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Program Director/Principal Investigator (Last, First, Middle): Dixon, Ian M. C.
BIOGRAPHICAL SKETCH
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NAME
POSITION TITLE
Ian M. C. Dixon
Professor
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, and include postdoctoral training.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
University of Manitoba, Winnipeg, Canada
University of Manitoba, Winnipeg, Canada
University of Manitoba, Winnipeg, Canada
University of Toronto, Toronto, Canada
BSc (Hons)
MSc
PhD
PDF
1983
1986
1990
1992
Zoology
Physiology
Physiology
Medicine and Mol Biol
A. Personal Statement
Our work deals with investigation of the signaling pathways responsible for the occurrence of cardiac fibrosis in
the development of pathological cardiac hypertrophy and overt congestive heart failure. Myofibroblasts are not
normally found in healthy heart muscle, but are very common in diseased and failing hearts of various
etiologies.
Thus we are interested in investigating cellular control of myofibroblast contractility, migration and protein
synthesis as these functions all contribute to wound healing and remodeling of extracellular matrix in diseased
hearts.
Remodeling of the cardiac extracellular matrix has become a well-known modifier of cardiac performance and
on-going or chronic wound healing is closely tied to heart failure. We pursue questions as to why natural
inhibitors of wound healing undergo drastically reduced expression in injured or failing hearts. Our laboratory is
known for its work on some of these proteins, including “Ski” – as well, we have addressed the anti-fibrotic
properties of cardiotrophin-1, a cytokine of the IL-6 superfamily. The expression of these naturally occurring
fibrosis-inhibiting proteins are tightly regulated in cardiac wound healing, especially after myocardial infarction.
Adapting their function with the development of a new drug and applying it to failing hearts, may allow us to
alter the course of the progression of heart disease. Thus if we are able to slow down the progression of
fibrosis present in the vast majority of cardiac disease, we will then be able to preserve cardiac function after
the disease has begun to affect the function of heart.
B. Positions and Honors
Current Positions and Honors (chronological order)
1990–1992
Medical Research Council of Canada Post-Doctoral Fellowship
1994–1999
Medical Research Council/Pharmaceutical Manufacturers Association of Canada Scholarship
1997
Pharmacia and UpJohn Award for Young Investigators (International Society for Heart
Research)
2003–2006
Chair, Animal Care Committee, CanAm Bioresearch, Inc. Winnipeg, Manitoba, Canada
2003
Member, Faculty of Graduate Studies Committee to oversee the creation of terms of
reference for the Governor General’s Gold Medal Award (Doctoral Award)
2003-2008
Member, University of Manitoba, Faculty of Graduate Studies Awards Committee
2005-2007
Member, Committee VIII of the SRC of the Heart and Stroke Foundation of Canada
2005
Consultant, Manitoba Health Research Council – Future Directions Symposium
2005-2008
Scientific Officer, CIHR Cardiovascular Sciences “C” operating grant review committee
2006-present
External Reviewer, Michael Smith Foundation for Health Research (MSFHR)
2006
Peer Review Committee Researcher, External Review of the ICRH.
2006
Consultant and external reviewer, HSFO Heart Failure Group at the University of Western
Ontario.
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Program Director/Principal Investigator (Last, First, Middle): Dixon, Ian M. C.
2007-2013
2007-present
2007-present
2007-present
2008
2007-2013
2002
2007
2008
2009
2002-2009
2010
2010-2011
2011
2011
2012-present
2012 2013 2014 2014 2014 2014 2015 2015 -
Internal reviewer, Program Review Team for the Masters and Doctoral Programs in the
Department of Biochemistry and Medical Genetics, University of Manitoba
Director, IMPACT Strategic Training Program Grant
Member – Institute of Cardiovascular Sciences Advisory Council
Chair – Institute of Cardiovascular Sciences “Programs” committee
External reviewer – Alberta Heritage Foundation for Medical Research
Consulting Editor – Cardiovascular Research
Heart and Stroke Foundation of Manitoba: Dr. R.E. Beamish Memorial Award for Excellence
in Cardiovascular Research
Heart and Stroke Foundation of Manitoba: Dr. R.E. Beamish Memorial Award for Excellence
in Cardiovascular Research
Member, Scientific Review Committee of the Heart and Stroke Foundation of Canada
(Committee IVa)
Deputy Chair, Scientific Review Committee of the Heart and Stroke Foundation of Canada
(Committee IVc)
Myles Robinson Heart Health Fund Scholarship
