Research Discipline(s): Basic, Translational
Primary Title: Professor, Department of Pharmacology and Therapeutics, University of Manitoba
Additional Titles & Affiliations: Senior Scientist, CCMR Head of Cancer Modeling and Imaging Core (CMIC), CCMR Professor, Department of Biochemistry &Medical Genetics, and Professor, Department of Immunology, University of Manitoba (Nil cross-appointments)
RESEARCH TOPICS
Transcriptional and epigenetic control of blood cancer with a focus on acute myeloid and acute lymphoid leukemia (AML, ALL).
Research Summary
Our group is interested in the role that misexpression of ZEB and SNAI transcription factors has on blood cell development and function that ultimately drives leukemic transformation. These EMT transcription factors (EMT-TFs) have previously been shown to play important role in tumor metastasis (ability of tumour cells to spread throughout the body), and the acquisition of cancer stem cell properties that drive resistance to chemotherapy and are involved in tumour relapse. We use conditional Cre/loxP dependent gain and loss of function mouse models, CRISPR/CAS9 based gene-editing technologies, leukemic cell lines, primary patient leukemic cells in xenograft settings and RNA sequencing approaches (RNAseq, single cell RNAseq) to identify and validate novel druggable targets and combination therapies that can be used to fight aggressive forms of blood cancers. We are particularly interested in epigenetic based therapies as a means of interfering with the transcriptional programs regulated by these EMT-TFs. In addition, our group has a long-standing interest in cell plasticity, and it pertains to differentiation-based therapies in cancers and in regeneration-based approaches within the blood system and beyond.
Goals
Our goals are to find and validate novel drug targets and drug combination approaches using relevant pre-clinical in vivo models that will eventually be used in clinical trials to fight aggressive forms of leukemia. We are particularly interested in epigenetic therapies that can specifically target leukemic stem cells (LSCs) that are responsible for relapse to standard of care chemotherapeutics.
Research Biography
I am a full professor in the Department of Pharmacology and Therapeutics at the University of Manitoba, Senior Scientist at the Paul Albrechtsen Research Institute, and leader of the Cancer Modelling and Imaging Core. I completed my undergraduate degree in Life Sciences and M.Sc. degree in Biochemistry at Queen’s University in Kingston, Canada. This was followed by a PhD in Biochemistry at the IMP/University of Vienna, Austria. I spent four years as a postdoctoral fellow in the lab of Dr. Andras Nagy at the Lunenfeld-Tanenbaum Research Institute at Mount Sinai hospital in Toronto. From 2004-2013 I was an assistant professor at Ghent University in Belgium and ran my own research group at the VIB. I was then recruited to the Australian Centre for Blood Diseases (ACBD) at Monash University in Melbourne, Australia on a Larkin’s Fellowship as an associate professor (2013-2018).
Throughout my career, my lab has developed and used novel mouse embryonic stem (ES) cell-based transgenic technologies to study genes involved in cardiovascular and hematopoietic development and disease related processes. I have co-authored numerous publications on the role of vascular endothelial growth factor (VEGF) signaling in organogenesis and disease processes including cancer.
Over the last several years my group has performed pioneering work on understanding the role that the epithelial to mesenchymal transition (EMT) transcriptional modulators of the ZEB and SNAI family play in blood development and leukemia and leukemic stem cells. I have had a long-standing interest in the molecular basis of cellular (de) differentiation, cellular reprogramming, and cellular memory and how these processes can be co-opted during cancer.
Achievements
- Larkins Fellowship – Monash University, Melbourne Australia (2013-2015)
- Tier II Canada Research Chair in Regenerative Medicine (Declined) (2011-2016)
- Terry Fox National Cancer Institute of Canada (NCIC) Postdoctoral Fellowship (2001-2004)
- Vienna Biocentre International PhD Studentship (1995-1999)
- Queen’s Graduate Award (1994-1995)
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Featured Publications
- EMT transcription factors in hematopoiesis and leukemic transformationJAK/BCL2 inhibition acts synergistically with LSD1 inhibitors to selectively target ETP-ALL
- The EMT transcription factor Zeb1 is essential for HSPC differentiation that acts synergistically with Zeb2 in fine-tuning hematopoietic lineage fidelity.
- The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1.
- ZEB2 and LMO2 drive immature T-cell lymphoblastic leukemia via distinct oncogenic mechanisms. ncogenic ZEB2 activation drives sensitivity towards LSD1 inhibition in T-cell acute lymphoblastic leukemia.
- Oncogenic ZEB2 activation drives sensitivity towards LSD1 inhibition in T-cell acute lymphoblastic leukemia.
- ZEB2 drives immature T-cell lymphoblastic leukemia development via altered IL-7 receptor signalling and enhanced tumor-initiating potential.
- Reversible reprogramming of cardiomyocytes to a fetal state drives adult heart regeneration in mice.
- The ROSA26-iPSC mouse: a conditional, inducible, and exchangeable resource for studying cellular (De)differentiation.
Publications List
Haigh Lab, Summer 2023
L to R, Tyler Anderson, Dr. Andrew Cuddihy, Prof. Jody J. Haigh, Katharina Haigh, Yazdan Rahmati, Kenneth Osafile, Michelle Fruehauf, Tapan Prajapati
Our Team
Jody Jonathan Haigh, PhD
Principal Investigator
Kenneth Osafile
M.Sc. Candidate
Katharina Haigh
Lab Manager
Yazdan Rahmati
M.Sc. Candidate
Tapan Prajapati
Summer Student
Dr. Andrew Cuddihy
Research Associate
Michelle Fruehauf
Summer Student
Tyler Anderson
M.Sc. Candidate
