Alexander Kagansky

The University of Edinburgh | UoE · School of Biological Sciences

Glioma is a devastating brain tumor with a high mortality rate attributed to the glioma stem cells (GSCs) possessing high plasticity. Marker mutations in isocitrate dehydrogenase type 1 (IDH1) and tumor protein 53 (TP53) are frequent in gliomas and impact the cell fate decisions. Understanding the GSC heterogeneity within IDH1- and TP53- mutant tum...

Understanding the mechanisms that regulate cancer progression is pivotal for the development of new therapies. Although p53 is mutated in half of human cancers, its family member p73 is not. At the same time, isoforms of p73 are often overexpressed in cancers and p73 can overtake many p53 functions to kill abnormal cells. According to the latest st...

During oncogenesis, cells become unrestrictedly proliferative thereby altering the tissue homeostasis and resulting in subsequent hyperplasia. This process is paralleled by resumption of cell cycle, aberrant DNA repair and blunting the apoptotic program in response to DNA damage. In most human cancers these processes are associated with malfunction...

According to the World Health Organization, the population of over 60 will double in the next 30 years in the developed countries, which will enforce a further raise of the retirement age and increase the burden on the healthcare system. Therefore, there is an acute issue of maintaining health and prolonging active working longevity, as well as imp...

The third author’s given name was incomplete in the initial online publication.

This paper aims to help policy makers with a characterization of the intrinsic value of biodiversity and its role as a critical foundation for sustainable development, human health, and well-being. Our objective is to highlight the urgent need to overcome economic, disciplinary, national, cultural, and regional barriers, in order to work out innova...

The origin of glial macrophages and their role in pathology is debated (Gutmann and Kettenmann 2019). In gliomas, paired TP53/IDH1 mutations are associated with lower immune infiltration and better outcomes (Cancer Genome Atlas Research Network et al. 2015) (Amankulor et al. 2017). In contrast, within isocitrate dehydrogenase 1 (IDH1) non-mutant gl...

With about 25% of life-saving pharmaceutical drugs derived from plants, unexplored flora offer much promise as a source of new pharmacologically active molecules. Despite the number of challenges associated with plants as a drug discovery source, the thousands to millions of different molecules that plants produce cannot be disregarded in the wake...

The evaluation of herbal extracts’ toxicity profiles are crucial when validating their therapeutic potential. Hence, an in vitro model using embryonic dorsal aorta region from day 11 mice embryo and cKit+ cells from B6 mice bone marrow was used to evaluate the hematotoxicity of three Mauritian endemic medicinal plants. At high concentration, all th...

Biological diversity sustains humanity. It is the nature of the evolutionary process for biodiversity to wax and wane over time, but biodiversity is currently declining at rates undocumented in human history and anthropogenic activities are the primary drivers of biodiversity losses. A variety of solutions have been proposed as means to protect nat...

Terrestrial plants have contributed massively to the development of modern oncologic drugs. Despite the wide acceptance of Mauritian endemic flowering plants in traditional medicine, scientific evidence of their chemotherapeutic potential is lacking. This study aimed to evaluate the in vitro tumor cytotoxicity of leaf extracts from five Mauritian e...

Increasing prevalence of antibiotic resistance has led research to focus on discovering new antimicrobial agents derived from the marine biome. Although ample studies have investigated sponges for their bioactive metabolites with promising prospects in drug discovery, the potentiating effects of sponge extracts on antibiotics still remains to be ex...

The balance between acetylation and deacetylation of histone proteins plays a critical role in the regulation of genomic functions. Aberrations in global levels of histone modifications are linked to carcinogenesis and are currently the focus of intense scrutiny and translational research investments to develop new therapies, which can modify compl...

Isolated cases of experimental evidence over the last few decades have shown that, where specifically tested, both prokaryotes and eukaryotes have specific lipid species bound to nucleoproteins of the genome. In vitro, some of these lipid species exhibit stoichiometric association with DNA polynucleotides with differential affinities toward certain...

Epigenetic silencing is the reversible inactivation of a gene transcription which occurs as a result of changes in the structure of the chromatin that can be successfully inherited from parent to daughter cells. It involves non-genetic mutations within the genome, as well as post-transcriptional and post-translational mechanisms. Existence of these...

