Welcome to the
Cardiac Morphogenesis Laboratory

Smith Laboratory page

Smith Laboratory

  • Kelly Smith laboratory
     
    Kelly Smith
    Principal Investigator Read more
  • Smith Group Staff
     
    Angela Jeanes
    Postdoctoral Researcher
  • Sam Capon from Smith Laboratory
     
    Sam Capon
    PhD student Read more
  • Jess from the Smith Laboratory
     
    Jessica De Angelis
    PhD Student Read more
  •  
    Vanessa Raileanu
    PhD Student Read more
  • Smith Group Staff
     
    Jason Da Silva
    Research Assistant

Our survival is contingent on a correctly formed and functioning heart. It’s architecture is so precise that even small deviations from its normal structure can have fatal consequences, in the form of congenital heart defects. The complexity of the heart is achieved during embryonic development, beginning with simple tissue primordia that proliferate, migrate, differentiate, integrate and reorganize in an exact sequence of events to form the final organ. The vasculature is also centrally important in cardiovascular diseases and in cancer progression. We aim to better understand how the vasculature forms during development and to translate our findings into a deeper understanding of disease. We study several aspects of vascular development and biology.
 

The Smith laboratory, led by Kelly Smith, is located at the Institute for Molecular Bioscience.  Understanding the programming of these events, including the genetic networks that regulate it, the cell-to-cell interactions involved and the biomechanical forces that contribute to its development are the primary interests of my research. It is appreciated that any disturbance in these early developmental events will result in congenital heart defects. Understanding how the heart forms therefore provides an essential framework for dealing with these birth defects.
 

The Smith Lab

  • 6

    Researchers

  • 18

    Publications

  • 3

    Projects

  • 289

    Citations

 

Smith lab research

Cardiac development

At the earliest stages of cardiac development, cardiac progenitor cells reside as bilateral populations in the lateral plate mesoderm. These populations begin to differentiate as they migrate towards the embryonic midline and fuse. Their manner of fusion results in the encapsulation of the endocardium (the future inner lining of the heart) within a myocardial layer (the beating component of the heart). From here, the heart elongates to form the primitive linear heart tube. As the heart tube forms, it breaks left-right symmetry, commencing the onset of cardiac looping. At this time, the heart has begun to beat and circulation is established therefore further development occurs whilst the organ is already functioning.

Kelly Smith Lab research


Following on from linear heart tube formation, distinct constrictions appear that dictate where the heart will bend and fold. At these sites, the endocardial cushions develop, which will later give rise to the valves and septa of the heart. These cushions are swellings between the endocardial and myocardial layers, which consist of an extracellular matrix and (predominantly) invading endocardial cells that delaminate and undergo endothelial-to-mesenchymal transition. Adjacent to the endocardial cushions are the developing chambers. Cardiomyocytes in the future chambers alter their shape and, in some instances will proliferate, resulting in an expansion known as chamber ballooning. By 48 hours post fertilization in the fish, 10 days post coitus (dpc) in the mouse and 32 dpc in human, the heart is already made up of multiple and distinct chambers for collecting and pumping blood, primitive valves that are already preventing backflow and correctly synchronized beating chambers that ensure efficient circulation to deliver blood to the developing embryo.
It is these early stages of cardiac development that are of primary interest to our lab. Using both forward and reverse genetic approaches, we are attempting to systematically tease out the genetics and cell biology regulating early cardiac development. Major research themes of my research include understanding:
 

  • Cellular interactions in the cardiac tube

  • Boundary establishment and maintenance within the heart, and

  • Compartment identity

 

 

 

CURRENT RESEARCH PROJECTS

 

Understanding the differentiation of the endocardium
2017-2020, ARC Discovery Project Grant
Collaborators: Dr Kelly Smith, Dr Nathan Palpant

 

Examining an extracellular matrix regulator required for cardiovascular development
2016-2019, NHMRC Project Grant
Collaborators: Dr Kelly Smith, Dr Mathias Francois, AProf Carol Wicking, Dr Enzo Porrello, Dr Ben Hogan

 

Characterisation of a newly identified, indispensible, transcriptional regulator of lymphangiogenesis
2016-2018, NHMRC Project Grant
Collaborators: Dr Ben Hogan, Dr Cas Simons, Dr Kelly Smith, Dr Mathias Francois, Dr Gregory Baillie, Professor Peter Koopman

