Christian Bellodi

Project summary

Regulatory RNA and leukaemia. Elucidating the role of H/ACA small non-coding RNAs in leukaemogenesis.

Cristian Bellodi investigates how fundamental processes of gene expression operate within cells and how they may contribute to the development of leukaemia. He studies small non-coding RNAs and their role in protein production. In the long term, the research may contribute to the development of new diagnostic tools and treatments for certain types of leukaemia.

 

Abnormal regulation of a common class of non-coding nucleic acid molecules known as H/ACA small RNAs is emerging as a recurrent feature of blood cancers. H/ACA small RNAs bind to key proteins to generate hundreds of active small particles, known as H/ACA small ribonucleoproteins (RNPs), which play an important role in the cellular processes that translate genetic information into proteins. One of the main proteins bound by H/ACA small RNAs is mutated in severe human syndromes associated with a high risk of blood cancer. An important question is therefore how dysfunction of H/ACA small RNPs contributes to cancer development.

 

This project investigates the mechanisms through which dysregulation of H/ACA small RNPs impairs a cellular fail-safe mechanism known to halt the growth of cancer cells: oncogene-induced senescence (OIS). Escaping OIS is a critical step in tumour development. My preliminary data suggest that H/ACA small RNPs are modulated during OIS and regulate the production of factors that are frequently altered in blood cancers associated with haematopoietic stem cells and that affect older people. Using innovative genetic tools, I aim to elucidate the mechanisms through which defective H/ACA small RNPs disrupt gene expression in haematopoietic stem cells during the development of leukaemia.

 

These studies will have broad clinical relevance for the development of new diagnostic tools and treatments for blood cancers characterised by dysfunctional stem cells, which are frequently seen in older people.