Research

DNA damage response, ageing, carcinogenesis, cellular senescence

Realization of complex tasks of living organisms depends on information stored in the DNA of their genomes. The loss of this information due to endogenously- or exogenously-induced DNA damage results in disintegration of homeostasis at the cellular and organismal level manifested as diseases and ageing. Demographic trends in developed countries predict that the ageing of population will rapidly become a major social and economic issue as aging is accompanied by a large set of debilitating chronic diseases whose cure burdens health care systems. Aging is thought to be a multifactorial process. One of the factors recently identified to contribute to organismal aging is cellular senescence, a cellular stress response caused predominantly by unrepaired DNA damage. Genetic and pharmacologic manipulations leading to elimination of senescent cells from model organisms increase healthspan and lifespan suppressing the onset and development of age-associated diseases including cancer and neurodegenerative disorders.

The general focus of the laboratory is centered on the mechanisms of genomic instability, DNA repair, DNA damage response, cellular senescence, cancer development and resistance, and ageing.

The specific topics currently investigated are:

  1. role of co-transcriptional RNA:DNA hybrids (R-loops) and transcription-replication interference in replication stress-associated genomic instability;
  2. molecular mechanisms underlying restart of stalled replication forks;
  3. role of PML protein in ribosomal stress and rDNA stability;
  4. role of cytokine signalling in cancer cell reprogramming and resistance;
  5. mechanisms of cellular senescence related to resistance of senescent cells to apoptosis including temporal dynamics of senescent phenotype development; and
  6. design and development of new organ-specific anticancer and antiageing approaches including nanotechnology with focus on solid tumors such as glioblastoma, hematooncologic malignancies and neurodegenerative disorders.

 

 

Last change: September 27, 2019