RESEARCH PROJECTS
We are investigating the roles of RNA modifications as well as mechanisms of RNA splicing in normal biology and cancers. Our specific research interests are:
Elucidating the roles of RNA modifications and splicing during white blood cell differentiation
Identifying mechanisms of aberrant RNA splicing in cancers.
Determining the functional consequences of aberrant RNA modifications in cancers, including leukemia, breast and prostate cancers.
PROJECT 1
Determining the roles of intron retention in white blood cells and leukemia
In 2013, we reported intron retention as a mechanism that regulates gene expression during normal granulocyte differentiation (Wong et al Cell, 2013). Intron retaining mRNA transcripts may be prevented from being exported from the nucleus into the cytoplasm for protein translation, and are often degraded. In some cases, they may be translated into novel protein isoforms. We have since demonstrated that intron retention is regulated by epigenetic mechanisms (Wong et al Nature Communications, 2017) and are highly conserved in vertebrate species (Schmitz et al Genome Biology, 2017 ). We are now focusing on determining the roles of intron retention in the development of other white blood cells and leukemias.
PROJECT 2
Determining the roles of RNA modifications during white blood cell differentiation
Modifications to mRNAs including m6A, 5mC and 5hmC are now established as regulators of RNA processing, mRNA stability and protein translation, thereby affecting all biological processes. Our lab is interested in determining how these modifications to mRNAs control terminal differentiation of myeloid cells, including granulocytes and monocytes. We are also investigating the roles of m6A in controlling their functions in innate immune response.
PROJECT 3
Determining the roles aberrant RNA modifications in cancer
Aberrant expression of enzymes regulating RNA modifications is clearly implicated in diverse human cancers. We are currently exploring mechanisms underlying the abnormal expression of these enzymes in cancers. We are also determining mRNA transcripts that are affected by aberrant RNA modifications in cancers including leukemias, breast and prostate cancers.
