Research Institute in Oncology and Hematology

Jody Haigh

Stem Cells in Development and Disease

Jody Haigh Contact: Dr. Jody Jonathan Haigh Ph.D.

 

Associate Professor

Department of Pharmacology and Therapeutics (Since August 2018)

Rady Faculty of Health Sciences

University of Manitoba

 

Senior Scientist

Research Institute in Oncology and Hematology (RIOH) (Since August 2018)

CancerCare Manitoba, ON5029

675 McDermot Ave

Winnipeg, MB

Canada, R3E 0V9

Tel: 204-787-2134 

Mob: 204-995-9042

E-mail: jody.haigh@umanitoba.ca

Stem Cells in Development and Disease

Overview

 

  Two major developments have occurred in the last decade or so that have changed our view of cellular plasticity and have revolutionized how we can attempt to alter cell fate and study gene function. The first is the Nobel Prize winning discovery by Takahashi and Yamanaka that it only takes four transcription factors (Oct-4, Sox2, KLF4, and c-Myc) to reprogram a differentiated cell (2006). These reprogrammed cells have come to be known as induced pluripotent stem (iPS) cells and are very similar if not identical to pluripotent embryonic stem (ES) cells that can give raise to any cell type in the body. The second discovery is the advent of the CRISPR/Cas9 system and Cas9 variants that have made altering gene function in vitro and in vivo much easier than ever before and has sparked a genome editing revolution.  We plan on using these technologies in concert with RNAseq and ChIPseq analysis to better understand the molecular underpinnings of both normal and cancer stem cell states.

  Throughout my career I have been extremely fortunate to have been trained and have worked at leading research institutions in Europe (IMP, VIB), Australia (ACBD, ARMI) and Canada (SLRI, and now RIOH/CancerCare Manitoba and Department of Pharmacology and Therapeutics, U of M).  My lab has developed novel mouse embryonic (ES) and induced pluripotent stem (iPS) cell-based technologies to study gene function in both normal physiological as well as pathological contexts. Previously, my group has used these technologies in collaboration with other leading experts in their respective fields to address the role of VEGF/VEGF-R signaling and the p53 tumour suppressor in hematopoiesis, neurobiology and cancer. In the last 5 years or so my group has shifted focus and begun to unravel the novel and unexpected role that the SNAI and ZEB family of transcription factors play in both normal hematopoiesis and leukemic transformation with a particular focus on the role of ZEB2 in aggressive forms of T-cell acute lymphoblastic leukemia (ETP-ALL) as well as the roles of ZEB proteins and SNAI1 in acute myeloid leukemia (AML).  Research funding is or will be sought in the following 3 areas:

 

Role of EMT transcription factors in hematopoietic and leukemic stem cell biology

 

  Our lab is studying the role of Snai1 and Zeb1/2 transcription factors in blood cell development (hematopoiesis) and blood cancers (leukemic transformation).  These transcription factors have previously been demonstrated to play important roles in epithelial to mesenchymal transition (EMT) events that are necessary for the spread of solid tumor cells to distinct sites in the body (metastasis). Increased expression of these EMT transcription factors (EMT-TFs) has also been associated with the acquisition of cancer stem cell properties that are the driving force behind resistance to drug/radiation therapy and cancer relapse.  Our group has previously demonstrated that these EMT-TFs also play important roles in normal blood cell development (Goossens et al., Blood 2011, Li et al, Blood 2017) and in their transformation (Goossens et al, Nature Communications, 2015).  We and others have demonstrated that ZEB and SNAI family protein levels have to be tightly regulated during normal hematopoietic development and if they become upregulated or mis-expressed can lead to blocks in hematopoietic differentiation and acquisition of self-renewal properties that allow these aberrant cells to accumulate additional mutations to become leukemic stem cells (LSCs).  These LSCs are responsible for giving rise to leukemic transformation, chemoresistance, and disease relapse.  One potential mechanism that may be involved is the alterations of key epigenetic modulators and transcriptional programs that may be the target of pharmacological intervention (Goossens et al., Blood 2017).  We plan on further investigating how these EMT-TFs control normal hematopoietic stem cells (HSCs) and can drive the development of leukemic stem cells when overexpressed in AML mouse models and using human AML primary samples and cell lines.  We aim to identify and functionally validate novel genetic and epigenetic targets of these EMT-TFs using CRISPR/Cas9 gain and loss of function-based strategies as well as combinatorial pharmacological approaches that can be used to terminally differentiate or kill leukemic stem cells. 

 

Role of VEGF signaling in cancer stem cell biology

 

My group has previously contributed significantly to the understanding of how Vascular Endothelial Growth Factor (VEGF) signalling can affect vascular patterning and function that impacts either directly or indirectly on organ structure and function.  One key aspect that has immerged is that of the strong functional link between stem cells and their vascular niche that is essential to maintain stemness properties.  This link is best understood in terms of neuronal and hematopoietic stem cells but there is emerging data that VEGF signaling plays essential autocrine as well as paracrine roles in regulating the Cancer Stem Cell Niche in certain solid tumour contexts (for example see Beck et al., Nature, 2011).  Using genetic gain/loss of function as well as pharmacological approaches we plan on investigating the role of VEGF signaling in both leukemic stem cells in established AML models as well as its role in brain cancer stem cell biology using newly established glioblastoma models in the mouse.

 

Development and use of novel ES/iPS and CRISPR/Cas9 models to understand cell lineage identity and transformation

 

With the advent of iPS technologies the ability to study disease causing mutations in human disease contexts in vitro has expanded rapidly.  This ‘disease in a dish’ approach offers new avenues for understanding the molecular underpinnings of disease-causing mutations and offers the opportunity to develop high throughput screening platforms for drug discovery and genome-wide screening applications using CRISPR/Cas9 technologies.  We plan on continuing our work in creating human iPS cells from primary AML and control blood cells for the purposes of understanding how major AML driver mutations are capable of causing defects in hematopoietic development and allow the cell to adopt a leukemic stem cell fate.  These AML-iPS platforms will complement our existing mouse AML models and will be used to validate the role of novel EMT-TF targets in human AML settings.

