The Swedish Cancer Foundation, Cancerfonden, has announced the researchers it will be supporting in its most recent round of funding and Lund Stem Cell Center was especially successful, with seven scientists awarded a total of almost 30 million SEK. Cristian Bellodi, a research team leader from the Division of Molecular Hematology, was awarded 12 million SEK - the largest grant to any researcher at Lund University.
“The fundamental question we are trying to address is how genetic information is regulated in stem cells and cancer cells” says Cristian, who’s research focus is on the essential and multifaceted role of Ribonucleic acid, or RNA, the molecule involved in several key steps of gene expression. “It is now becoming evident that chemical modification of RNA plays an essential role in directing gene expression programs involved in the development of lethal human hematological cancers” continues Cristian.
The Bellodi group published an article in the journal Cell last year describing a novel function of pseudouridine, the most abundant RNA modification conserved from bacteria to human, in stem cells that critically impacts the metabolism and differentiation capacity of human embryonic and hematopoietic stem cells (HSCs). The research team discovered that one of the enzymes responsible for the pseudouridine modification of RNA, namely PUS7, decorates previously uncharacterized small non-coding RNA molecules termed miniTOGs (mTOGs). Upon modification, mTOGs become active and control protein production directing the differentiation of stem cells to mature blood cells. It is now emerging that pseudouridine modification of mTOGs may act as a signal within HSCs to “keep in check” the translation machinery and ensuring that the adequate quantity and quality of proteins are produced to allow efficient blood production.
Using the funding awarded by Cancerfonden, Cristian and his research team will dissect another new unanticipated function of PUS7 and mTOGs in cancer. “We have discovered that some signals required for normal hematopoiesis that involve RNA modifications are being co-opted by specific types of cancer to control protein synthesis rates” explains Cristian. “Dysregulation of protein synthesis is central to the process of tumor development, tumorigenesis, and is frequently hijacked by cancer cells to their advantage”.
Targeting protein synthesis could represent an Achilles’ heel to eradicating cancer-initiating cells and be potentially important for life-threatening blood cancers characterised by dysfunctional stem cells. To further study this, Cristian and his research team have developed various genetic models to understand the contribution of RNA modifications at the organismal level during normal development and in cancer.
The Cancerfonden support will be instrumental to further spearhead the exciting new research ongoing in the Bellodi lab that highlights the importance of RNA modifications in directing genetic information in stem and cancer cells. A better understanding of how RNA modifications contribute to disease is of particular significance, as this could potentially lead to the identification of novel biomarkers and therapeutic strategies to target metabolic alterations underlying the etiology of aggressive human haematological cancers, such as leukemia and lymphomas.
Contact: Cristian Bellodi, PhD, Associate senior lecturer, Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Lund University
Email: cristian [dot] bellodi [at] med [dot] lu [dot] se
Job Opportunity: Postdoctoral position in RNA modifications, Hematopoiesis and Cancer within the Bellodi group.
This project is funded by Cancerfonden, The Swedish Foundations’ Starting Grant (SFSG), StemTherapy & Vetenskapsrådet. Cristian Bellodi is also a Ragnar Söderberg Researcher in Medicine and a recipient of the Cancer Fund Young Investigator Award.