Pierre Galka

Cyclic peptides mediated genes regulation

The regulation of gene expression is one of the most exciting and enigmatic processes involved at all steps of cellular life, especially during normal or abnormal cell differentiation and proliferation. For this principal reason, it is extensively studied in developmental and oncologic contexts.

The oncogenic character of protein Pbx1a (PreB-cell leukemia transcription factor 1a) is well established and suggests its implication not only in leukemia but also in numerous other cancers (pancreas, liver, breast or prostate). This ubiquitous implication in cancers together with our bioinformatics analyses showing 100% conservation in mammalian sequences of Pbx1a suggest a hub position of the protein in transcriptional events of normal cell development and cancerogenesis.

Started in January 2012, our research project aims at developing a new method for interfering with transcriptional regulation by screening millions of biosynthetic cyclic peptides obtained with an intein-based method. The principal work hypothesis is that some peptides in these genetic libraries can act as disruptors of the ternary transcriptional enhancer complex formed between Pbx1a, its cofactor protein Hoxa1 and a specific target DNA sequence (HoxB1-Auto Regulatory Element).

We develop also new cyclic peptide based approaches for other clinical targets with poor prognosis in the frame of collaborations with other teams interested by innovative technologies.