Charles De Smet

Major achievements

• Discovery of the “Cancer-germline“ genes: a group of spermatogenic genes that become aberrantly activated in wide variety of human tumors
• Demonstration of the primary role of DNA methylation in controlling the tissue-restricted expression of cancer-germline genes
• Identification of the transcriptional impacts of DNA hypomethylation in cancer

Question

• Which mechanisms cause epigenetic alterations in tumor cells, how do they spread across the genome?
• When do these epigenetic alterations appear during tumor development, can they serve as an early biomarker of disease ?
• Do genes activated by epigenetic alterations in tumors have a role in disease development ?

Research focus

Maintenance of gene expression programs is essential to ensure proper functioning of the various cell types that make up the body. To this end, cells have evolved “epigenetic“ regulatory mechanisms, based on the addition of chemical modifications on certain genes. Among these, DNA methylation serves to inactivate certain genes.

In many cancers, the distribution of DNA methylation marks is profoundly altered, and there is evidence that this contributes to tumor progression. The causes and consequences of this epigenetic disruption remain however unclear.

Charles De Smet and his group discovered that alterations of DNA methylation often affect a particular group of genes, which normally display specific expression in germline cells (especially those at the origin spermatozoids in males). These genes loose methylation in many tumors, and become therefore aberrantly activated. Due to their particular expression profile, such genes were termed “cancer-germline” (CG).

Current studies in the lab aim at identifying the mechanisms that lead to loss of methylation and activation of CG genes in tumors. Further efforts are focused on the identification of genes other than CG genes that also undergo epigenetic activation in cancer. To these ends, researchers in the team rely largely on bioinformatics approaches, which allow large-scale analysis of genomes and epigenomes.

Through the identification of epigenetically altered genes, the objective is to uncover new mechanisms of tumor development. Another goal is to search for early biomarkers of the disease.

Charles De Smet obtained his Master’s degree in Biology from the Catholic University of Louvain (Belgium) in 1987. He then joined the lab of Thierry Boon at the Brussels branch of the Ludwig Cancer Institute (Belgium), where he obtained his PhD in Molecular Biology in 1993 working on the isolation and characterization of genes that encode human tumor antigen. The genes turned out to be the first examples of cancer-germline genes. Charles stayed in the same lab as a postdoctoral fellow for 5 years, investigating the role of DNA methylation in the regulation of cancer-germline genes. He then continued his postdoctoral training in the group of Prof. Webster Cavenee at the University of California San Diego (USA), where he studied gene expression changes associated with differentiation of glial progenitor cells. Back in Belgium in 2000, Charles was hired as an Assistant Member at the Ludwig Cancer Institute. He joined the de Duve Institute as a Group Leader in 2008, and became Professor at UCLouvain in 2009. In 2021, Charles was elected President of the School of Biomedical Sciences of UCLouvain.

Honors

Affiliations

• Group Leader, de Duve Institute
• Full Professor, UCLouvain