Hudson Lab - Muscle Tissue Engineering

Our lab is trying to unravel the molecular mechanisms that regulate cardiac regenerative capacity in mammals. We use cutting-edge molecular techniques to understand the epigenetic changes that occur during postnatal heart development and regeneration. Our major research interest is in trying to decipher the mechanisms by which large gene regulatory networks are altered in the heart shortly after birth and to understand how these changes contribute to cardiomyocyte maturation and regenerative arrest. We hope to ultimately unravel key mechanisms that bestow the neonate with regenerative potential and re-activate these processes in adulthood for cardiac repair.

Due to the very limited regenerative capacity of the adult mammalian heart, diseases that result in cardiomyocyte death, such as myocardial infarction, can have devastating consequences for organ function. In contrast, we recently discovered that the mammalian heart harbours a transient potential for regeneration during neonatal life, which is lost shortly after birth. Similar to the zebrafish and axolotl, the neonatal mouse heart can mount a robust regenerative response following myocardial injury (apical resection and myocardial infarction), which appears to be driven by the proliferation of resident cardiomyocytes. The molecular mechanisms that regulate cardiomyocyte proliferative potential and cardiac regenerative capacity in mammals are poorly understood.

View our lab on the UQ Centre for Cardiac and Vascular Biology site

Our laboratory at The University of Queensland in Brisbane, Australia, is trying to unravel the molecular mechanisms that drive cardiac regeneration. Some of the projects currently being pursued in our laboratory include:

 

Post-natal control of cardiac gene regulatory networks.

Epigenetic modifications are critical for the precise temporal regulation of gene expression during heart development. We are trying to map the changes in the genomic landscape during post-natal heart development to identify the molecular drivers of cardiac regeneration during early developmental stages.

 

Modelling human heart development using human cardiac organoids.

Recent advances in stem cell sciences and tissue engineering are providing unparalleled opportunities to generate human heart tissues in a dish. We are using human cardiac organoids to understand the mechanisms that regulate the developmental maturation of human heart muscle.

 

Functional genomic screens for cardiovascular drug discovery.

We are also applying unbiased screening approaches to identify novel therapeutic candidates for cardiac regeneration in human cardiac organoids.

Current projects

Targeted direct reprogramming of adult cardiac fibroblasts to functional cardiomyocytes

2016-2018, NHMRC Project Grant, Collaboration: Prof Justin Cooper-White, Dr Enzo Porrello, Prof Ernst Wolvetang
 

Examining an extracellular matrix regulator required for cardiovascular development

2016-2019, NHMRC Project Grant, Collaboration: Dr Kelly Smith, Dr Mathias Francois, AProf Carol Wicking, Dr Enzo Porrello, Dr Ben Hogan
 

Regulation of endogenous heart regeneration by an anti-fibrotic microRNA

2015-2017, NHMRC Project Grant, Dr Enzo Porello, Dr James Hudson
 

Regulation of heart development and regeneration by DNA methylation

2015-2017, NHMRC Project Grant, Dr Enzo Porello, Dr James Hudson
 

Discovery of novel heart failure therapeutics via development of a next generation therapeutic screening platform: Force-generating human heart tissue micro-arrays

2014-2016, NHMRC Project Grant, Dr James Hudson

Recently completed projects

Chemosensory receptors in heart

2012-2015, National Heart Foundation of Australia

 

Uncovering the role of genomic dark matter in heart development and regeneration

2014-2015, UQ Foundation Research Excellence Awards - DVC(R) Funding

Head of laboratory

Staff

Students

Original articles

Titmarsh D, Glass N, Mills R, Hidalgo A, Wolvetang E, Porrello EHudson J, Cooper-White J. Induction of Human iPSC-Derived Cardiomyocyte Proliferation Revealed by Combinatorial Screening in High Density Microbioreactor Arrays. Scientific Reports 2016 Epub ahead of print.

 

Foster SR, Porrello ER, Stefani M, Smith NJ, Molenaar P, dos Remedios CG, Thomas WG, Ramialison M. Cardiac gene expression data and in silico analysis provide novel insights into human and mouse taste receptor gene regulation. NSAP 2015 388(10):1009-27.

 

Sim CB, Ziemann M, Kaspi A, Harikrishnan KN, Ooi J, Khurana I, Chang L, Hudson JE, El-Osta A, Porrello ER. Dynamic changes in the cardiac methylome during postnatal development. FASEB Journal 2015 29(4):1329-1343.

