This week we profile a recent publication in Nature Communications
from Dr. Aly Karsan (back left) at the BC Cancer Agency.
Can you provide a brief overview of your lab’s current research focus?
My lab is currently interested in two areas in understanding the molecular basis and vulnerabilities of myeloid malignancy, neither of which is easily addressed by sequencing the genome. The first is in understanding how noncoding RNAs regulate the transcriptome and proteome, where we are interested in further understanding the post-transcriptional modifications of miRNAs, and also how other small noncoding RNAs regulate cell function. The second area of interest is in understanding how the ubiquitin-proteasome system regulates the proteome in AML.
What is the significance of the findings in this publication?
In this publication we explore how two miRNAs that are always deleted in a type of myelodysplastic syndrome (MDS, a marrow failure/leukemia syndrome) regulate blood stem cells and progenitor cells differentially. Our findings suggest that these two miRNAs, miR-143 and miR-145, regulate the TGF-beta signaling pathway through a protein called DAB2. When these miRNAs are lost in MDS, activation of the TGF-beta pathway depletes blood stem cells but expands the progenitor cell population, which eventually leads to leukemia in some cases. These findings help explain how sometime MDS can lead to acute leukemia.
What are the next steps for this research?
The next steps in this research is to understand whether we can target the miRNAs that lead to leukemia. Because these miRNAs are depleted in MDS, we are looking to see which of the mRNAs targeted by miR-143 and miR-145 can be inhibited in order to exploit a leukemic cell dependency.
This research was funded by:
TFRI, CIHR, Cancer Research Society, Leukemia Lymphoma Society of Canada, Genome BC, Genome Canada, BC Cancer Foundation
