HUMANIZED YEAST CELL SYSTEM

The high degree of conservation of cellular processes and molecular pathways between yeast and human cells, has made Saccharomyces cerevisiae a powerful model system to study human proteins and molecular mechanisms underlying the pathobiology of several human diseases, largely contributing to the discovery of new therapeutic opportunities.

If the gene of interest is conserved in yeast, its function can be directly studied in this organism. However, if the gene has no orthologues in yeast, its study is still possible by heterologous expression. This so-called humanized yeast model has been widely used by our group for biological and pharmacological studies of human proteins with a key role in cancer progression, such as protein kinase C (PKC) isoforms, caspases, p53 family proteins (wild type and mutant p53, p63, p73) and the oncoproteins MDM2 and MDMX (Reviewed in Pereira et al., FEBS J 2012; Pereira et al., Curr Pharm Des 2012).

In the last years, valuable data about the biology of cancer-related human proteins has been provided by our research group using yeast. Additionally, innovative yeast target-directed screening approaches were developed, and have revealed to be powerful tools in the discovery of new therapeutic opportunities against cancer.

HUMAN TUMOR CELL LINES

Our group explores the in vitro molecular mechanism of action and the anticancer properties of compounds identified in yeast, using human tumor cell lines. We analyse the biological activity of the discovered compounds alone or in combination with known anticancer drugs. Determination of cell viability and proliferation, apoptosis, cell cycle arrest, migration, and invasion, are some examples of the analysis performed in human tumor cells.

ANIMAL MODELS

Our group also performs in vivo assays, using xenograft mice models for in vivo validation of the antitumor properties of promising anticancer agents. The subsequent analysis of tumor tissues is also performed by immunohistochemistry.