 

Previously our lab has developed very efficient Rosa26 locus targeting approaches for studying gene function in both a Cre/loxP cell-specific and drug-regulated temporal manner (Nyabi et al., NAR 2009, Haenebalcke et al., Stem Cell Rev, 2013).  These technologies have been used to develop a novel reprogramming mouse model that allows researchers to more easily study the process of cellular reprogramming and lineage directed differentiation (Haenebalcke et al., Cell Reports, 2013).  Using these technologies, we are presently developing novel cell-specific and temporally regulatable Cas9 mice with variants of Cas9 that will allow us to perform gain/loss of function studies in the mouse in a more efficient manner.  These mice will be used in the in vivo dissection of key determinants in cancer stem cell state in both AML and in brain cancer models.

 



Team Members

  •     Jody Haigh, Ph.D.-Principle Investigator
  •   Katharina Haigh-Lab Manager

     

    We are seeking very highly motivated graduate students and postdoctoral fellows (with a strong history of previous success) to join our team from January 2019 onwards.

Previous Positions:

 

Associate Professor, Mammalian Functional Genetics Lab, Primary Appointment-Australian Centre for Blood Diseases (ACBD) (2013-2018), Secondary Appointment-Australian Regenerative Medicine Institute (ARMI) (2015-2018), Monash University, Melbourne, Australia.

 

Group Leader (2004-2013) and Assistant Professor (2009-2014), Vascular Cell Biology Unit VIB/Ghent University, Ghent, Belgium

 

Training:

 

Postdoctoral Training (2000-2004) Samuel Lunenfeld Research Institute (SLRI), Mount Sinai Hospital, Lab of Professor Andras Nagy, Toronto, Ontario Canada

 

Ph.D. (1995-2000)-Research Institute of Molecular Pathology (IMP), Lab of Professor Erwin F. Wagner, University of Vienna, Vienna, Austria

 

M.Sc. (1992-1995)-Cancer Research Institute, Lab of Professor Peter A. Greer, Queen’s University, Kingston, Ontario, Canada

 

B.Sc.H (1988-1992)-S.Sp. Life Sciences, Queen’s University, Kingston, Ontario, Canada


Past Haigh Lab Research Trainees

 

Post-Doctoral Fellows

  • Dr. Omar Nyabi
  • Dr. Steven Goossens
  • Dr. Benjamin Drogat
  • Dr. Tim Pieters
  • Dr. Magdalene Costa
  • Dr. Catherine Carmichael
  • Dr. Jackie Wang

 

Research Assistants

  • Dr. Sonia Bartunkova,
  • Michael Naessens
  • Dr. Thao Nguyen
  • Katharina Haigh (present Lab Manager)

 

Graduate Students

  • Mina Takawy (Ph.D., pending)
  • Lieven Haenebalcke (M.Sc., Ph.D.)
  • Morvarid Farhang-Ghahremani (Ph.D.)
  • Johanna Kalucka (M.Sc.)
  • Karolina Slowicka (M.Sc.)
  • Pieterjan Dierickx (M.Sc.)
  • Sarah Corradi (M.Sc.)
  • Steven Cool (M.Sc.)
  • Katrien Verwaest (M.Sc.)
  • Bouchra Nouman (M.Sc.)
  • Joseph Reagan (M.Sc.)  
  • Mark Rogers (M.Sc.)

 

Undergraduate 4th Year Honours Thesis

  • Anna Milne (B.Sc.H.)
  • Max Garland (B.Sc. H.)
  • William McInnes (B.Sc.H.)
  • Adam Rickard (B.Sc. H.)

Publications Since 2010

(underlined names are past/present Haigh Lab members, *equal contribution ***Denotes top level publications, IF=Impact Factor, CIT >50 Citations)

 

For a full publication list see:

 

https://scholar.google.ca/citations?user=OJHQsdQAAAAJ&hl=en

 


2019


80.   AIF-regulated oxidative phosphorylation supports lung cancer development. Rao S, Mondragón L, Pranjic B, Hanada T, Stoll G, Köcher T, Zhang P, Jais A, Lercher A, Bergthaler A, Schramek D, Haigh K, Sica V, Leduc M, Modjtahedi N, Pai  TP, Onji M, Uribesalgo I, Hanada R, Kozieradzki I, Koglgruber R, Cronin SJ, She Z, Quehenberger F, Popper H, Kenner L, Haigh JJ, Kepp O, Rak M, Cai K, Kroemer G, Penninger JM.  Cell Res. 2019 May 27. doi: 10.1038/s41422-019-0181-4. [Epub ahead of print] PubMed PMID: 31133695. (IF=15.6)

79. Modulating PKCα Activity to Target Wnt/β-Catenin Signaling in Colon Cancer. Dupasquier S, Blache P, Picque Lasorsa L, Zhao H, Abraham JD, Haigh JJ, Ychou  M, Prévostel C. Cancers (Basel). 2019 May 18;11(5). pii: E693. doi: 10.3390/cancers11050693. PubMed PMID: 31109112. (IF=5.32)

78.  GNrep mouse: A reporter mouse for front-rear cell polarity. Barbacena P, Ouarné M, Haigh JJ, Vasconcelos FF, Pezzarossa A, Franco CA. Genesis. 2019 Apr 16:e23299. doi: 10.1002/dvg.23299. [Epub ahead of print] PubMed PMID: 30990965. (IF=2.16)

