CeNT
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Laboratory of the Molecular Biology of Cancer

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. cells of origin of epithelial cancers
  2. signaling pathways involved in tumor heterogeneity with the focus on cancer cells with invasive potential
  3. 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.

 

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

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

 

Major Areas of Research Interest

Adult stem cells

Cancer Stem cells

Cancer heterogeneity

Invasion and metastasis of Cancer

Tumor microenvironment

 

Research Grant

Current:

Opus 13, NCN grant, A. Kobielak (PI)  Role of catulin in the regulation of cell-extracellular matrix interactions in tumor invasion and metastasis of head and neck squamous cell carcinoma. 2018-2021

Opus 9, NCN grant   A. Kobielak (PI)    Understanding cancer stem cell heterogeneity and plasticity and its role in the progression of oral cancer. 2016-2019

 

Completed Research Support:

ACS pilot grant A. Kobielak (PI)    Conditional ablation of cell-cell  junctions component α-catenin in oral  epithelium as a model to study Head and Neck  Squamous Cell Carcinoma. 2007-2008

Wright Foundation Award  A. Kobielak (PI)   Isolation and characterization of normal and cancer oral epithelium stem cells as  a target for future oral epithelium squamous cell carcinoma treatment. 2008-2009

STOP CANCER   A. Kobielak (PI) Characterization of epithelial and stromal compartments during different stages of oral cavity squamous cell cancer progression. 2009-2010

Margaret Early Medical Research Trust, A. Kobielak Characterization of slow-cycling squamous cell carcinoma cells. 2010

1 R21 DE021522-01    NIH/NIDCR    A. Kobielak (PI)    Isolation and characterization of the normal and cancer stem cells of the tongue. 2011 – 2013

Kure It Foundation – research grant 2014 – 2015 A. Kobielak (PI) Characterization of biomarkers of invasion in Head and Neck Squamous Cell Carcinoma.

 

Selected publications:

  1. Shen J., Ha DP., Zhu G., Rangel DF., Kobielak A., Gill PS., Groshen S., Dubeau L., Lee AS., GRP78 haploinsufficiency suppresses acinar-to-ductal metaplasia, signaling, and mutant Kras-driven pancreatic tumorigenesis in mice. PNAS, May 16;114(20) 4020-4029, 2017
  2. 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., Efficient Assessment of Developmental, Surgical and Pathological Lymphangiogenesis Using a Lymphatic Reporter Mouse and Its Embryonic Stem Cells. PLoS One, Jun 9;11(6) 2016
  3. Boddupally K., Chen Y., Kobielak A. Lgr5 marks neural crest derived multipotent oral stromal stem cells. Stem Cells, Mar;34(3):720-31, 2016
  4. Kobielak A. and Boddupally K. Junctions and inflammation in the skin. Cell Comm. and Adhesion,  21(3):141-7; 2014
  5. Zhang H., Boddupally K., Kandyba E., Kobielak K., Chen Y., Zu S., Krishnan R., Sinha U., Kobielak A. Defining the slow cycling stem cells of minor salivary glands: role in gland regeneration and tumor formation. Stem Cells.  32(8):2267-77; 2014
  6. Kandyba E, Hazen V, Kobielak A, Butler J.S, Kobielak K. Smad1&5 but not Smad8 establish stem cell quiescence which is critical to transform the premature hair follicle during morphogenesis towards the postnatal state. Stem Cells.  32(2):534-47; 2014
  7. Masood R, Hochstim C, Cervenka B, Zu S, Baniwal SK, Patel V, Kobielak A, Sinha UK. A novel orthotopic mouse model of head and neck cancer and lymph node metastasis. Oncogenesis, 9;2:e68; 2013
  8. Cao C., Chen Y., Masood R., Sinha U., Kobielak A. Catulin marks the invasive front of squamous cell carcinoma and is important for tumor cell metastasis. Molecular Cancer Research, 10(7):892-903; 2012
  9. Livshits G., Kobielak A., Fuchs E. Governing epidermal homeostasis by coupling cell-cell adhesion to integrin and growth factor signaling, proliferation, and apoptosis. PNAS, 109(13):4886-91; 2012
  10. Kobielak A., Fuchs E. Links between α-catenin, NF-κB and Squamous Cell Carcinoma in skin. PNAS 103(7):2322-2327; 2006
  11. Kobielak A., Fuchs E. -Catenin: At the junction of intercellular adhesion and actin dynamics. Nat. Rev. Mol. Cell Biol. 5(8):614-625; 2004
  12. Kobielak A., Pasolli H.A., Fuchs E. Mammalian Formin1 participates in adherens junctions and polymerization of linear actin cables. Nat. Cell Biol. 6 (1):21-30; 2004