Manitoba Medical Students Association Teaching Award
Deputy Chair, Scientific Review Committee of the Heart and Stroke Foundation of Canada
(Committee IVa)
Organizer – Featured Topic at Experimental Biology 2011 (Communication between
myocytes and fibroblasts), Washington, DC
Manitoba Medical Students Association Teaching Award
Chair, Scientific Review Committee of the Heart and Stroke Foundation of Canada
(Committee IVa)
P.K. Singal Student Scholarship (Trainee Award – Matthew Zeglinski)
U of Manitoba Medical Students’
Keynote Speaker, ICLAF meeting 2014, Mont Tremblant, Quebec, Canada – “Fibrosis in
post-MI heart – identification of key genes”
Director of MatriNET NCE – finalist is nationwide competition for National Centres of
Excellence of Canada
Winner of Oral presentation for Best Poster (trainee – Shivika Gupta); Cardiovascular
Research Day, Institute of Cardiovascular Sciences
Provincial Finalist – 3 minute thesis presentation – (trainee – Emma Ambrose); February
P.K.Singal Student Scholarship (Trainee award – Dr. Morvarid Kavosh)
Member, CIHR Cardiovascular Sciences “C” Committee
Expertise Keywords: cardiac fibrosis; cardiac fibroblast; tissue repair; myofibroblast; Ski; post myocardial
infarction remodeling; extracellular matrix; TGF-β signaling
Training Record: Total: > 110. As primary supervisor: 4 PDF; 21 Graduate; 5 Undergraduate
C. Selected Peer-reviewed Publications (representative of > 78 publications)
1. Dixon IMC. Much ado about bone marrow stem cells: Role in post-myocardial infarct repair. Cardiovasc
Res, 71(4): 609 – 611, 2006. (doi:10.1016/j.cardiores.2006.07.002)
2. Jiang Z-S, Jeyaraman M, Wen G-B, Fandrich RR, Dixon IMC, Cattini PA and Kardami E. High- but not
low-molecular weight FGF-2 causes cardiac hypertrophy in vivo; possible involvement of cardiotrophin-1. J
Mol Cell Cardiol. 42(1): 222 - 233, 2007.
3. Raizman JE, Komljenovic J, Chang R, Deng C, Elimban VV, Freed DH, and Dixon IMC. The participation
of the Na+-Ca2+ exchanger and non-selective cation channels in primary cardiac myofibroblast migration,
contraction, and proliferation. J Cell Physiol, 213(2): 540 - 551, 2007
4. Drobic V, Cunnington RH, Raisman JE, Elimban VV, Rattan SG, and Dixon IMC. Differential and
combined effects of Cardiotrophin-1 and TGF-β1 on cardiac myofibroblast proliferation and contraction.
Am J Physiol Heart and Circ Physiol, 293(2):H1053 - H1064, 2007.
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Program Director/Principal Investigator (Last, First, Middle): Dixon, Ian M. C.
5. Wang B, Omar A, Angelovska T, Drobic V, Jones SC, Rattan SG and Dixon IMC Regulation of collagen
synthesis by inhibitory Smad7 in cardiac myofibroblasts. Am J Physiol Heart and Circ Physiol,
293(2):H1282 – H1290, 2007.
6. Dixon IMC. Working with what we have: Options for myocardial infarct repair. Cardiovasc Res, 76: 377-8
[Electronic publication- Sept 18], 2007.
7. Schram K, Wong K, Rengasamy P, No S, Dixon IMC and Sweeney G. Increased expression and cell
surface localization of MT1-MMP plays a role in stimulation of MMP-2 activity by leptin in neonatal rat
cardiac myofibroblasts. J Mol Cell Cardiol. 2008 May;44(5):874-81. Epub 2008 Mar 12.
8. Espira L, Lamoureux L, Jones SC, Gerard RD, Dixon IMC, Czubryt MP. The basic helix-loop-helix
transcription factor scleraxis regulates fibroblast-mediated collagen synthesis. JMol Cell Cardiol. 47:188195, 2009. Epub 2009 April 10.
9. Cunnington RH, Nazari M and Dixon IMC. C-Ski, Smurf2 and Arkadia as regulators of TGF-β signaling:
New targets for managing myofibroblast function and cardiac fibrosis. Can J Physiol Pharmacol. In press,
2009.
10. Dixon IMC. Periostin is a novel factor in cardiac remodeling following experimental clinical unloading of
the failing heart. Invited Commentary. Ann Thorac Surg. 2009 Dec;88(6):1916-21.
11. Santiago J-J, Dangerfield AL, Rattan SG, Bathe KL, Cunnington RH, Raizman JE, Bedosky KM, Freed DH,
Kardami E, and Dixon IMC. Fibroblasts to myofibroblasts differentiation in vitro: Transitionary markers for
reliable identification of neonatal, adult and human myofibroblasts. Dev Dyn. 2010 Jun;239(6):1573-84
12. Ahmadie R, Santiago JJ, Walker J, Fang T, Le K, Zhao Z, Azordegan N, Bage S, Lytwyn M, Rattan S,
Dixon IM, Kardami E, Moghadasian MH, Jassal DS. A High-Lipid Diet Potentiates Left Ventricular
Dysfunction in Nitric Oxide Synthase 3-Deficient Mice after Chronic Pressure Overload. J Nutr. 2010 Jun
16. [Epub ahead of print]
13. Dixon IMC. The soluble interleukin 6 receptor takes its place in the pantheon of interleukin 6 signaling
proteins. Phenoconversion of cardiac fibroblasts to myofibroblasts. Editorial commentary. Hypertension.