77. ZEB2 and LMO2 drive immature T-cell lymphoblastic leukemia via distinct oncogenic mechanisms. Goossens S, Wang J, Tremblay C, De Medts J, T'Sas S, Nguyen T, Saw J, Haigh K, Curtis DJ, Van Vlierberghe P, Berx G, Taghon T, Haigh JJ. Haematologica. 2019 Jan 24. pii: haematol.2018.207837. doi:10.3324/haematol.2018.207837. [Epub ahead of print] PubMed PMID: 30679322. (IF=9.09)


2018

 

76.  The pulmonary microvasculature entraps induced vascular progenitor cells (iVPCs) systemically delivered after cardiac ischemia-reperfusion injury: Indication for preservation of heart function via paracrine effects beyond engraftment. Ziegler M, Haigh K, Nguyen T, Wang X, Lim B, Yap ML, Eddy EM, Haigh JJ*, Peter K.*. *equal contributions

Microcirculation. 2018 Jul 21: e12493. (IF=2.79)

 

75.  Intravital Imaging to Monitor Therapeutic Response in Moving Hypoxic Regions Resistant to PI3K Pathway Targeting in Pancreatic Cancer. Conway JRW, Warren SC, Herrmann D, Murphy KJ, Cazet AS, Vennin C, Shearer RF, Killen MJ, Magenau A, Mélénec P, Pinese M, Nobis M, Zaratzian A, Boulghourjian A, Da Silva AM, Del Monte-Nieto G, Adam ASA, Harvey RP, Haigh JJ, Wang Y, Croucher DR, Sansom OJ, Pajic M, Caldon CE, Morton JP, Timpson P.

Cell Rep. 2018 Jun 12;23(11):3312-3326.  (IF=8.03)

 

74. Expressed repetitive elements are broadly applicable reference targets for normalization of reverse transcription-qPCR data in mice.  Renard M, Vanhauwaert S, Vanhomwegen M, Rihani A, Vandamme N, Goossens S, Berx G, Van Vlierberghe P, Haigh JJ, Decaesteker B, Van Laere J, Lambertz I, Speleman F, Vandesompele J, Willaert A.

Sci Rep. 2018 May 16;8(1):7642.  (IF=4.12)

 

***73. A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8.  Delphine Bouhy, Manisha Juneja, Istvan Katona, Anne Holmgren, Bob Asselbergh, Vicky De Winter, Tino Hochepied, Steven Goossens, Jody J. Haigh, Claude Libert, Chantal Ceuterick-de Groote, Joy Irobi, Joachim Weis, Vincent Timmerman

Acta Neuropathol. 2018 Jan;135(1):131-148. (IF=15.87)

 

2017

 

72. Platelet-Targeted Delivery of Peripheral Blood Mononuclear Cells to The Ischemic Heart Restores Cardiac Function After Ischemia-Reperfusion Injury. Melanie Ziegler, Xiaowei Wang, Bock Lim, Ephraem Leitner, Franco Klingberg, Victoria Ching, Yu Yao, Dexing Huang, Xiao-Ming Gao, Helen Kiriazis, Xiao-Jun Du, Jody J. Haigh, Alex Bobik, Christoph E. Hagemeyer, Ingo Ahrens, Karlheinz Peter

Theranostics. 2017 Jul 22;7(13):3192-3206. (IF=8.71)

 

71.  Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase-mediated Cassette Exchange.  Pieters, T., Haenebalcke, L., Bruneel, K., Vandamme, N., Hochepied, T., van Hengel, J., Wirth, D., Berx, G., Haigh, J. J., Van Roy, F., Goossens, S.

J Vis Exp. 2017 Apr 27;(122). (IF=1.24)

 

70. Zeb2 is essential for pluripotency exit and neural differentiation of mouse embryonic stem cells. Stryjewska, A., Dries, R., Pieters, T., Verstappen, G., Conidi, A., Coddens, K., Umans, L., van Ijcken, W., van Grunsven, L.A., Goossens, S., Haigh, J.J., Huylebroeck, D. 

Stem Cells, 2017, March. 35(3): 611-625 (IF=5.59)

 

***69. Oncogenic ZEB2 activation drives sensitivity towards LSD1 inhibition in T-cell acute lymphoblastic leukemia. Steven Goossens*, Sofie Peirs*, Wouter Van Loocke, Mina Takawy, Stefan Sonderegger, Katharina Haigh, Thao Nguyen, Niels Vandamme, Magdaline Costa, Catherine Carmichael, Filip Van Nieuwerburgh, Dieter Deforce, Oded Kleifeld, David Curtis, Geert Berx, Pieter Van Vlierberghe* and Jody J. Haigh*

Blood. 2017 Feb 23;129(8):981-990. (IF=15.13)

 

***68. Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10. Hammad H, Vanderkerken M, Pouliot P, Deswarte K, Toussaint W, Vergote K, Vandersarren L, Janssens S, Ramou I, Savvides SN, Haigh JJ, Hendriks R, Kopf M, Craessaerts K, de Strooper B, Kearney JF, Conrad DH, Lambrecht BN

Nature Immunology, 2017 Feb 15. 18(3): 313-320 (IF=21.81)

 

67. Elevated ΔNp63α levels facilitate epidermal and biliary oncogenic transformation. Devos, M., Gilbert, B., Denecker, G., Leurs, K., McGuire, C., Lemeire, K., Hochepied, T., Lambert, J., Van Den Broecke, C., Libbrecht, L., Haigh, J.J., Berx, G., Lippens, S., Vandenabeele, P., Declercq, W.

Journal of Investigative Dermatology, 2017, Feb 1. 137(2): 494-505 (IF=6.45)

 

66. The Snail family in normal and malignant hematopoiesis. Catherine Carmichael and Jody J. Haigh

Cells, Tissues, Organs (Review) 2017, Feb 1. 203(2): 82-98 (IF=0.98)

 

***65. The EMT transcription factor controls adult murine hematopoietic differentiation by regulating cytokine signaling. Li, J.*, Riedt, T.*, Goossens, S.*, García, C.C., Dobrosch, L., Gütgemann, I., Radaelli, E., Fröhlich, H., Huylebroeck, D., Brossart, P., Haigh, J.J., and Janzen V. 