 

Functional and molecular characterisation of a novel regulator of angiogenesis
2013-2016, NHMRC Project Grant
Collaborators: Dr Kelly Smith, Dr Ben Hogan, Dr Mathias Francois

 

 

CURRENT FELLOWSHIPS

 

Genetic dissection of cardiac morphogenesis
2013-2016, ARC Future Fellowship, Dr Kelly Smith

 

2015-2016, Advancing Women Researchers Grant 2015, The University of Queensland, Dr Kelly Smith

 

 

CURRENT PHD PROJECTS

 

Identification and characterisation of cardiovascular zebrafish mutants

 

Specification and migration of cardiac precursor cells during vertebrate cardiac development

 

Defining genetic and biomechanical regulators of cardiac looping

 

 

RECENTLY COMPLETED RESEARCH PROJECTS

 

Characterisation of conserved Sox18-dependent regulators of lymphatic vascular development
2013-2015, NHMRC Project Grant
Collaborators: Dr Ben Hogan, Dr Cas Simons, Dr Kelly Smith, Dr Mathias Francois, Dr Gregory Baillie, Prof Peter Koopman

 

 

 

 

Gregory Baillie
Senior Core Bioinformatics Officer, Institute for Molecular Bioscience, The University of Queensland, AUSTRALIA
Characterisation of a newly identified, indispensible, transcriptional regulator of lymphangiogenesis

 

Sally Dunwoodie
Victor Chang Cardiac Research Institute, Sydney, AUSTRALIA
Mutation identification in CHD patients.

 

Diane Fatkin
Victor Chang Cardiac Research Institute, Sydney, AUSTRALIA
Analysis of zebrafish mutants.

 

Mat Francois
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, AUSTRALIA
Examining an extracellular matrix regulator of cardiovascular development. Characterisation of a newly identified, indispensible, transcriptional regulator of lymphangiogenesis. Functional and molecular characterisation of a novel regulator of angiogenesis. Analysis of vascular genes in mouse models.

 

Joan Heath
Walter and Eliza Hall Institute of Medical Research, Melbourne, AUSTRALIA
NGS positional cloning of zebrafish mutants.

 

Ben Hogan
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, AUSTRALIA
Characterisation of a newly identified, indispensible, transcriptional regulator of lymphangiogenesis. Examining an extracellular matrix regulator of cardiovascular development and forward genetic screening in zebrafish embryos. Analysis of vascular defects in zebrafish mutants.

 

Peter Koopman
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, AUSTRALIA
Characterisation of a newly identified, indispensible, transcriptional regulator of lymphangiogenesis.

 

Enzo Porrello
School of Biomedical Sciences, The University of Queensland, AUSTRALIA
Examining an extracellular matrix regulator of cardiovascular development

 

Quenten Schwarz
Centre for Cancer Biology, SA Pathology, Adelaide, AUSTRALIA
Analysis of zebrafish mutants.

 

Cas Simons & Ryan Taft
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, AUSTRALIA
Characterisation of a newly identified, indispensible, transcriptional regulator of lymphangiogenesis. WNGS positional cloning of zebrafish mutants. Validating CRISPR technology. Mutation identification in CHD patients.

 

Carol Wicking
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, AUSTRALIA
Examining an extracellular matrix regulator of cardiovascular development and analysis of CHD genes in the mouse models.

 

 

INTERNATIONAL COLLABORATIONS

 

Jeroen Bakkers
Hubrecht Institute, Utrecht, NETHERLANDS
Analysis of zebrafish mutants.

 

Vincent Christoffels
Heart Failure Research Center, Academic Medical Center, Amsterdam, NETHERLANDS
Analysis of novel cardiac mutants.

 

Debbie Yelon
Division of Biological Sciences, University of California, San Diego, UNITED STATES
Analysis of gene function in heart development.

 

 

 

 

Angela Jeanes, Vanessa Raileanu, Kelly Smith, Alisha Tromp and Jessica De Angelis

 

 

 

Smith lab discoveries in the media

 
TELEVISION AND NEWSPAPER REPORTS

Our research has featured in the following media reports:
 

Channel Ten Australia logoSep 2011, Totally Wild, Zebrafish Heart Research with Dr Kelly Smith.






Channel 7 News Australia logo26 Jun 2011, Sunday Mail, Brisbane, Perth, Tasmania, Tiny fish helping to battle cancer.
Zebrafish aid in heart gene discovery.




