Kate Graham

Supervisor:

Dr. Eric Allain

Co-Supervisor:

Dr. Luc Boudreau

Program of Study:

MSc, Biochemistry

Project Title:

Characterizing cis-acting lncRNAs that regulate lipid- metabolism enzymes in megakaryoblasts

Lay Research Summary:

Megakaryocytes are known for their role in platelet generation. During this process, megakaryocytes transfer their bioactive contents into newly formed platelets. This includes inflammatory enzymes such as 12-lipoxygenase (12-LO), a key protein in the pro-inflammatory response. Dysregulation of 12-LO can contribute to several pathologies, including cancer. Although 12-LO is expressed in mature human megakaryocytes, we have discovered two cell lines of megakaryoblasts (MEG-01 and DAMI) isolated from patients diagnosed with leukemia, where only DAMIs express 12-LO after differentiation. This suggests that the expression of 12-LO can be selectively activated and hints at possible heterogeneity in expression patterns within myeloid leukemias. We have identified a long non-coding RNA (lncRNA) ALOX12-AS1 in MEG-01 cells that has been shown to repress 12-LO. Therefore, our hypothesis is that cis-acting lncRNAs regulate the expression of genes critical to lipid metabolism and immune function in cancer. Our goal is to sequence RNA from megakaryocytes at different stages of differentiation using third-generation sequencing technologies to map the transcriptome dynamics of lipid-metabolizing enzymes.

Location:

Université de Moncton