Blood, 2017, Jan 26. 129(4): 460-472 (IF=15.13)

 

2016

 

64. p120 Catenin-Mediated Stabilization of E-cadherin is Essential for Primitive Endoderm Specification. Tim Pieters, Steven Goossens, Lieven Haenebalcke, Vanessa Andries, Agata Stryjewska, Riet Derycke, Kelly Lemaire, Tino Hochepied, Danny Huylebroeck, Geert Berx, Marc Stemmler, Dagmar Wirth, Jody J. Haigh, Frans Van Roy*, Jolanda Van Hengel*.

PLOS Genetics, 2016, Aug 24. 12(8):1-28 (IF=7.17)

 

63. Characterization of new transgenic mouse models for two Charcot-Marie-Tooth-causing HspB1 mutations using the Rosa26 locus. Delphine Bouhy, Thomas Geuens, Vicky De Winter, Leonardo De Almeida Souza, Istvan Katona, Joachim Weis, Tino Hochepied, Steven Goossens, Jody J. Haigh, Sophie Janssens, Vincent Timmerman 

Journal of Neuromuscular Diseases, 2016, May 27. 3(2): 183-200 (IF=NA)

 

***62. LIN28 is over-expressed in specific subtypes of pediatric leukemia and regulates lncRNA H19. Helsmoortel HH, De Moerloose B, Pieters T, Ghazavi F, Bresolin S, Cave' H, de Vries A, de Haas V, Flotho C, Labarque V, Niemeyer C, De Paepe P, Van Roy N, Stary J, van den Heuvel-Eibrink MM, Benoit Y, Schulte J, Goossens S, Berx G, Haigh JJ, Speleman F, Van Vlierberghe P, Lammens T. 

Haematologica (2016) Jun. 101(6):e240-4.  (IF=9.09)

 

***61. PTP1B deficiency enables the ability of a high fat diet to drive the invasive character of PTEN-deficient prostate cancers. Labbé, D.P., Uetani, N., Vinette, V., Aubry, I., Migon, E., Sirois, J., Haigh, J. J., Lessard, L., Bégin, L.R., Trotman, L.C., Paquet, M., Tremblay, M.L. (2016) 

Cancer Res Jun 1. 76 (11): 3130-5.  (IF=9.13)

 

***60. The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs. Charlotte Scott, Bieke Soen, Liesbet Martens, Nicolas Skrypek, Wouter Saelens, Joachim Taminau, Gillian Blancke, Gert Van Isterdael, Danny Huylebroeck, Jody J. Haigh, Yvan Saeys, Martin Guilliams, Bart Lambrecht, and Geert Berx. 

JEM (2016), May 30. 213(6): 897-911.  (IF-10.79)

 

2015

 

***59. Terminal NK cell maturation I controlled by concerted ctions of T-Bet and Zeb2 and is essential for melanoma rejection. Van Helden*, M., Goossens*, S., Daussy*, C., Debaud, A.L., Faure, F., Marçais, A., Vandamme, N., Mayol, K., Viel, S., Degouve, S., Debien, E., Seuntjens, E., Conidi, A., Chaix, J., Mangeot, P., de Bernard, S., Buffat, L., Haigh, J.J., Lambrecht, B., Huylebroeck, D., Berx, G., and Walzer T.  

JEM 2015 Nov 16; 212(12):2015-25. (IF-10.79)

 

***58. A role for transcriptional repressor ZEB2 in the differentiation of CD8+ effector and memory T cell populations. Omilusik, K.D., Best, J.A., Yu, B., Nguyen, J.V., Goossens, S., Seuntjens, E., Weidemann, A., Zweier, C., Bird, L., Kondoh, H., Huylebroeck, D., Haigh, J.J., Goldrath, A.W.

JEM 2015 Nov 16; 212(12):2027-39. (IF-10.79)

 

57. Novel biological insights in T-cell acute lymphoblastic leukemia. Durinck K, Goossens S, Peirs S, Wallaert A, Van Loocke W, Matthijssens F, Pieters T, Milani G, Lammens T, Rondou P, Van Roy N, De Moerloose B, Benoit Y, Haigh J, Speleman F, Poppe B, Van Vlierberghe P.

Exp Hematol 2015 Aug;43(8):625-39. (Review) (IF=2.44) (CIT=50)

 

56. Muller glia are a major cellular source of survival signals for retinal neurons in diabetes. Fu, S., Dong, S., Zhu, M., Sherry D.M., Wang, C., You, Z., Haigh, J.J., Le, Y.Z. 

Diabetes, 2015 Oct;64(10):3554-63. (IF=7.27)

 

55. Strategies to Rescue the Lethal Consequences of Inducible Arginase-1 Deficiency in Mice. Ballantyne, L. L., Yan Sin, Y., St. Amand, T., Si, J., Goossens, S., Haenebalcke, L., Haigh, J. J., Schulze, A., Funk, C.D.

PLOS One,10(5):e0125967 (2015) (IF=3.54)

 

***54. LOXL2 promotes squamous cell carcinoma progression and breast lung metastasis influencing the Notch pathway and bone marrow recruitment. Martin, A., Salvador, F., Floristán, A., Moreno-Bueno, G., Morales, S., Santos, V., Csiszar, K., Dubus, P., Haigh, J.J., Portillo, F., Cano A.  

EMBO J, 34(8):1090-109 (2015) (IF=9.79)

 

***53. Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium. Horvay, K., Jarde, T., Casagranda F., Perreau V.M., Haigh, K., Gridley, T., Berx, G., Haigh, J.J., Barker, N., Polo, J.M., Hime, G.R., Abud, H.E.  

