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Jody Haigh

University of Manitoba, Pharmacology and Therapeutics, Faculty Member

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Dr. Jody Haigh is a full tenured Professor in the Department of Pharmacology and Therapeutics at the University of Manitoba and acting co-director of the CancerCare Manitoba Research Insitute. He completed his undergraduate degree in life sciences and Master of Science degree in Biochemistry at Queen’s University. This was followed by a PhD in Biochemistry at the IMP/University of Vienna, Austria. He 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 he was an Assistant Professor at Ghent University in Belgium and ran his own research group at the VIB. Dr. Haigh 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. In July 2018, he returned home to Canada in the Department of Pharmacology & Therapeutics and has re-established his research group at the CancerCare Manitoba Research Institute.
Throughout his career, he 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. He has 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 his group has started to 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. He has had a long-standing interest in the molecular basis of cellular (de) differentiation, cellular reprogramming, and cellular memory.
He has co-authored over 100 research articles in journals such as Blood, Cell Reports, Nature, Science Nature Medicine, Nature Cell Biology, and Nature Communications.
His publications have been cited more than 8,700 times.
Phone: 2047872134
Address: 675 McDermot Ave, ON5029 Winnipeg, MB Canada, R3E 0V9

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Papers by Jody Haigh

LIN28B is over-expressed in specific subtypes of pediatric leukemia and regulates lncRNA H19

Haematologica, Mar 11, 2016

Oncogenic ZEB2 activation drives sensitivity toward KDM1A inhibition in T-cell acute lymphoblastic leukemia

Blood, Feb 23, 2017

Opposing Roles for<i>Hoxa2</i>and<i>Hoxb2</i>in Hindbrain Oligodendrocyte Patterning

The Journal of Neuroscience, Nov 28, 2012

Neuronal FLT1 receptor and its selective ligand VEGF‐B protect against retrograde degeneration of sensory neurons

The FASEB Journal, Jan 19, 2011

AIF-regulated oxidative phosphorylation supports lung cancer development

Cell Research, May 27, 2019

VEGF-independent cell-autonomous functions of HIF-1α regulating oxygen consumption in fetal cartilage are critical for chondrocyte survival

Journal of Bone and Mineral Research, Feb 21, 2012

VEGF Mediates Commissural Axon Chemoattraction through Its Receptor Flk1

Neuron, Jun 1, 2011

Conditional inactivation of VEGF-A in areas of collagen2a1 expression results in embryonic lethality in the heterozygous state

Development, Apr 1, 2000

Autophagy inhibition by TSSC4 (tumor suppressing subtransferable candidate 4) contributes to sustainable cancer cell growth

Autophagy, Sep 17, 2021

Cancer cell growth is dependent upon the sustainability of proliferative signaling and resisting ... more Cancer cell growth is dependent upon the sustainability of proliferative signaling and resisting cell death. Macroautophagy/autophagy promotes cancer cell growth by providing nutrients to cells and preventing cell death. This is in contrast to autophagy promoting cell death under some conditions. The mechanism regulating autophagy-mediated cancer cell growth remains unclear. Herein, we demonstrate that TSSC4 (tumor suppressing subtransferable candidate 4) is a novel tumor suppressor that suppresses cancer cell growth and tumor growth and prevents cell death induction during excessive growth by inhibiting autophagy. The oncogenic proteins ERBB2 (erb-b2 receptor tyrosine kinase 2) and the activation EGFR mutant (EGFRvIII, epidermal growth factor receptor variant III) promote cell growth and TSSC4 expression in breast cancer and glioblastoma multiforme (GBM) cells, respectively. In EGFRvIII-expressing GBM cells, TSSC4 knockout shifted the function of autophagy from a pro-cell survival role to a pro-cell death role during prolonged cell growth. Furthermore, the interaction of TSSC4 with MAP1LC3/LC3 (microtubule associated protein 1 light chain 3) via its conserved LC3-interacting region (LIR) contributes to its inhibition of autophagy. Finally, TSSC4 suppresses tumorsphere formation and tumor growth by inhibiting autophagy and maintaining cell survival in tumorspheres. Taken together, sustainable cancer cell growth can be achieved by autophagy inhibition via TSSC4 expression.ABBREVIATIONS: 3-MA: 3-methyladenine; ACTB: actin beta; CQ: chloroquine; EGFRvIII: epidermal growth factor receptor variant III; ERBB2: erb-b2 receptor tyrosine kinase 2; GBM: glioblastoma multiforme; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule Associated protein 1 light chain 3; TSSC4: tumor suppressing subtransferable candidate 4.

Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline induction

Nucleic Acids Research, Mar 8, 2005

Supplementary Information from PTP1B Deficiency Enables the Ability of a High-Fat Diet to Drive the Invasive Character of PTEN-Deficient Prostate Cancers

Supplementary Materials and Methods, Supplementary Tables 1 and 2 and Supplementary Figures 1 through 5 from PTP1B Deficiency Enables the Ability of a High-Fat Diet to Drive the Invasive Character of PTEN-Deficient Prostate Cancers

Supplementary Materials and Methods. Table S1: List of the different oligonucleotides used for mo... more Supplementary Materials and Methods. Table S1: List of the different oligonucleotides used for mouse genotyping. Table S2: Phenotypic evaluation of prostate-specific PTP1B-overexpressing mice. Figure S1: Ptpn1 status does not alter the transition to mPIN in PtenPE-/- mice. Figure S2: Examples of mild and moderate desmoplasia. Figure S3: HFD drives invasive prostate cancer in the AP only in absence of Ptpn1. Figure S4: Ptpn1 status does not modulate mPIN formation in PtenPE+/- mice. Figure S5: Ptpn1 status influences PtenPE-/- phenotype in a dose-dependent manner.

Data from The EMT Transcription Factor ZEB2 Promotes Proliferation of Primary and Metastatic Melanoma While Suppressing an Invasive, Mesenchymal-Like Phenotype

Epithelial-to-mesenchymal transition (EMT)-inducing transcription factors (TF) are well known for... more Epithelial-to-mesenchymal transition (EMT)-inducing transcription factors (TF) are well known for their ability to induce mesenchymal states associated with increased migratory and invasive properties. Unexpectedly, nuclear expression of the EMT-TF ZEB2 in human primary melanoma has been shown to correlate with reduced invasion. We report here that ZEB2 is required for outgrowth for primary melanomas and metastases at secondary sites. Ablation of Zeb2 hampered outgrowth of primary melanomas in vivo, whereas ectopic expression enhanced proliferation and growth at both primary and secondary sites. Gain of Zeb2 expression in pulmonary-residing melanoma cells promoted the development of macroscopic lesions. In vivo fate mapping made clear that melanoma cells undergo a conversion in state where ZEB2 expression is replaced by ZEB1 expression associated with gain of an invasive phenotype. These findings suggest that reversible switching of the ZEB2/ZEB1 ratio enhances melanoma metastatic dissemination.Significance:ZEB2 function exerts opposing behaviors in melanoma by promoting proliferation and expansion and conversely inhibiting invasiveness, which could be of future clinical relevance.

Data from PTP1B Deficiency Enables the Ability of a High-Fat Diet to Drive the Invasive Character of PTEN-Deficient Prostate Cancers

Diet affects the risk and progression of prostate cancer, but the interplay between diet and gene... more Diet affects the risk and progression of prostate cancer, but the interplay between diet and genetic alterations in this disease is not understood. Here we present genetic evidence in the mouse showing that prostate cancer progression driven by loss of the tumor suppressor Pten is mainly unresponsive to a high-fat diet (HFD), but that coordinate loss of the protein tyrosine phosphatase Ptpn1 (encoding PTP1B) enables a highly invasive disease. Prostate cancer in Pten−/−Ptpn1−/− mice was characterized by increased cell proliferation and Akt activation, interpreted to reflect a heightened sensitivity to IGF-1 stimulation upon HFD feeding. Prostate-specific overexpression of PTP1B was not sufficient to initiate prostate cancer, arguing that it acted as a diet-dependent modifier of prostate cancer development in Pten−/− mice. Our findings offer a preclinical rationale to investigate the anticancer effects of PTP1B inhibitors currently being studied clinically for diabetes treatment as a new modality for management of prostate cancer. Cancer Res; 76(11); 3130–5. ©2016 AACR.