2010 July 6 [Epub ahead of print]
14. Cunnington RH, Wang B, Ghavami S, Bathe KL, Rattan SG, and Dixon IMC. Antifibrotic properties of cSki and its regulation of cardiac myofibroblast phenotype and contractility. Am J Physiol, Cell Physiol,
2011 Jan; 300(1):C176-86. Epub 2010 Oct 13.
15. Dixon IMC and Davies JJ. Fibroblasts are coupled to myocytes in heart muscle by nanotubes: a bigger
and better syncytium? Cardiovasc Res. 2011 Oct 1;92(1):5-6. doi: 10.1093/cvr/cvr216.
16. Ghavami S, Yeganeh B, Stelmack GL, Kashani HH, Sharma P, Cunnington RH, Rattan SG, Bathe K,
Klonisch T, Dixon IMC, Freed DH, and Halayko AJ. Apoptosis, autophagy and ER stress in mevalonate
cascade inhibition-induced cell death of human atrial fibroblasts. Cell Death and Disease 3, e330;
doi:10.1038/cddis.2012.61; published online 21 June 2012.
17. Dixon IMC, Cardiac myofibroblasts: cells out of balance. A new thematic series. Editorial for Fibrogenesis
Tissue Repair. 2012 Sep 3;5(1):14. doi: 10.1186/1755-1536-5-14.
18. Ghavami S, Cunnington RH, Yeganeh B, Davies JJ, Rattan SG, Bathe K, Kavosh M, Los MJ, Freed DH,
Klonisch T, Pierce GN, Halayko AJ, Dixon IMC. Autophagy regulates trans fatty acid-mediated apoptosis
in primary cardiac myofibroblasts. Biochim Biophys Acta. 2012 Dec;1823(12):2274-86. doi:
10.1016/j.bbamcr.2012.09.008. Epub 2012 Sep 28.
19. Zeglinski MR, Hnatowich M, Jassal DS, Dixon IMC. SnoN as a novel negative regulator of TGF-β/Smad
signaling: a target for tailoring organ fibrosis.Am J Physiol Heart Circ Physiol. 2015 Jan 15;308(2):H75H82. doi: 10.1152/ajpheart.00453.2014. Epub 2014 Nov 7. Review.
20. Ghavami S, Gupta S, Ambrose E, Hnatowich M, Freed DH, Dixon IMC. Autophagy and heart disease:
implications for cardiac ischemia-reperfusion damage. Curr Mol Med. 2014;14(5):616-29.
21. Ngo MA, Müller A, Li Y, Neumann S, Tian G, Dixon IMC, Arora RC, Freed DH Human mesenchymal stem
cells express a myofibroblastic phenotype in vitro: comparison to human cardiac myofibroblasts. Mol Cell
Biochem. 2014 Jul;392(1-2):187-204. doi: 10.1007/s11010-014-2030-6. Epub 2014 Apr 2.
22. Cunnington RH, Northcott JM, Ghavami S, Filomeno KL, Jahan F, Kavosh MS, Davies JJ, Wigle JT, Dixon
IMC. The Ski-Zeb2-Meox2 pathway provides a novel mechanism for regulation of the cardiac myofibroblast
phenotype.J Cell Sci. 2014 Jan 1;127(Pt 1):40-9. doi: 10.1242/jcs.126722. Epub 2013 Oct
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Program Director/Principal Investigator (Last, First, Middle): Dixon, Ian M. C.
23. Saeid Ghavami, Ryan H. Cunnington, Shivika Gupta, Behzad Yeganeh, Krista L. Filomeno, Darren H.
Freed, Shu-ru Chen, Thomas Klonisch, Andrew J. Halayko, Emma Ambrose, Rohit Singal and IMC Dixon.
Autophagy is a Regulator of TGF-β1 Induced Fibrogenesis in Primary Human Atrial Myofibroblasts. In
press, Cell Death and Disease, 2015.
D. Research Support
Current and anticipated grant support
•
Role of scleraxis in cardiac collagen gene expression
Operating Grant
Czubryt (PI)
04/14 – 03/19 CIHR
Role: Principal Investigaror
Award Total: $845,000
•
Regulation of scleraxis expression in cardiac myofibroblasts
Grant-in-Aid
Cuzbryt (PI)
07/14 – 06/17 Heart & Stroke Foundation of Canada
Role: Principal Investigator
Award Total: $360,000
•
Ski and Scleraxis interaction in myofibroblast regulation
Grant-in-Aid
Dixon (PI)
09/13 – 08/16 Heart & Stroke Foundation of Canada
Role: Co-Investigator
Approved Award Total: $307,765 (Final allocation TBD)
•
Myofibroblast diversity in tissue engineering
CANUSA Research Project
Dixon/Simari (Co-PI) 10/12 – 06/15 Asper Endowment Fund
Role: Co-Investigator
Award Total: $250,000
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