My laboratory pioneered the modeling of blood cancers with human induced pluripotent stem cells (iPSCs). By reprogramming cells from patients with myeloid malignancies, such as Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), and by correcting and introducing mutations using CRISPR/Cas9-mediated gene editing, we are developing new models of leukemia and pre-leukemic blood disorders to study their mechanisms and identify new therapeutic targets.
My research program combines techniques and principles from stem cell research, cancer biology and hematopoiesis. The unifying theme of my lab’s projects is the creation of genetically precise iPSC disease models of myeloid cancers and exploitation of the unique capabilities they offer: the ability to perform genotype-to-phenotype studies to understand the effects of oncogenic mutations in a faithful cellular and genomic environment; the opportunity to explore the phenotypic and functional heterogeneity relevant to the cancer stem cell model emerging from genetic clones; the capability to obtain relatively homogeneous cell populations in large numbers for genetic and small molecule screens, including drug repurposing and drug discovery screens, and integrative genomics; and, finally, the ability to validate findings through functional assays with isogenic controls.
Our research sets the stage for wider adoption of patient-derived iPSCs as models of cancer at a time of a wider shift of the cancer research enterprise towards human-based models, such as patient-derived xenografts and tissue organoids.