MCCB student Kelsey Wagner awarded grant to study mechanisms of disease relapse in childhood leukemia

Kelsey Wagner, a 5th year graduate student in the lab of Michelle Kelliher, PhD, has received an Emerging Scientist Grant from the private foundation Kids Beating Cancer.

Wagner’s thesis research focuses on elucidating the molecular mechanisms that drive therapy resistance and disease relapse in T-cell acute lymphoblastic leukemia (T-ALL), an aggressive form of leukemia that primarily affects children. Relapse is thought to arise from a rare subpopulation of cells known as leukemia-initiating cells (L-ICs), which are quiescent (dormant) and resistant to chemotherapy, but can later exit quiescence, begin proliferating and re-establish disease.

Recent work from the Kelliher lab identified a gene expression signature in T-ALL mouse-derived L-ICs, which revealed upregulation of Btg2, a gene encoding a protein known to regulate quiescence in T cells through its ability to promote mRNA deadenylation and decay.  Interestingly, BTG2 is downregulated in relapsed T-ALL patients, suggesting decreased BTG2 expression may contribute to disease progression.

In her Emerging Scientist Grant project, Wagner will use RNA-sequencing (RNA-seq) and poly-A tail length sequencing (PAL-seq, done in collaboration with Athma Pai’s lab in the RNA Therapeutics Institute) to comprehensively identify BTG2 target mRNAs. The goal of the research project is to generate a list of validated BTG2 targets that can be further evaluated in mouse xenograft experiments to determine whether their depletion resensitizes therapy-resistant T-ALL patient samples to chemotherapy—thereby uncovering potential targets for therapeutic development.