 

 

 

THE UNIVERSITY OF QUEENSLAND PRESS RELEASES
 

16 Nov 2011    IMB researchers snare ARC fellowships

Dr Kelly Smith was offered both a $673,528 Future Fellowship and a $375,000 Discovery Early Career Researcher Award to discover new genes involved in cardiac development.
UQ news article


15 Nov 2011     UQ dominates ARC Fellowship results

Based on the Kelly Smith’s performance in the highly competitive Australian Research Council funding arena.
UQ news article

 


THE INSTITUTE FOR MOLECULAR BIOSCIENCES NEWS

1 Nov 2016     $4.5 million for IMB-led discovery research

UQ Centre for Cardiac and Vascular Biology research teams led by Dr Kelly Smith and Dr Nathan Palpant have been awarded funding by the Australian Research Council for a groundbreaking new discovery research project, 'Understanding the differentiation of the endocardium". UQ CCVB news article
IMB news article

 

 

 

9 Nov 2015     NHMRC awards more than $11 million to IMB research

Based on Kelly Smith's NHMRC funding award, in collaboration with Dr Mat Francois, to understand how defective copies of specific genes, that are required for the heart to correctly assemble and function, result in cardiovascular disease (CVD). This research will lead to better diagnosis and treatment for CVD, the leading cause of death in Australia.
IMB news article

 

19 Oct 2012     IMB researchers awarded $12.8M in funding from NHMRC

Based on NHMRC funding awarded to Dr Kelly Smith, part of the $12.8 million awarded to IMB scientists for health and medical research in 2013.
IMB news article

 

16 Nov 2011    Heart development research among projects to score $2.7M in fellowships

Dr Kelly Smith was offered both a $673,528 Future Fellowship and a $375,000 Discovery Early Career Researcher Award from the Australian Research Council to discover new genes involved in cardiac development. “The human heart is critical for survival and yet, despite its importance, we still lack a basic understanding of how it forms,” Dr Smith said.

IMB news article
 

 

21 Jun 2011    Zebrafish aid in heart gene discovery award

Discovery of the new gene, wickham, involved in heart development snagged an Kelly Smith a prize at the Queensland Health and Medical Research Awards.
IMB news article


 

 
 
 

Smith lab publications

 
 
 
 

 

16. De Angelis JE*, Lagendijk AK*, Chen H, Tromp A, Bower NI, Tunny KA, Brooks AJ, Bakkers J, Francois M, Yap AS, Wicking C, Hogan BM#, Smith KA#. Tmem2 regulates embryonic Vegf-signaling by controlling Hyaluronic acid turnover. Developmental Cell 2017. Jan 23 Volume 40, Issue 2, p123–136. *Joint first authors #Joint senior authors. Pubmed

 

15. Capon SJ, Baillie GJ, Bower NI, da Silva JA, Paterson S, Hogan BM, Simons C, Smith KA. Utilising polymorphisms to achieve allele-specific genome editing in zebrafish. Biology Open 2017 Jan 15;6(1):125-131. Pubmed

 

14. Koltowska K, Paterson S, Bower NI, Baillie GJ, Lagendijk AK, Astin JW, Chen H, Francois M, Crosier PS, Taft RJ, Simons C, Smith KA, Hogan BM. mafba is a downstream transcriptional effector of Vegfc signaling essential for embryonic lymphangiogenesis in zebrafish. Genes & Development 2015 Aug 1;29(15):1618-30. Cover art

Koltowska et al 2015

 

 


13. Coxam B, Neyt C, Grassini DR, Le Guen L, Smith KA, Schulte-Merker S, Hogan BM. Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (cad) regulates Notch signaling and vascular development in zebrafish. Developmental Dynamics. 2015 Jan; 244(1):1-9.

12. Coxam B, Sabine A, Bower NI, Smith KA, Pichol-Thievend C, Skoczylas R, Astin JW, Frampton E, Jaquet M, Crosier PS, Parton RG, Harvey NL, Petrova TV, Schulte-Merker S, Francois M, Hogan BM. Pkd1 Regulates Lymphatic Vascular Morphogenesis during Development. Cell Reports. 2014. 7(3):623-33.

