Brian Wilhelm’s research team uses the latest high-throughput technologies, such as next-generation DNA sequencing (e.g., RNA-seq, Cut-and-Run, ATAC-seq), and genome-wide CRISPR chemogenomic screens to elucidate the connections between transcriptional activity and the biology of pediatric leukemia.

Research theme

The ability to systematically sequence the entire genomes of cancer patients or to conduct high-resolution genome-wide association studies holds enormous potential for helping to elucidate the mechanisms underlying these diseases.

More specifically, Brian Wilhelm and his team use functional genomics approaches to study the genetic underpinnings of pediatric leukemia in order to understand how the disease arises and progresses.

The data generated by these approaches are then used to understand the basic mechanisms of transcriptional regulation, and in particular, dysregulation in the context of cancer. This new knowledge, combined with chemogenomic screening, aims to enable the development of new small-molecule-based therapies or immunotherapies for cancer.

Research objectives

Research conducted in Brian Wilhelm’s laboratory has led to the discovery of new genes that are consistently expressed in leukemic cells but not in normal blood cells. By further studying this small group of genes, the researchers are focusing their efforts on developing more effective treatments to improve survival rates for children with acute myeloid leukemia (AML).

Professor Wilhelm and his colleagues have also developed an in vivo experimental system capable of generating leukemias from umbilical cord blood samples using the same mutations found in patients. The sequencing and epigenetic data generated from these models help shed light on the molecular mechanisms underlying this disease.

In collaboration with the laboratories of Frédéric Barabé (Université Laval) and Sonia Cellot (Hôpital Saint-Justine), Brian Wilhelm and his team conducted large-scale pharmacological screens to identify new molecules capable of blocking the growth of leukemic cells while preserving normal hematopoietic stem cells. Many of these new molecules are currently undergoing characterization studies aimed at understanding their mechanism of action and validating their potential as targeted therapies.