Group Leader:
Prof. Agnieszka Kobielak


PhD students:
Mateusz Gielata, MSc
Kamila Karpińska, MSc

Students:

Kacper Rudzki

Catulin Based Reporter System to Track and Characterize the Population of Invasive Cancer Cells in the Head and Neck Squamous Cell Carcinoma
Kamila Karpińska, Mateusz Gielata, Aleksandra Gwiazdowska, Łukasz Boryń, Agnieszka Kobielak
Int. J. Mol. Sci. 2022, 23(1), 140
EBV load is associated with cfDNA fragmentation and renal damage in SLE patients
Anna Truszewska, Agnieszka Wirkowska, Kamila Gala, Piotr Truszewski, Łucja Krzemień-Ojak, Krzysztof Mucha, Leszek Pączek, Bartosz Foroncewicz
Lupus, Volume: 30 issue: 8, page(s): 1214-1225
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.
Frontiers in Cell and Developmental Biology, 8, 154.
hMTH1 and GPX1 expression in human thyroid tissue is interrelated to prevent oxidative DNA damage
Arczewska, K. D., Krasuska, W., Stachurska, A., Karpińska, K., Sikorska, J., Kiedrowski, M., ... & Czarnocka, B.
DNA repair, 95, 102954
Cell-free DNA profiling in patients with lupus nephritis
Truszewska, A., Wirkowska, A., Gala, K., Truszewski, P., Krzemień-Ojak, Ł., Perkowska-Ptasińska, A., ... & Foroncewicz, B.
Lupus, 29(13), 1759-1772
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.,
PNAS, May 16;114(20) 4020-4029.
Lgr5 marks neural crest derived multipotent oral stromal stem cells.
Boddupally, K., Wang, G., Chen, Y., & Kobielak, A. (2016)
Stem cells, 34(3), 720-731.
Lgr5 marks neural crest derived multipotent oral stromal stem cells.
Boddupally K., Chen Y., Kobielak A.
Stem Cells, Mar;34(3):720-31.
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, Jun 9;11(6) 2016
Junctions and inflammation in the skin.
Kobielak, A., & Boddupally, K. (2014).
Cell communication & adhesion, 21(3), 141-147.
Defining the slow cycling stem cells of minor salivary glands: role in gland regeneration and tumor formation.
Zhang H., Boddupally K., Kandyba E., Kobielak K., Chen Y., Zu S., Krishnan R., Sinha U., Kobielak A. , (2014)
Stem Cells. 32(8):2267-77
Smad1&5 but not Smad8 establish stem cell quiescence which is critical to transform the premature hair follicle during morphogenesis towards the postnatal state.
Kandyba E, Hazen V, Kobielak A, Butler J.S, Kobielak K.
Stem Cells. 32(2):534-47
Defining the slow cycling stem cells of minor salivary glands: role in gland regeneration and tumor formation.
Zhang H., Boddupally K., Kandyba E., Kobielak K., Chen Y., Zu S., Krishnan R., Sinha U., Kobielak A.
Stem Cells. 32(8):2267-77;
Junctions and inflammation in the skin.
Kobielak A. and Boddupally K.
Cell Comm. and Adhesion, 21(3):141-7.
A novel orthotopic mouse model of head and neck cancer and lymph node metastasis.
Masood R, Hochstim C, Cervenka B, Zu S, Baniwal SK, Patel V, Kobielak A, Sinha UK.
Oncogenesis, 9;2:e68
Governing epidermal homeostasis by coupling cell-cell adhesion to integrin and growth factor signaling, proliferation, and apoptosis.
Livshits G., Kobielak A., Fuchs E.
PNAS, 109(13): 4886-91
Catulin marks the invasive front of squamous cell carcinoma and is important for tumor cell metastasis.
Cao C., Chen Y., Masood R., Sinha U., Kobielak A.
Molecular Cancer Research, 10(7):892-903