Laboratory of Molecular Bases of Aging

Head: Ewa Sikora

 

Degrees:

2002 Professor of Biological Sciences, nomination by the President of the Republic of Poland, Nencki Institute of Experimental Biology, PAS

1998 DSc Habil, Nencki Institute of Experimental Biology, PAS

1983 PhD in Biology, Nencki Institute of Experimental Biology, PAS

1977 MSc in Biology, University of Warsaw

 

Professional employments:

2003 Professor Nencki, Institute of Experimental Biology, PAS

1999 Associate Professor, Nencki Institute of Experimental Biology, PAS

1995 Contract Professor of University of Modena, Italy

1983 Assistant Professor (adjunct), Nencki Institute of Experimental Biology, PAS

1981 Assistant, Nencki Institute of Experimental Biology, PAS

 

Honors and fellowships:

2009 Polonia Restituta

2007 The award of Polish Academy of Sciences for a series of papers:„Molecular Mechanisms of cellular senescence and cell death”

1996 Godeski  Visiting Professorship at Cross Cancer Institute, Edmonton, Canada

1994 UNESCO stipend for training at the University of Modena School of Medicine, Modena, Italy

1992-1993 FEBS fellowship for training at the University of Modena School of Medicine, Modena, Italy

1986-1987 Postdoctoral fellowship of National Union Against Cancer for postdoc position in Institute of Cancer Research, Sutton, Surrey, England

Staff: Anna Bielak-Żmijewska, Agnieszka Bojko, Agata Ciołko (PhD student), Joanna Czarnecka (PhD student), Magdalena Dąbrowska, Magdalena Dudkowska, Wioleta Grabowska (PhD student), Dorota Janiszewska, Anna Karpa, Karolina Kucharewicz (PhD student), Grażyna Mosieniak, Anna Strzeszewska (PhD student), Piotr Sunderland (PhD student)

 

Research profile:

 

We are interested in the molecular mechanisms of cell senescence, which is considered as an irreversible arrest of cell proliferation involved in normal and pathological ageing of the organism. Senescent cells remain alive and metabolically active. They secrete a mix of molecules which can influence other cells. We are interested whether these molecules are secreted in exosomes and how they change the function of the immune cells. Senescent cells can also communicate with other cells by cytoplasmic bridges which are of our interest. We study the mechanisms of cell autophagy and its molecular and functional connection with cell senescence. DNA double strand breaks (DSBs) triggers a signaling and effector pathway known as the DNA damage response (DDR) that coordinates cell-cycle arrest and DNA repair. It is believed that persistent DDR signaling establishes cellular senescence. Our studies indicate that this paradigm is not valid in some models of cell senescence. Moreover, ATM the key protein of DDR can still have unrecognized role in DDR-independent senescence as well as senescence of non-dividing post-mitotic (neuronal) cells. In senescing human VSMCs we aim to dissect the role of epigenetic modification and compaction of chromatin. Cell senescence can be also induced in cancer cells as an outcome of anticancer treatment. As we showed previously that the process of cancer cell senescence can be reversible we are interested in dissecting the mechanisms of divisions of cancer cells induced to senescence and the role of polyploidy and stemness in this process.

 

Current research activities:

 

The projects are aimed to dissect:

  • the role of senescence induced secretory phenotype (SIPS) of senescing human vascular smooth muscle cells (VSMCs) in modulating of the immune cell function,
  • the  role  of  chromatin  modulation  in  normal  cell senescence ( VSMCs, human skin fibroblasts),
  • the role of cytoskeletal proteins in direct communication between human senescent cells (VSMCs),
  • the influence of natural polyphenol, curcumin on DNA damage and  its role in senescence of normal and cancer cells,
  • the role of DNA damage and DNA damage response (DDR) in senescence, autophagy and cell death of rodent neurons and human iPSCs,
  • mechanisms of cell senescence and induction of secretory phenotype in cancer cells with non-functional DDR, particularly due to the lack of the functional p53 protein,
  • the interconnection between senescence, polyploidy and stemness of cancer cells,
  • the mechanisms of autophagy  regulation by tacrin- -melatonin derivatives in normal and cancer cells,
  • the role of the immune system and inflammaging in healthy and unhealthy ageing,
  • the influence of novel agents targeting telomeres on cancer and normal cell fate.

 

Selected publications:

 

Piechota M., Sunderland P., Wysocka A., Nalberczak M., Śliwińska M.A., Radwańska K., Sikora E. (2016) Is senescence-associated β-galactosidase a marker of neuronal senescence? Oncotarget, 7(49): 81099-81109.

 

Przybylska D., Janiszewska D., Goździk A., Bielak-Żmijewska A., Sunderland P., Sikora E., Mosieniak G. (2016) NOX4 downregulation leads to senescence of human vascular smooth muscle cells. Oncotarget, 7(41): 66429-66443.

 

Grabowska W., Suszek M., Wnuk M., Lewińska A., Wasiak E., Sikora E., Bielak-Zmijewska A. (2016) Curcumin elevates sirtuin level but does not postpone in vitro senescence of human cells building the vasculature. Oncotarget, 7(15): 19201-19213.

 

Mosieniak G., Śliwinska M.A., Przybylska D., Grabowska W., Sunderland P., Bielak-Zmijewska A., Sikora E. (2016) Curcumin-treated cancer cells show mitotic disturbances leading to growth arrest and induction of senescence phenotype. Int J Biochem Cell Biol, 74: 33-43.

 

Mosieniak G., Śliwinska M.A., Alster O., Strzeszewska A., Sunderland P., Piechota  M., Was H., Sikora E. (2015) Polyploidy Formation in Doxorubicin-Treated Cancer Cells Can Favor Escape from Senescence. Neoplasia. 17(12): 882-893.