EMBO J, 12;34(10):1319-35 (2015) (IF=9.79)

 

52. ER-directed gelsolin nanobody establishes therapeutic merit in the gelsolin amyloidosis mouse model by shielding mutant plasma gelsolin from furin proteolysis.

Van Overbeke, W., Wongsantichon, J., Everaert, I., Verhelle, A., Zwaenepoel, O., De Ganck, A., Hochepied, T., Haigh, J.J., Cuvelier, C., Derave, W., Robinson, R., Gettemans, J.

Hum Mol Genet 24(9):2492-507 (2015) (IF=4.90)

 

***51. ZEB2 drives immature T-cell lymphoblastic leukemia development via altered IL-7 receptor signalling and enhanced tumor-initiating potential. Goossens, S., Radaelli, E., Blanchet, O., Durinck, K., Van der Meulen, J., Peirs, S., Taghon, T., Tremblay, C., Costa, M., Farhang Ghahremani, M., De Medts, J., Bartunkova, S., Haigh, K., Schwab, C., Farla, N., Pieters, T., Matthijssens, F., Van Roy, N., Best, J.A., Deswarte, K., Bogaert, P., Carmichael, C., Rickard, A., Suryani, S., Bracken, L.S., Alserihi, R., Canté-Barrett, K., Haenebalcke, L., Clappier, E., Rondou, P., Slowicka, K., Huylebroeck, D., Goldrath, A.W., Janzen, V., McCormack, M.P., Lock, R.B., Curtis, D.J., Harrison, C., Berx, G., Speleman, F., Meijerink, J.P.P., Soulier, J., Van Vlierberghe, P. and Haigh, J.J.

Nature Communications, Jan 7; 6: 5794 (2015) (IF=12.35)

 

2014

 

50. Immunohistological Description of Nongestational Ovarian Choriocarcinoma in Two Female Mice with Conditional Loss of Trp53 Driven by the Tie2 Promoter. Castiglioni V, Ghahremani MF, Goossens S, De Maglie M, Ardizzone M, Haigh JJ, Radaelli E. 

Vet Pathol. 52(4):752-6 (2014) (IF=1.79)

 

49. Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression. Denecker, G., Vandamme, N., Akay, O., Koludrovic, D., Taminau, J., Lemeire, K., Gheldof, A., De Craene, B., Van Gele, M., Brochez, L. Udupi, G., Rafferty, M., Balint, B., Gallagher, W., Ghanem, G.,  Huylebroeck, D., Haigh, J.J., van den Oord, J.,  Larue, L.,  Davidson, I., Marine, J.C. Berx G.  

Cell Death Differ 21(8):1250-61 (2014) (CIT=71) (IF=8.0)

 

48. Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice. Farhang Ghahremani, M., Radaelli, E., Haigh, K., Bartunkova, S. Haenebalcke, L., Marine, J.C. Goossens, S., Haigh, J.J.

Cell Cycle (2014) May 1;13(9):1501-7 (2014) (IF=3.30)

 

47. ZEB2-transgene expression in the epidermis compromises the integrity of the epidermal barrier through the repression of different tight junction proteins. Tatari MN, De Craene B, Soen B, Taminau J, Vermassen P, Goossens S, Haigh K, Cazzola S, Lambert J, Huylebroeck D, Haigh J.J. Berx, G.

Cell Mol Life Sci 71(18):3599-609 (2014) (IF=6.27)

 

2013

 

46. Beta-Actin Is Involved in Modulating Erythropoiesis during Development by Fine-Tuning Gata2 Expression Levels. Tondeleir, D.; Drogat, B.; Slowicka, K.; Bakkali, K.; Bartunkova, S.; Goossens, S.; Haigh, J. J.*, Ampe, C.* 

PloS one 8 6 e67855 (2013) * Co-last corresponding author (IF=3.54)

 

***45. Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1. van den Berghe, V.; Stappers, E.; Vandesande, B.; Dimidschstein, J.; Kroes, R.; Francis, A.; Conidi, A.; Lesage, F.; Dries, R.; Cazzola, S.; Berx, G.; Kessaris, N.; Vanderhaeghen, P.; van Ijcken, W.; Grosveld, F. G.; Goossens, S.; Haigh, J. J.; Fishell, G.; Goffinet, A.; Aerts, S.; Huylebroeck, D.; Seuntjens, E.

Neuron 77 1 70-82 (2013) (IF=14.3) (CIT=73)

 

44. Efficient ROSA26-Based Conditional and/or Inducible Transgenesis Using RMCE-Compatible F1 Hybrid Mouse Embryonic Stem Cells. Haenebalcke, L.; Goossens, S.; Naessens, M.; Kruse, N.; Ghahremani, M. F.; Bartunkova, S.; Haigh, K.; Pieters, T.; Dierickx, P.; Drogat, B.; Nyabi, O.; Wirth, D.; Haigh, J. J.

Stem Cell Rev 9(6):774-85 (2013) (IF=2.79)

 

43. Endothelial VEGF Sculpts Cortical Cytoarchitecture. Li, S.; Haigh, K. Haigh, J.J.*; Vasudevan, A*. *Co-last author

J Neurosci 33 37 14809-14815 (IF=5.97)

 

42. Gata3 antagonizes cancer progression in Pten-deficient prostates. Nguyen, A. H.; Tremblay, M.; Haigh, K.; Koumakpayi, I. H.; Paquet, M.; Pandolfi, P. P.; Mes-Masson, A. M.; Saad, F.; Haigh, J. J.; Bouchard, M.

Hum Mol Genet 15;22(12):2400-10 (2013) (IF=4.90)

 

***41. Identification of a clonally expanding haematopoietic compartment in bone marrow. Wang, L.; Benedito, R.; Bixel, M. G.; Zeuschner, D.; Stehling, M.; Savendahl, L.; Haigh, J. J.; Snippert, H.; Clevers, H.; Breier, G.; Kiefer, F.; Adams, R. H. 


