Saba Saitidze

Another direction of research interest is the role of the disruption of cell-cycle control and of genomic instability in malignant transformation.

Particular attention is paid to the functions of the genes TP53/p53, RB1, PTEN, APC, BRCA1 and BRCA2 and of their protein products.

The main topics of interest are:

• the transcriptional activity of p53, MDM2-dependent regulation and the cellular programmes that respond to DNA damage;
• the ATM–ATR–CHK1/CHK2 signalling pathways and the cell-cycle checkpoints;
• homologous recombination, non-homologous end joining (NHEJ) and defects in DNA repair;
• replication stress, chromosomal instability and telomere dysfunction;
• the use of synthetic lethality to identify the selective vulnerability of tumour cells.

Of significant scientific interest is how a tumour cell changes gene expression even without altering the primary nucleotide sequence of DNA.

In this direction particular attention is paid to DNA methylation, histone acetylation and methylation, chromatin remodelling, functional defects of the SWI/SNF complexes and the role of epigenetic enzymes in oncogenesis.

The field of interest includes DNMT, HDAC, EZH2 and the BET family proteins, as well as the participation of non-coding RNAs, microRNAs and long non-coding RNAs in the transcriptional regulation of tumour cells.

Saba's scientific interests extend to the metabolic reprogramming of tumour cells, with particular emphasis on the interrelationship between energy metabolism and oncogenic signalling.

The research topics are aerobic glycolysis and the Warburg effect, glutaminolysis, anaplerotic reactions of the tricarboxylic acid cycle, the pentose phosphate pathway, one-carbon metabolism and NADPH-dependent redox homeostasis.

Of special interest is the role of the regulatory systems HIF-1α, AMPK, mTORC1, MYC and NRF2 in metabolic adaptation, as well as the connection of mitochondrial reactive oxygen species, glutathione metabolism and lipid peroxidation with tumour progression.

The research interests include the molecular mechanisms of programmed cell death and the biochemical processes whose disruption gives tumour cells a survival advantage.

Particular attention is paid to mitochondrial apoptosis, the anti-apoptotic and pro-apoptotic proteins of the BCL-2 family, BAX/BAK-dependent permeabilisation of the mitochondrial membrane, the release of cytochrome c and the activation of the caspase cascade.

An additional field of interest is the function of the GPX4–GSH system, SLC7A11-dependent cystine transport, iron-dependent lipid peroxidation and the therapeutic potential of ferroptosis against resistant tumours.