LABORATORY OF SIGNAL TRANSDUCTION

Head: Tomasz Wilanowski

 

Degrees:

2013 DSc Habil, Nencki Institute of Experimental Biology, PAS

1995 PhD in Biology, Australian National University, Research School of Biological Sciences, Canberra, Australia

1990 MSc in Chemistry, University of Warsaw

 

Professional employments:

2009-present Head to the Laboratory of Signal Transduction, Nencki Institute of Experimental Biology, PAS

1998-2009 Senior Research Officer, Royal Melbourne Hospital, Rotary Bone Marrow Research Laboratories, Melbourne, Australia

1995-1998 Postdoctoral Fellow, Australian National University, Research School of Biological Sciences, Canberra, Australia

 

Honors and fellowships: Patent applications:

Pawlak M, Kikulska A, Wilanowski T, Wesoły J: A method for detecting an increased risk of  developing  renal  cancer  and  a  use  of a genotype variant of the GRHL1 and/or GRHL2 and/or GRHL3 gene. Submission no. P.414469, 23.10.2015 (Poland).

 

Kikulska A, Wilanowski T, Rutkowski P: A method for detecting an increased risk of developing skin cancer and a use of a genotype variant of the GRHL3 gene. Submission no. MI2013A002141, 16.12.2013 (Italy).

Staff: Aleksandra Głowacka, Grzegorz Kotarba, Ewa Krzywińska, Magdalena Pawlak, Agnieszka Taracha (PhD student), Marek Żórawski



Research profile:


The main research interests of Laboratory of Signal Transduction concern signaling pathways in mammalian cells. In particular, we investigate the role of Grainyhead-like (GRHL) transcription factors in signal transduction. This includes regulation of gene expression by these transcription factors; regulation of expression of GRHL genes; and post-translational regulation of activity of the GRHL proteins. These transcription factors are very important in health and disease in humans and animals. They are essential for the functioning of the epidermis and other epithelia, for neural tube closure and wound healing. They are also involved in various types of cancer, including cancers of the breast, skin, kidney, liver, stomach and colon. The GRHL proteins are not merely passive indicators of progression of tumor growth, but they also have a direct influence on the process of carcinogenesis. Their correct functioning is essential for their anti-oncogenic function, therefore mutations which affect the functioning of GRHL transcription factors impair their antitumor roles and thereby increase the risk of cancer in affected people. If the mechanisms regulating functioning of proteins from the GRHL family could be enhanced or inhibited by specific drugs or other chemical compounds, such compounds could then be used to treat specific types of cancer. Furthermore, we do not limit our research interests to the GRHL transcription factors only; we also collaborate with a number of scientific teams studying other proteins involved in signal transduction.

 

Current research activities:

 

We investigate some of the functions of GRHL transcription factors using animal models: mouse and zebrafish. These include their involvement in the development and maintenance of skin barrier and in skin cancer, neural tube closure and wound healing.

We also employ animal models to analyze the role of these proteins in the functioning of the kidneys, in the regulation of blood pressure and heart rate.

We are currently studying the involvement of GRHL tran- scription factors in two types of cancer: non-melanoma skin cancer and clear cell renal cell carcinoma. In these projects we examine tumor samples obtained from cancer patients.

We investigate the mechanisms responsible for the reg- ulation of expression of GRHL genes and post-translational regulation of the activity of GRHL proteins. We carry out these experiments in cultured human cells.

We discovered that certain mutations in the genes from the GRHL family occur with significantly altered frequencies in patients with skin cancer or kidney can- cer. We would like to use this information to identify people with increased risk of cancer. Such people could then take appropriate steps to protect them- selves from the disease; for example, in the case of skin cancer they could avoid excessive sunbathing. Such people could also have regular check-ups, as early diagnosis greatly increases the chances of successful treatment of cancer.



Selected publications:

 

Krzywinska E, Zorawski MD, Taracha A, Kotarba G, Kikulska A, Mlacki M, Kwiatkowska K, Wilanowski T (2018) Threonine 454 phosphorylation in Grainyhead-like 3 is important for its function and regulation by the p38 MAPK pathway. Biochimica et Biophysica Acta 1865: 1002-1011
 

Kotarba G, Krzywinska E, Grabowska AI, Taracha A, Wilanowski T (2018) TFCP2/TFCP2L1/UBP1 transcription factors in cancer. Cancer Letters 420: 72-79
 

Kikulska A, Rausch T, Krzywinska E, Pawlak M, Wilczynski B, Benes V, Rutkowski P, Wilanowski T (2018) Coordinated expression and genetic polymorphisms in Grainyhead-like genes in human non-melanoma skin cancers. BMC Cancer 18: 23
 

Pawlak M, Kikulska A, Wrzesinski T, Rausch T, Kwias Z, Wilczynski B, Benes V, Wesoly J, Wilanowski T (2017) Potential protective role of Grainyhead-like genes in the development of clear cell renal cell carcinoma. Molecular Carcinogenesis 56: 2414-2423
 

Mlacki M, Darido C, Jane SM, Wilanowski T (2014) Loss of Grainy head-like 1 is associated with disruption of the epidermal barrier and squamous cell carcinoma of the skin. PLoS One 9: e89247