EMBO J 32 2 219-30 (2013) (IF=9.79) (CIT=61)

 

40. Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis. Vanhooren V, Vandenbroucke RE, Dewaele S, Van Hamme E, Haigh JJ, Hochepied T, Libert C. 

Plos One 8 12 e79883 (2013) (IF=3.54)

 

39. The ROSA26-iPSC mouse: a conditional, inducible, and exchangeable resource for studying cellular (De)differentiation. Haenebalcke, L.; Goossens, S.; Dierickx, P.; Bartunkova, S.; D'Hont, J.; Haigh, K.; Hochepied, T.; Wirth, D.; Nagy, A.; Haigh, J. J.

Cell Rep 3 2 335-41 (2013) (IF=8.03)

 

38. The p53 family and VEGF regulation: "It's complicated". Farhang Ghahremani, M.; Goossens, S.; Haigh, J. J.


Cell Cycle 12 9 1331-2 (2013) (Review) (IF=3.30)

 

37. p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway. Farhang Ghahremani, M.; Goossens, S.; Nittner, D.; Bisteau, X.; Bartunkova, S.; Zwolinska, A.; Hulpiau, P.; Haigh, K.; Haenebalcke, L.; Drogat, B.; Jochemsen, A.; Roger, P. P.; Marine, J. C.; Haigh, J. J.

Cell Death Differ (2013) 20 7 888-97 (CIT=56) (IF=8.0)

 

2012

 

36. Efficient and user-friendly pluripotin-based derivation of mouse embryonic stem cells. Pieters, T.; Haenebalcke, L.; Hochepied, T.; D'Hont, J.; Haigh, J. J.; van Roy, F.; van Hengel, J. 

Stem Cell Rev 8 3 768-78 (2012) (IF=2.79)

 

***35. Formation of the collateral circulation is regulated by vascular endothelial growth factor-A and a disintegrin and metalloprotease family members 10 and 17. Lucitti, J. L.; Mackey, J. K.; Morrison, J. C.; Haigh, J. J.; Adams, R. H.; Faber, J. E. 

Circ Res 111 12 1539-50 (2012) (IF=13.97) (CIT=66)

 

***34. MDM4 is a key therapeutic target in cutaneous melanoma. Gembarska, A.; Luciani, F.; Fedele, C.; Russell, E. A.; Dewaele, M.; Villar, S.; Zwolinska, A.; Haupt, S.; de Lange, J.; Yip, D.; Goydos, J.; Haigh, J. J.; Haupt, Y.; Larue, L.; Jochemsen, A.; Shi, H.; Moriceau, G.; Lo, R. S.; Ghanem, G.; Shackleton, M.; Bernal, F.; Marine, J. C. 

Nature Medicine 18(8):1239-47 (2012) (IF=32.62) (CIT=211)

 

33. Opposing roles for Hoxa2 and Hoxb2 in hindbrain oligodendrocyte patterning. Miguez, A.; Ducret, S.; Di Meglio, T.; Parras, C.; Hmidan, H.; Haton, C.; Sekizar, S.; Mannioui, A.; Vidal, M.; Kerever, A.; Nyabi, O.; Haigh, J.; Zalc, B.; Rijli, F. M.; Thomas, J. L.

 J Neurosci 32 48 17172-85. (2012) (IF=5.97)

 

32. Tissue-wide overexpression of alpha-T-catenin results in aberrant trophoblast invasion but does not cause embryonic mortality in mice. Tyberghein, K.; Goossens, S.; Haigh, J. J.; van Roy, F.; van Hengel, J.


Placenta 33 7 554-60 (2012). (IF=2.79)

 

31. VEGF-independent cell-autonomous functions of HIF-1alpha regulating oxygen consumption in fetal cartilage are critical for chondrocyte survival. Maes, C.; Araldi, E.; Haigh, K.; Khatri, R.; Van Looveren, R.; Giaccia, A. J.; Haigh, J. J.; Carmeliet, G.; Schipani, E. 

J Bone Miner Res 27 3 596-609 (2012) (CIT=55) (IF=0.52)

 

2011

 

***30. A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours. Beck, B.; Driessens, G.; Goossens, S.; Youssef, K. K.; Kuchnio, A.; Caauwe, A.; Sotiropoulou, P. A.; Loges, S.; Lapouge, G.; Candi, A.; Mascre, G.; Drogat, B.; Dekoninck, S.; Haigh, J. J.; Carmeliet, P.; Blanpain, C.


Nature 478 7369 399-403. (2011) (IF=40.14). (CIT=334)

 

29. Neuronal FLT1 receptor and its selective ligand VEGF-B protect against retrograde degeneration of sensory neurons. Dhondt, J.; Peeraer, E.; Verheyen, A.; Nuydens, R.; Buysschaert, I.; Poesen, K.; Van Geyte, K.; Beerens, M.; Shibuya, M.; Haigh, J. J.; Meert, T.; Carmeliet, P.; Lambrechts, D. 

Faseb J 25 5 1461-73 (2011) (IF=5.59)

 

***28. The EMT regulator Zeb2/Sip1 is essential for murine embryonic hematopoietic stem/ progenitor cell differentiation and mobilization. Goossens, S.; Janzen, V.; Bartunkova, S.; Yokomizo, T.; Drogat, B.; Crisan, M.; Haigh, K.; Seuntjens, E.; Umans, L.; Riedt, T.; Bogaert, P.; Haenebalcke, L.; Berx, G.; Dzierzak, E.; Huylebroeck, D.; Haigh, J. J.

