My project was to target the lysosomal pathway to revert chemoresistance in AML cells with high expression of inositol polyphosphate 4-phosphatase type II (INPP4B). This includes building different cell models with overexpression and knock-down of INPP4B and evaluate their sensitivity towards chemotherapy in combination with lysosome inhibitors.I was also working on elucidating the relationship between INPP4B, ER stress signaling and stemness maintenance in AML.

My main project was studying the role of mtDNA mutation in leukemogenesis. While severe loss of mitochondrial function is detrimental to cells, it has been pointed out that mild mitochondrial dysfunction could provide cells with oncogenic or metastatic potential, creating a permissive metabolic zone. Using a recently developed gRNA-free genome editing tool, DddA-derived cytosine base editors, I was able to edit mt-Nd5 gene in mouse HSPCs. I also built standards to estimate single-cell heteroplasmy through qPCR.In addition, I have also contributed to other projects including: optimizing a Cas13-assisted tagging of live cells system; generating an immortalized murine HSPC line with tamoxifen-inducible Dnmt3a-knockout; studying the effect of drug combinations on clonal evolution of IDH-mutated cells with patient-derived xenograft models.

The main projects were focusing on examining the anti-tumor effects of the tested drugs using various mouse models. We also did repeated-dose toxicity study of the tested drugs in rats.