Oncogenic ZEB2 Activation Drives Sensitivity Towards LSD1 Inhibition in T-Cell Acute Lymphoblastic Leukemia

Blood, Dec 2, 2016

Dysregulation of Grainyhead-like 3 expression causes widespread developmental defects

Research Square (Research Square), Sep 16, 2021

TINC - a method to dissect transcriptional complexes at single locus resolution - reveals novel Nanog regulators in mouse embryonic stem cells

bioRxiv (Cold Spring Harbor Laboratory), Apr 4, 2020

The EMT regulator Zeb2 is essential for adult hematopoietic stem and progenitor cell differentiation

The role of VEGF-A in glomerular angiogenesis

Aberrant bone formation in mice over-expressing specific VEGF isoforms in cartilage

Journal of Bone and Mineral Research, Sep 1, 2005

LIN28B is over-expressed in specific subtypes of pediatric leukemia and regulates lncRNA H19

Haematologica, Mar 11, 2016

Oncogenic ZEB2 activation drives sensitivity toward KDM1A inhibition in T-cell acute lymphoblastic leukemia

Blood, Feb 23, 2017

Opposing Roles for<i>Hoxa2</i>and<i>Hoxb2</i>in Hindbrain Oligodendrocyte Patterning

The Journal of Neuroscience, Nov 28, 2012

Neuronal FLT1 receptor and its selective ligand VEGF‐B protect against retrograde degeneration of sensory neurons

The FASEB Journal, Jan 19, 2011

AIF-regulated oxidative phosphorylation supports lung cancer development

Cell Research, May 27, 2019

VEGF-independent cell-autonomous functions of HIF-1α regulating oxygen consumption in fetal cartilage are critical for chondrocyte survival

Journal of Bone and Mineral Research, Feb 21, 2012

VEGF Mediates Commissural Axon Chemoattraction through Its Receptor Flk1

Neuron, Jun 1, 2011

Conditional inactivation of VEGF-A in areas of collagen2a1 expression results in embryonic lethality in the heterozygous state

Development, Apr 1, 2000

Autophagy inhibition by TSSC4 (tumor suppressing subtransferable candidate 4) contributes to sustainable cancer cell growth

Autophagy, Sep 17, 2021

Cancer cell growth is dependent upon the sustainability of proliferative signaling and resisting ... more Cancer cell growth is dependent upon the sustainability of proliferative signaling and resisting cell death. Macroautophagy/autophagy promotes cancer cell growth by providing nutrients to cells and preventing cell death. This is in contrast to autophagy promoting cell death under some conditions. The mechanism regulating autophagy-mediated cancer cell growth remains unclear. Herein, we demonstrate that TSSC4 (tumor suppressing subtransferable candidate 4) is a novel tumor suppressor that suppresses cancer cell growth and tumor growth and prevents cell death induction during excessive growth by inhibiting autophagy. The oncogenic proteins ERBB2 (erb-b2 receptor tyrosine kinase 2) and the activation EGFR mutant (EGFRvIII, epidermal growth factor receptor variant III) promote cell growth and TSSC4 expression in breast cancer and glioblastoma multiforme (GBM) cells, respectively. In EGFRvIII-expressing GBM cells, TSSC4 knockout shifted the function of autophagy from a pro-cell survival role to a pro-cell death role during prolonged cell growth. Furthermore, the interaction of TSSC4 with MAP1LC3/LC3 (microtubule associated protein 1 light chain 3) via its conserved LC3-interacting region (LIR) contributes to its inhibition of autophagy. Finally, TSSC4 suppresses tumorsphere formation and tumor growth by inhibiting autophagy and maintaining cell survival in tumorspheres. Taken together, sustainable cancer cell growth can be achieved by autophagy inhibition via TSSC4 expression.ABBREVIATIONS: 3-MA: 3-methyladenine; ACTB: actin beta; CQ: chloroquine; EGFRvIII: epidermal growth factor receptor variant III; ERBB2: erb-b2 receptor tyrosine kinase 2; GBM: glioblastoma multiforme; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule Associated protein 1 light chain 3; TSSC4: tumor suppressing subtransferable candidate 4.

Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline induction

Nucleic Acids Research, Mar 8, 2005

Supplementary Information from PTP1B Deficiency Enables the Ability of a High-Fat Diet to Drive the Invasive Character of PTEN-Deficient Prostate Cancers

Supplementary Materials and Methods, Supplementary Tables 1 and 2 and Supplementary Figures 1 through 5 from PTP1B Deficiency Enables the Ability of a High-Fat Diet to Drive the Invasive Character of PTEN-Deficient Prostate Cancers

Supplementary Materials and Methods. Table S1: List of the different oligonucleotides used for mo... more Supplementary Materials and Methods. Table S1: List of the different oligonucleotides used for mouse genotyping. Table S2: Phenotypic evaluation of prostate-specific PTP1B-overexpressing mice. Figure S1: Ptpn1 status does not alter the transition to mPIN in PtenPE-/- mice. Figure S2: Examples of mild and moderate desmoplasia. Figure S3: HFD drives invasive prostate cancer in the AP only in absence of Ptpn1. Figure S4: Ptpn1 status does not modulate mPIN formation in PtenPE+/- mice. Figure S5: Ptpn1 status influences PtenPE-/- phenotype in a dose-dependent manner.

Data from The EMT Transcription Factor ZEB2 Promotes Proliferation of Primary and Metastatic Melanoma While Suppressing an Invasive, Mesenchymal-Like Phenotype

Epithelial-to-mesenchymal transition (EMT)-inducing transcription factors (TF) are well known for... more Epithelial-to-mesenchymal transition (EMT)-inducing transcription factors (TF) are well known for their ability to induce mesenchymal states associated with increased migratory and invasive properties. Unexpectedly, nuclear expression of the EMT-TF ZEB2 in human primary melanoma has been shown to correlate with reduced invasion. We report here that ZEB2 is required for outgrowth for primary melanomas and metastases at secondary sites. Ablation of Zeb2 hampered outgrowth of primary melanomas in vivo, whereas ectopic expression enhanced proliferation and growth at both primary and secondary sites. Gain of Zeb2 expression in pulmonary-residing melanoma cells promoted the development of macroscopic lesions. In vivo fate mapping made clear that melanoma cells undergo a conversion in state where ZEB2 expression is replaced by ZEB1 expression associated with gain of an invasive phenotype. These findings suggest that reversible switching of the ZEB2/ZEB1 ratio enhances melanoma metastatic dissemination.Significance:ZEB2 function exerts opposing behaviors in melanoma by promoting proliferation and expansion and conversely inhibiting invasiveness, which could be of future clinical relevance.

Data from PTP1B Deficiency Enables the Ability of a High-Fat Diet to Drive the Invasive Character of PTEN-Deficient Prostate Cancers

Diet affects the risk and progression of prostate cancer, but the interplay between diet and gene... more Diet affects the risk and progression of prostate cancer, but the interplay between diet and genetic alterations in this disease is not understood. Here we present genetic evidence in the mouse showing that prostate cancer progression driven by loss of the tumor suppressor Pten is mainly unresponsive to a high-fat diet (HFD), but that coordinate loss of the protein tyrosine phosphatase Ptpn1 (encoding PTP1B) enables a highly invasive disease. Prostate cancer in Pten−/−Ptpn1−/− mice was characterized by increased cell proliferation and Akt activation, interpreted to reflect a heightened sensitivity to IGF-1 stimulation upon HFD feeding. Prostate-specific overexpression of PTP1B was not sufficient to initiate prostate cancer, arguing that it acted as a diet-dependent modifier of prostate cancer development in Pten−/− mice. Our findings offer a preclinical rationale to investigate the anticancer effects of PTP1B inhibitors currently being studied clinically for diabetes treatment as a new modality for management of prostate cancer. Cancer Res; 76(11); 3130–5. ©2016 AACR.

Oncogenic ZEB2 Activation Drives Sensitivity Towards LSD1 Inhibition in T-Cell Acute Lymphoblastic Leukemia

Blood, Dec 2, 2016

Dysregulation of Grainyhead-like 3 expression causes widespread developmental defects

Research Square (Research Square), Sep 16, 2021

TINC - a method to dissect transcriptional complexes at single locus resolution - reveals novel Nanog regulators in mouse embryonic stem cells

bioRxiv (Cold Spring Harbor Laboratory), Apr 4, 2020

The EMT regulator Zeb2 is essential for adult hematopoietic stem and progenitor cell differentiation

The role of VEGF-A in glomerular angiogenesis

Aberrant bone formation in mice over-expressing specific VEGF isoforms in cartilage

Journal of Bone and Mineral Research, Sep 1, 2005