Prof. Tom (Thomas) Moss has been a member of the Department of Molecular Biology, Medical Biochemistry and Pathology (formally the Department of Biochemistry) at the Laval University School of Medicine since he was recruited from the University of Portsmouth (UK) in 1986. Concurrently, he became Principal Investigator (PI) in the Laval University Cancer Research Centre and is now PI in the St-Patrick Research Group in Basic Oncology and in the Division of Oncology of the Québec University Hospital Research Centre. Originally from Portsmouth, Southern England, Prof. Moss obtained a BSc (hon.) in Applied Physics and a Doctorate in Biophysics from the University of Portsmouth. He went on to study gene regulation at the Institute of Molecular Biology of Zürich University, before returning to Portsmouth as Senior Lecturer and establishing his first laboratory there. His career has been marked by many important discoveries starting in the late ‘70s and early ‘80s, and he is recognized as a leading international expert in his field. Prof. Moss has received several personal awards over the course of his career, including EMBO and Medical Research Council (MRC)-UK Fellowships and MRC-Canada and FRSQ Scholarships, and was nominated as Scientist of the MRC-Canada and as Research Director of the CNRS-France.
The ribosome, genetic diseases, and cancer
The ribosome is responsible for decoding our genetic material and is the cell’s sole means to make protein. It is also the largest “enzyme” known, hence the effort required to make the 3 to 4 million ribosomes in each human cell is a severe limitation to growth. To grow, cancer cells must increase their production of ribosomes, a process known as Ribosome Biogenesis, and this makes them metabolically vulnerable. Oncogenes such as MYC and RAS render cells sensitive to so-called Nucleolar Stress, a surveillance pathway that links decreased fidelity of Ribosome Biogenesis to the central tumour suppressor p53 (TP53), and this increases their sensitivity to cytotoxic drugs. Some new anticancer drugs take advantage of this, e.g. BMH21 and CX5461, and are now showing some promise in clinical settings. However, our data also suggests that several existing cytotoxic drugs, such as cisplatin already target Ribosome Biogenesis. Further, we have recently shown that a genetic block Ribosome Biogenesis causes highly penetrant, p53-independent cell death of cancer cells, while leaving normal cells unaffected. This strongly suggests that drug targeting of Ribosome Biogenesis will offer some important new cancer treatments in the future.
The ribosome is itself made up two-thirds of RNA and only one-third of protein. In humans, the ribosomal RNAs are produced from 400 genes that form megabase tandem arrays at the Nucleolus Organizer Regions (NORs) of the short arms of 5 acrocentric chromosomes. The transcription of these genes creates the nucleoli, the cell’s ribosome factories in each cell nucleus, and the size of these nucleoli is a reliable marker of aggressive tumours. Transcription of the ribosomal RNA genes generates the 47S precursor that is first assembled into pre-ribosomal particles, then processed into the mature RNAs and the subunits of the ribosome. This process of Ribosome Biogenesis involves several hundred small non-coding RNAs and many hundreds of proteins. Mutations in the genes for these ribosomal proteins are responsible for a range of genetic diseases together known as Ribosomopathies, e.g. Diamond-Blackfan anemia (DBA), Dyskeratosis congenita (DC), etc. Ribosomal RNA genes are also involved in the chromosomal translocations that cause Down’s Syndrome, Uniparental Disomy, etc. These so-called “Robertsonian” translocations are also tightly linked to a range of cancers. One area of Dr. Moss’s work is to try to understand the role ribosomal RNA gene silencing plays in preventing these chromosomal translocations. Surprisingly, we discovered this silencing is completely absent in the earliest cells of the embryo, the Embryonic Stem Cells (ESCs), as well as in some cancer cells. We hypothesize that loss of ribosomal RNA gene silencing answers the enhanced metabolic needs of both embryonic and precancerous cells, but also increases the genome instability that drives the evolution of cancer. We are seeking ways to test this experimentally and hence to understand how normal cells are subverted in cancer, as well as the role that cancer stem cells play in this process.
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Metabolic Labeling in the Study of Mammalian Ribosomal RNA Synthesis.Journal Article
Methods Mol Biol, 1455 , 2016.
Depletion of the cisplatin targeted HMGB-box factor UBF selectively induces p53-independent apoptotic death in transformed cells.Journal Article
Oncotarget, 6 (29), 2015.
A novel role for the Pol I transcription factor UBTF in maintaining genome stability through the regulation of highly transcribed Pol II genes.Journal Article
Genome Res, 25 (2), 2015.
Extended Synaptotagmin Interaction with the Fibroblast Growth Factor Receptor Depends on Receptor Conformation, Not Catalytic Activity.Journal Article
J Biol Chem, 290 (26), 2015.
In Vitro DNase I Footprinting.Journal Article
Methods Mol Biol, 1334 , 2015.
The Cruciform DNA Mobility Shift Assay: A Tool to Study Proteins That Recognize Bent DNA.Journal Article
Methods Mol Biol, 1334 , 2015.
Conditional inactivation of Upstream Binding Factor reveals its epigenetic functions and the existence of a somatic nucleolar precursor body.Journal Article
PLoS Genet, 10 (8), 2014.
Loss of Extended Synaptotagmins ESyt2 and ESyt3 does not affect mouse development or viability, but in vitro cell migration and survival under stress are affected.Journal Article
Cell Cycle, 13 (16), 2014.
Meeting report for Odd Pols 2012.Journal Article
Gene, 526 (1), 2013.
The endocytic adapter E-Syt2 recruits the p21 GTPase activated kinase PAK1 to mediate actin dynamics and FGF signalling.Journal Article
Biol Open, 1 (8), 2012.
- Mechanism of Ribosomal RNA Gene Silencing and Its Roles in Pluripotency and Cancer, from 2017-04-01 to 2022-03-31
- Pathobiology and treatment of the UBTF E210K neuroregression syndrome, from 2021-07-01 to 2026-06-30
- Role of Misshappen (NIK/Msn) kinases and Extended-Synaptotagmins (E-Syts) in Wnt and FGF intracellular signaling pathways., from 2017-04-01 to 2022-03-31
Recently finished projects
- Efficient and reliable shearing of chromatin for highthroughput analysis, from 2019-03-28 to 2020-03-31