11. Duong T, Koltowska K, Pichol-Thievend C, Le Guen L, Fontaine F, Smith KA, Truong V, Skoczylas R, Stacker SA, Achen MG, Koopman P, Hogan BM, Francois M. VEGFD regulates blood vascular development by modulating SOX18 activity. Blood. 2014. 123(7):1102-12.

10. Kartopawiro J, Bower NI, Karnezis T, Kazenwadel J, Betterman KL, Lesieur E, Koltowska K, Astin J, Crosier P, Vermeren S, Achen MG, Stacker SA, Smith KA, Harvey NL, François M, Hogan BM. Arap3 is dysregulated in a mouse model of hypotrichosis-lymphedema-telangiectasia and regulates lymphatic vascular development. Human Molecular Genetics. 2014. 23(5):1286-97.

9. Noël ES, Verhoeven M, Lagendijk AK, Tessadori F, Smith K, Choorapoikayil S, den Hertog J,Bakkers J. A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality. Nature Communications. 2013. 4:2754.

8. de Pater E, Ciampricotti M, Priller F, Veerkamp J, Strate I, Smith K, Lagendijk AK, Schilling TF, Herzog W, Abdelilah-Seyfried S, Hammerschmidt M, Bakkers J. Bmp signaling exerts opposite effects on cardiac differentiation. Circulation Research. 2012. 110(4):578-87.

7. Smith KA*, Noel E*, Thurlings I, Rehmann H, Chocron S, & Bakkers J. Bmp and Nodal Independently Regulate lefty1 Expression to Maintain Unilateral Nodal Activity During Left-Right Axis Sepcification in Zebrafish. PLoS Genetics. 2011. 7(9):e1002289. *Equal contribution

6. Smith KA*, Lagendijk AK, Courtney A, Hogan BM, Wicking C & Bakkers J*. Transmembrane protein 2 (tmem2) is required to regionally restrict atrioventricular canal boundary and endocardial cushion development. Development. 2011. 138(19):4193-8 *Corresponding author.

Smith et al 2011

 

 

 

5. Joziasse IC*, Smith KA*, Chocron S, van Dinther M, Guryev V, van de Smagt JJ, Cuppen E, Ten Dijke P, Mulder BJ, Maslen CL, Reshey B, Doevendans PA, Bakkers J. ALK2 mutation in a patient with Down's syndrome and a congenital heart defect. European Journal of Human Genetics. 2011. 19(4): 389-93. *equal contribution

4. Smith KA*, Joziasse IC*, Chocron S, van Dinther M, Guryev V, Verhoeven MC, Rehmann H, van der Smagt JJ, Doevendans PA, Cuppen E, Mulder BJ, ten Dijke P and Bakkers J. A dominant-negative ALK2 allele associates with congenital heart defects. Circulation. 2009. 119(24):3062-9. *equal contribution

3. Kovac S*, Smith KA*, Anderson GJ, Burgess JR, Shulkes A, Baldwin GS. Interrelationships between circulating gastrin and iron status in mice and humans. American journal of Physiology (Gastrointestinal and Liver Physiology). 2008. 295(4):G855-61. *equal contribution

2. Smith KA, Chocron S, von der Hardt S, de Pater E, Soufan A, Bussmann J, Schulte-Merker S, Hammerschmidt M, Bakkers J. Rotation and asymmetric development of the zebrafish heart requires directed migration of cardiac progenitor cells. Developmental Cell. 2008. 14(2):287-97.

1. Smith KA, Kovac S, Anderson GJ, Burgess JR, Shulkes A & Baldwin GS. Circulating gastrin is increased in hemochromatosis. FEBS Letters. 2006. 580(26):6195-8 (2011 Impact Factor - 3.538, 11 citations) Smith KA, Patel O, Lachal S, Jennings I, Kemp B, Burgess J, Baldwin GS & Shulkes. Production, secretion, and biological activity of the C-terminal flanking peptide of human progastrin. Gastroenterology. 2006. 131(5):1463-74.

 

2. Lagendijk AK, Smith KA & Bakkers J. Genetics of Congenital Heart Defects: A Candidate Gene Approach. Trends in Cardiovascular Medicine. Invited review. 2010. 20(4):124-8.

1. Joziasse IC, van de Smagt JJ, Smith K, Bakkers J, Sieswerda GJ, Mulder BJ, Doevendans PA. Genes in congenital heart disease: atrioventricular valve formation. Basic Research in Cardiology. 2008. 103(3):216-27.