I focus on hematopoietic stem cell transplantation (HSC) which is the only curative therapy for over 30 illnesses. However, HSCs are rare and the molecular mechanisms that govern HSC cell fate decisions are not well characterized. The overarching goal of our laboratory is to discover novel molecular programs/bioengineering technologies that lay the foundation for the development of new HSC products for cellular therapy. We use unbiased systems biology and integrative approaches to build gene-regulatory networks (GRNs) using omics (bulk-RNA-seq, ATAC-seq, ChIP-seq, single-cell RNA-seq) data we have generated in house. The GRNs are subsequently tested using reductionist approaches using CRISPR-Cas9 genome engineering technology to identify “drivers” of HSC fate.
The current projects in our laboratory are:
Project 1: Epi-transcriptomic regulation of hematopoietic stem and progenitor cells (HSPCs)
m6A and m6Am methylation are reversible epigenetic marks that control the stability of mRNA within all eukaryotes. While both m6A/m6Am levels have been previously implicated in leukemias, how they control human HSPC fate during homeostasis is not well understood. The goal of this project is to
- To elucidate new pathways to promote HSC expansion
- To identify the differential pathways controlled by m6A/m6Am marks during homeostasis versus cancer, that could then be targeted for precision therapy.
Project 2: CRISPR-Cas9 gene-editing of HSCs for treatment of Sickle Cell Disease (SCD)
Patients with SCD carry a mutation in the β-globin genes that impacts the functioning of red blood cells thereby depriving oxygen to vital organs within their body. In collaboration with the National Research Council of Canada, we are currently developing a novel platform that will enable us to correct the mutations within the HSCs isolated from patients with SCD and transplant them back into the patients.