast cancer metastasis A. Kobielak 2024-2028 NCN OPUS
Transcriptional and functional characterization of invasive breast cancer cells isolated using novel in vivo reporter system A. Kobielak 2021-2026 NCN OPUS
Profiling of Breast Cancer Circulating Tumor Cells using single cell RNA sequencing M. Gielata 2021-2024 NCN PRELUDIUM
Defining the contribution of Bmi1-positive oral epithelial stem cells in the process of tumorgenesis using lineage tracing analysis system and role of Bmi1 protein in cells derived from head and neck squamous cell carcinoma K. Karpińska 2020-2023 NCN PRELUDIUM
Role of catulin in the regulation of cell-extracellular matrix interactions in tumor invasion and metastasis of head and neck squamous cell carcinoma. A. Kobielak 2018-2022 NCN OPUS
Understanding cancer stem cell heterogeneity and plasticity and its role in the progression of oral cancer. A. Kobielak 2016-2020 NCN OPUS
Działanie 1.1. RPO Mazowsze – Wzmocnienie sektora badawczo-rozwojowego 2014-2015 RPO WM

Selected publications

  • Catulin reporter marks a heterogeneous population of invasive breast cancer cells with some demonstrating plasticity and participating in vascular mimicry. Gielata M, Karpińska K, Gwiazdowska A, Boryń Ł, Kobielak A. Sci Rep. 2022 Jul 25;12(1):12673. doi: 10.1038/s41598-022-16802-2.
  •  Emerging Roles of the α-Catenin Family Member α-Catulin in Development, Homeostasis and Cancer ProgressionGielata M, Karpińska K, Pieczonka T, Kobielak A. Int J Mol Sci. 2022 Oct 8;23(19):11962. doi: 10.3390/ijms231911962.
  • Catulin Based Reporter System to Track and Characterize the Population of Invasive Cancer Cells in the Head and Neck Squamous Cell CarcinomaKarpińska K, Gielata M, Gwiazdowska A, Boryń Ł, Kobielak A. Int J Mol Sci. 2021 Dec 23;23(1):140. doi: 10.3390/ijms23010140.
  •  Alpha-Catulin, a New Player in a Rho Dependent Apical Constriction That Contributes to the Mouse Neural Tube Closure. Karpińska K, Cao C, Yamamoto V, Gielata M, Kobielak A. Front Cell Dev Biol. 2020 Mar 17;8:154. doi: 10.3389/fcell.2020.00154
  • GRP78 haploinsufficiency suppresses acinar-to-ductal metaplasia, signaling, and mutant Kras-driven pancreatic tumorigenesis in mice. Shen J, Ha DP, Zhu G, Rangel DF, Kobielak A, Gill PS, Groshen S, Dubeau L, Lee AS. Proc Natl Acad Sci U S A. 2017 May 16;114(20):E4020-E4029. doi: 10.1073/pnas.1616060114
  • Efficient Assessment of Developmental, Surgical and Pathological Lymphangiogenesis Using a Lymphatic Reporter Mouse and Its Embryonic Stem Cells. Hong M, Jung E, Yang S, Jung W, Seong YJ, Park E, Bramos A, Kim KE, Lee S, Daghlian G, Seo JI, Choi I, Choi IS, Koh CJ, Kobielak A, Ying QL, Johnson M, Gardner D, Wong AK, Choi D, Hong YK. PLoS One. 2016 Jun 9;11(6):e0157126. doi: 10.1371/journal.pone.0157126
  • Lgr5 Marks Neural Crest Derived Multipotent Oral Stromal Stem Cells. Boddupally K, Wang G, Chen Y, Kobielak A. Stem Cells. 2016 Mar;34(3):720-31. doi: 10.1002/stem.2314
  • Defining the localization and molecular characteristic of minor salivary gland label-retaining cellsZhang H, Boddupally K, Kandyba E, Kobielak K, Chen Y, Zu S, Krishnan R, Sinha U, Kobielak A. Stem Cells. 2014 Aug;32(8):2267-77. doi: 10.1002/stem.1715
  • α-Catulin marks the invasion front of squamous cell carcinoma and is important for tumor cell metastasis. Cao C, Chen Y, Masood R, Sinha UK, Kobielak A. Mol Cancer Res. 2012 Jul;10(7):892-903. doi: 10.1158/1541-7786.MCR-12-0169
  • Governing epidermal homeostasis by coupling cell-cell adhesion to integrin and growth factor signaling, proliferation, and apoptosis. Livshits G, Kobielak A, Fuchs E. Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):4886-91. doi: 10.1073/pnas.1202120109
  • Links between alpha-catenin, NF-kappaB, and squamous cell carcinoma in skin. Kobielak A, Fuchs E. Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2322-7. doi: 10.1073/pnas.0510422103
  •  Alpha-catenin: at the junction of intercellular adhesion and actin dynamics. Kobielak A, Fuchs E. Nat Rev Mol Cell Biol. 2004 Aug;5(8):614-25. doi: 10.1038/nrm1433
  • Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables. Kobielak A, Pasolli HA, Fuchs E. Nat Cell Biol. 2004 Jan;6(1):21-30. doi: 10.1038/ncb1075

Contact

Prof. Agnieszka Kobielak
e-mail: a.kobielak@cent.uw.edu.pl
phone: +48 22 55 43735
room: 03.41