Blood 117 21 5620-30. (2011) (IF=15.13) (CIT=68)

 

***27. VEGF mediates commissural axon chemoattraction through its receptor Flk1. Ruiz de Almodovar, C.; Fabre, P. J.; Knevels, E.; Coulon, C.; Segura, I.; Haddick, P. C.; Aerts, L.; Delattin, N.; Strasser, G.; Oh, W. J.; Lange, C.; Vinckier, S.; Haigh, J.; Fouquet, C.; Gu, C.; Alitalo, K.; Castellani, V.; Tessier-Lavigne, M.; Chedotal, A.; Charron, F.; Carmeliet, P. 

Neuron 70 5 966-78 (2011) (IF=14.3) (CIT=115)

 

 

2010

 

***26. Identification of a co-activator that links growth factor signalling to c-Jun/AP-1 activation. Davies, C. C.; Chakraborty, A.; Cipriani, F.; Haigh, K.; Haigh, J. J.; Behrens, A.

Nat Cell Biol 12 10 963-72 (2010) (IF=19.04)

 

***25. Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery. Storkebaum, E.; Ruiz de Almodovar, C.; Meens, M.; Zacchigna, S.; Mazzone, M.; Vanhoutte, G.; Vinckier, S.; Miskiewicz, K.; Poesen, K.; Lambrechts, D.; Janssen, G. M.; Fazzi, G. E.; Verstreken, P.; Haigh, J.; Schiffers, P. M.; Rohrer, H.; Van der Linden, A.; De Mey, J. G.; Carmeliet, P. 

Circulation 122 3 273-81 (2010) (IF=18.88)

 

***24. Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones. Maes, C.*; Goossens, S.*; Bartunkova, S*.; Drogat, B.; Coenegrachts, L.; Stockmans, I.; Moermans, K.; Nyabi, O.; Haigh, K.; Naessens, M.; Haenebalcke, L.; Tuckermann, J. P.; Tjwa, M.; Carmeliet, P.; Mandic, V.; David, J. P.; Behrens, A.; Nagy, A.; Carmeliet, G.; Haigh, J. J.

EMBO J 29 2 424-41 (2010) (IF=9.79) (CIT=114)

 

23. Matrix-binding vascular endothelial growth factor (VEGF) isoforms guide granule cell migration in the cerebellum via VEGF receptor Flk1. Ruiz de Almodovar, C.; Coulon, C.; Salin, P. A.; Knevels, E.; Chounlamountri, N.; Poesen, K.; Hermans, K.; Lambrechts, D.; Van Geyte, K.; Dhondt, J.; Dresselaers, T.; Renaud, J.; Aragones, J.; Zacchigna, S.; Geudens, I.; Gall, D.; Stroobants, S.; Mutin, M.; Dassonville, K.; Storkebaum, E.; Jordan, B. F.; Eriksson, U.; Moons, L.; D'Hooge, R.; Haigh, J. J.; Belin, M. F.; Schiffmann, S.; Van Hecke, P.; Gallez, B.; Vinckier, S.; Chedotal, A.; Honnorat, J.; Thomasset, N.; Carmeliet, P.; Meissirel, C.

J Neurosci 30 45 15052-66 (2010) (CIT=69) (IF=5.97)

 

***22. VEGFR2 (KDR/Flk1) signaling mediates axon growth in response to semaphorin 3E in the developing brain. Bellon, A.; Luchino, J.; Haigh, K.; Rougon, G.; Haigh, J.; Chauvet, S.; Mann, F. 

Neuron 66 2 205-19 (2010) (IF=14.3) (CIT=94)

 

***21. Vegf regulates embryonic erythroid development through Gata1 modulation. Drogat, B.; Kalucka, J.; Gutierrez, L.; Hammad, H.; Goossens, S.; Farhang Ghahremani, M.; Bartunkova, S.; Haigh, K.; Deswarte, K.; Nyabi, O.; Naessens, M.; Ferrara, N.; Klingmuller, U.; Lambrecht, B. N.; Nagy, A.; Philipsen, S.; Haigh, J.

Blood 116 12 2141-51 (2010) (IF=15.13)

 

20. Widespread overexpression of epitope-tagged Mdm4 does not accelerate tumor formation in vivo. De Clercq, S.; Gembarska, A.; Denecker, G.; Maetens, M.; Naessens, M.; Haigh, K.; Haigh, J. J.; Marine, J. C.


Mol Cell Biol 30 22 5394-405 (2010) (IF=3.81)

 

***19. Efficient mouse transgenesis using Gateway-compatible ROSA26 locus targeting vectors and F1 hybrid ES cells. Nyabi, O.; Naessens, M.; Haigh, K.; Gembarska, A.; Goossens, S.; Maetens, M.; De Clercq, S.; Drogat, B.; Haenebalcke, L.; Bartunkova, S.; De Vos, I.; De Craene, B.; Karimi, M.; Berx, G.; Nagy, A.; Hilson, P.; Marine, J. C.; Haigh, J. J.

Nucleic Acids Res 37 7 e55 (2009) (IF=11.56) (CIT=82)

 

Book Chapters

 

5. Cre/lox – Transgenics. Haenebalcke L, Haigh J.J.

Brenner's Encyclopedia of Genetics (Second Edition) (2013) Editors: Sydney Brenner Jeffrey Miller

 

4. The role of EMT modulators in hematopoiesis and leukemic transformation. Goossens, S., Haigh J.J.

Hematology - Science and Practice (2012), InTech, Editor. Charles H. Lawrie

Research Funding

Obtained Competitive Research Funding (since 2009, in CAN $)

 

NHMRC Australia (2013-present)

 

GNT1141081-Roles of the EMT transcription factors in epigenetic remodeling and myeloid cell transformation. Duration: 2018-2020 (3 years) Amount: $809,519.50

Role: Principle Investigator

 

GNT1104441-Role of ZEB/NuRD interactions in Hematopoiesis and Lymphoid

Malignancies. Duration: 2016-2018 (3 years) Amount: $810,497.00

Role: Principle Investigator

 

GNT1151485-Finding Novel RNAs in Heart and Blood Vessel Development.