Isolated cases of experimental evidence over the last few decades have shown that, where specifically tested, both prokaryotes and eukaryotes have specific lipid molecules bound to nucleoproteins of the genome. In vitro, some of these lipids exhibit stoichiometric association with DNA polynucleotides with differential affinities towards certain sec...

Isolated cases of experimental evidence over the last few decades have shown that, where specifically tested, both prokaryotes and eukaryotes have specific lipid molecules bound to nucleoproteins of the genome. In vitro, some of these lipids exhibit stoichiometric association with DNA polynucleotides with differential affinities toward certain seco...

Posttranslational histone modifications are believed to allow the epigenetic transmission of distinct chromatin states, independently of associated DNA sequences. Histone H3 lysine 9 (H3K9) methylation is essential for heterochromatin formation; however, a demonstration of its epigenetic heritability is lacking. Fission yeast has a single H3K9 meth...

Heterochromatin underpins gene repression, genome integrity and chromosome segregation. In the fission yeast, Schizosaccharomyces pombe, conserved protein complexes effect heterochromatin formation via RNA interference-mediated recruitment of a histone H3 lysine 9 methyltransferase to cognate chromatin regions. To identify small molecules that inhi...

Human kinetochores are transcriptionally active, producing very low levels of transcripts of the underlying alpha-satellite DNA. However, it is not known whether kinetochores can tolerate acetylated chromatin and the levels of transcription that are characteristic of housekeeping genes, or whether kinetochore-associated 'centrochromatin', despite b...

HIRA (or Hir) proteins are conserved histone chaperones that function in multi-subunit complexes to mediate replication-independent nucleosome assembly. We have previously demonstrated that the Schizosaccharomyces pombe HIRA proteins, Hip1 and Slm9, form a complex with a TPR repeat protein called Hip3. Here we have identified a new subunit of this...

In fission yeast, RNAi directs heterochromatin formation at centromeres, telomeres, and the mating type locus. Noncoding RNAs transcribed from repeat elements generate siRNAs that are incorporated into the Argonaute-containing RITS complex and direct it to nascent homologous transcripts. This leads to recruitment of the CLRC complex, including the...

RNA interference (RNAi) is widespread in eukaryotes and regulates gene expression transcriptionally or post-transcriptionally. In fission yeast, RNAi is tightly coupled to template transcription and chromatin modifications that establish heterochromatin in cis. Exogenous double-stranded RNA (dsRNA) triggers seem to induce heterochromatin formation...

The formation of heterochromatin at the centromeres in fission yeast depends on transcription of the outer repeats. These transcripts are processed into siRNAs that target homologous loci for heterochromatin formation. Here, high throughput sequencing of small RNA provides a comprehensive analysis of centromere-derived small RNAs. We found that the...

Synthetic Centromere Every eukaryotic chromosome must have a centromere where the cell division machinery latches onto each chromosome pair to ensure an even apportioning of the genetic material between daughter cells. The characteristic (but not conserved) repeat sequences associated with most centromeres are thought to be required to induce an RN...

The mechanisms ensuring specific incorporation of CENP-A at centromeres are poorly understood. Mis16 and Mis18 are required for CENP-A localization at centromeres and form a complex that is conserved from fission yeast to human. Fission yeast sim1 mutants that alleviate kinetochore domain silencing are defective in Scm3(Sp), the ortholog of budding...

Heterochromatin formation at fission yeast centromeres is directed by RNA interference (RNAi). Noncoding transcripts derived from centromeric repeats are processed into small interfering RNAs (siRNAs) that direct the RNA-induced transcriptional silencing (RITS) effector complex to engage centromere transcripts, resulting in recruitment of the histo...

Cohesin, an SMC (structural maintenance of chromosomes) protein-containing complex, governs several important aspects of chromatin dynamics, including the essential chromosomal process of sister chromatid cohesion. The exact mechanism by which cohesin achieves the bridging of sister chromatids is not known. To elucidate this mechanism, we reconstit...

Genetic analysis of RecA protein chimeras and their ancestors, RecAEc (from Escherichia coli) and RecAPa (Pseudomonas aeruginosa) had allowed us to place these proteins with respect to their recombinogenic activities in the following order: RecAPa>RecAX21>RecAX20=RecAEc. While RecAX20 differs from RecAEc in five amino acid residues with two substit...