Associate Professor, Department of Pharmacology and Therapeutics
Senior Scientist, Research Institute in Oncology and Hematology
The Haigh lab is presently working on understanding the role that transcription factors of the ZEB (ZEB1,2) and SNAI (SNAI1-3) families play in both normal hematopoiesis and in leukemic transformation. The ZEB and SNAI family of transcription factors (TFs) are perhaps best known for their roles in regulating epithelial cell migration and epithelial to mesenchymal transition (EMT) that has been implicated and cancer cell metastasis, in the acquisition of tumour stemness properties, and in radiatiation and chemotherapy resistance. We have found novel roles for these EMT-TFs in regulating hematopoietic stem and progenitor cell (HSPC) differentiation and migration. In addition, we have also found roles of dyregulated ZEB2 and SNAI1 in leukemia development and progression. Overexpresion of ZEB2 has been found to be associated with the early transformation of T-cell progenitors and results in a diease that resembles early thymic progenitor acute lymphoblastic leukemia (ETP-ALL). As well, overexpression of ZEB1/2 as well as SNAI1 has been implication in acute myeloid leukemia (AML) development and progression. We believe that the ability of ZEB and SNAI EMT-TF to drive leukemia development rests in their ability to alter key epigenetic modulators such as the Lysine Specific Demethylase 1 (LSD1/KDMA1) as well as key oncogenic transcriptional programs. We have previously demonstrated that ETP-ALL leukemic cells that have high ZEB2 expression are suceptible to inhibitors against LSD1. Our lab is presently further investigating direct and potentially druggable transcriptional targets as well as chromatin interacting partners of EMT-TF in leukemic contects using RNAseq and ChIPseq based approaches with the hopes of better understanding the role of EMT-TF is leukemic disease and in developing novel drug combination therapies that can be used in fight aggressive and refractory forms of leukemia.