Duration: 2013-2016 (3 years) Amount: $606,767.85

Role: Principle Investigator

 

GNT1047995 -Novel Genes Involved in Leukemia Development.

Duration: 2013-2016 (3 years) Amount: $628,237.35

Role: Principle Investigator

 

GNT1086662-Eradicating leukemic stem cells by targeting the arginine methyltransferase PRMT5. Duration: 2015-2018 (4 years)

Amount: $50,000

Role: Co-investigator

 

Belgium (2009-2013)

 

IUAP-P707-Belgium Interuniversity Attraction Poles-


Duration: 2012-2016 (5 years)

Amount: $207,000

Role: Co-Investigator

 

Belgium Federation Against Cancer-F49

Duration: 2012-2014 (3 years)

Amount: $215,000

Role: Principle Investigator

 

FWO-G.0568.13N (Flemish Basic Science Foundation), Belgium

Duration: 2012-2015 (4 years)

Amount: $128,000

Role: Principle Investigator

 

Belgium Federation Against Cancer

Duration: 2009-2012 (4 years)

Amount: $283,000

Role: Principle Investigator

 

FWO project grant

Duration: 2008-2011 (4 years)

Amount: $180,000

Role: co-investigator

 

IUAP Belgium Interuniversity Attraction Poles

Duration: 2007-2010 (4 years)

Amount: $257,000

Role: Co-investigator

 

FWO project grant

Duration: 2007-2010 (4 years)

Amount: $129,000

Role: Co-investigator

 

Conference Invitations and Presentations (since 2009)

 

-Monash University Heart Research Symposium,

Invited Speaker, Melbourne Australia, 2017

-The First Harbin International Symposium on Leukemia and Other Malignancies:

Pathogenesis and Therapeutics,

Invited Keynote Speaker, Harbin, China, 2016

-Australasian Society for Stem Cell Research (ASSCR) annual meeting,

Young investigator event panel member, Hunter Valley, Sydney Australia, 2015

-2nd Cell Reprogramming Australia's The Making of Reprogramming Conference,

Invited Speaker, Melbourne, Australia, 2014

-7th International Garvan Signaling Symposium,

Invited Speaker, Sydney, Australia, 2014

-New Directions in Leukemia Research (NDLR),

Plenary Speaker, Noosa, Australia, 2014

-International Society for Stem Cell Research (ISSCR) Annual Meeting,

Invited Sessional Speaker Boston, USA, 2013

-6th Mouse Genetics Meeting,

Invited Speaker, Montpellier, France, 2013

-1st International Aegean conference on Stem Cell Biology,

Invited Speaker, Crete, Greece, 2012

-Sixth International Workshop on Innovative Mouse Models, 

Plenary Speaker, Lieden, The Netherlands, 2011

-8th International Conference on BMPs,

Session Chair, Leuven, Belgium, 2010

-14th International European Hematology Association (EHA) Conference, 

Plenary Speaker Berlin, Germany, 2009

 

Institutional Invited Talks (since 2009)

 

-Goodman Cancer Centre (Dr. Maxime Bouchard), McGill University (2017)

-University of Sydney (Dr. Timothy Newsome) Sydney, Australia (2014)

-University of Adelaide (Dr. Quentin Schwarz) Adelaide, Australia (2014)

-Garvan Research Institute (Dr. Paul Timpson) Sydney, Australia (2014)

-Queensland Institute for Medical Research (Dr. Frank Gannon) Brisbane, Australia (2012)

-Victor Chang Cardiac Research Center (Dr. Bob Graham) Sydney, Australia 2011

-School of Biomedical Sciences (Dr. Walter Thomas) University of Queensland, Brisbane, Australia (2011)

-Queen’s University (Dr. Peter Greer) Kingston, Canada (2010)

-Cancer Research UK (Dr. Axel Behrens) London, UK (2009)

 

Academic and Professional Service

 

-Journal Peer Reviewer for > 20 journals in the past 10 years stem cell biology and cancer. Top journals include Stem Cell Reports, EMBO, Blood and Development.

-Journal Editorial Board Member for Frontiers in Stem Cell Research journal (2014) and AIMS Cell and Tissue Engineering (2016).

-National Grant Reviewer at the NHMRC (since 2012) and NHMRC Grant Review Panel (GRP) member in 2017.

-International Grant Reviewer for the FWO and FNRS, Belgium as a panel member (2013) and external reviewer (since 2013)

-External Expert Adviser for the Cancer Research UK mouse facility (2013).

-Nominated Rapporteur by Australian Academy of Sciences for the generation of a policy document concerning the future of regenerative medicine in Australia (2015).

-Co­-chair the group leader committee at the Flanders Institute of Biotechnology (VIB) in Belgium (2012-2013) and at the ACBD (2014) to improve communication and develop research strategy initiatives.

 

 

AWARDS

 

Queen’s University Graduate Award:

01/09/1994-28/10/1995

Value=$5000 CAN

 

Vienna Biocentre International PhD Studentship

15/11/95-15/12/99     

Value=$20 000 CAN/year

 

National Cancer Institute of Canada (NCIC) Terry Fox Postdoctoral Fellowship

01/06/2001-31/03/2004

Value=$40 000 CAN/year

 

*Tier II Canada Research Chair in Regenerative Medicine

(Queen’s University, Canada) 01/01/2011-01/01/2016

Value=$700,000 CAN ($100K/year salary support + 200K CFI component)

*(Declined)

 

Larkins Fellowship-Monash University

01/08/2013-01/08/2015 

Value=$630K CAN ($480K-salary support and consumables, $150K-Equipment 

 




RIOH gratefully acknowledges the generous support of



CCMB_Logo RIOH is a joint institute of CancerCare Manitoba and University of Manitoba UofM_Logo