 

Ovchinnikov DA, Hidalgo A, Yang S-K, Zhang X, Hudson J, Mazzone SB, Chen C, Cooper-White JJ, and Wolvetang EJ. Isolation of Contractile Cardiomyocytes from Human Pluripotent Stem-Cell-Derived Cardiomyogenic Cultures Using a Human NCX1-EGFP Reporter. Stem Cells Dev 2015 24(1):11-20.

 

Morrison JL, Zhang S, Tellam RL, Brooks DA, McMillen IC, Porrello ER, Botting KJ. Regulation of microRNA during cardiomyocyte maturation in sheep. BMC Genomics 2015 16:541.

 

Bernardo BC, Nguyen SS, Winbanks CE, Gao XM, Boey EJH, Tham YK, Kiriazis H, Ooi JYY, Porrello ER, Igoor S, Thomas CJ, Gregorevic P, Lin RCY, Du XJ, McMullen JR. Therapeutic silencing of miR-652 restores heart function and attenuates adverse remodeling in a setting of established pathological hypertrophy. FASEB J 2014 28(12):5097-110.

 

Mahmoud AI, Porrello ER, Kimura W, Olson EN, Sadek HA. Surgical models of cardiac injury in neonatal mice. Nature Protocols 2014 9(2):305-11.

 

Aurora AB, Porrello ER, Tan W, Mahmoud AI, Hill JA, Bassel-Duby R, Sadek HA, Olson EN. Macrophages are required for neonatal heart regeneration. J Clin Invest 2014 124(3):1382-92.

 

Xin M, Kim Y, Sutherland LB, Murakami M, Qi X, McAnally J, Porrello ER, Mahmoud AI, Tan W, Shelton JM, Richardson JA, Sadek HA, Bassel-Duby R, Olson EN. Hippo pathway effector Yap promotes cardiac regeneration. Proc Natl Acad Sci USA 2013 110(34): 13839-44.

 

Mahmoud AI, Kocabas, F, Muralidhar S, Kimura W, Koura AS, Thet S, Porrello ER, Sadek HA. Meis1 regulates post-natal cardiomyocyte cell cycle arrest. Nature 2013 497(7448): 249-53.

 

Porrello ER, Mahmoud AI, Simpson E, Johnson BA, Grinsfelder D, Canseco D, Mammen PP, Rothermel BA, Olson EN, Sadek HA. Regulation of neonatal and adult heart regeneration by the miR-15 family. Proc Natl Acad Sci USA 2013 110(1): 187-92.

 

Foster S, Porrello ER, Purdue B, Chan HW, Voigt A, Frenzel S, Hannan RD, Moritz KM, Simmons DG, Roura E, Boehm U, Meyerhof W, Thomas WG. Expression, regulation and putative nutrient sensing function of taste GPCRs in the heart. PLoS One 2013 8(5): e64579.

 

Titmarsh DM, Hudson JE, Hidalgo A, Elefanty A, Stanley EG, Wolvetang EJ, Cooper-White JJ. Microbioreactor Arrays for Full Factorial Screening of Exogenous and Paracrine Factors in Human Embryonic Stem Cell Differentiation. PLoS ONE 2012 7(12): e52405.

 

Hudson JE, Titmarsh DM, Hildago A, Wolvetang EJ, Cooper-White JJ. Primitive Cardiac Cells from Human Embryonic Stem Cells. Stem Cells Dev 2012 10; 21(9):1513-23.

 

Kocabas F, Mahmoud AI, Sosic D, Porrello ER, Chen R, Garcia J, Deberardinis R, Sadek HA. The hypoxic epicardial and subepicardial microenvironment. Journal of Cardiovascular Translational Research 2012 5(5): 654-65.

 

Frith JE, Mills RJ, Hudson JE, Cooper-White JJ. Tailored Integrin-Extracellular Matrix Interactions to Direct Human Mesenchymal Stem Cell Differentiation. Stem Cells and Development 2012 21(13):2442-56.

 

Hudson JE, Brooke G, Blair C, Wolvetang EJ, Cooper-White JJ. Development of Myocardial Constructs Using Modulus-Matched Acrylated Polypropylene Glycol Triol (aPPGT) Substrate and Different Non-Myocyte Cell Populations. Tissue Eng Part A 2011 17(17-18):2279-89.

 

Mills RJ, Frith JE, Hudson JE, Cooper-White JJ. Effect of geometric challenges on cell migration. Tissue Eng Part C 2011 17(10):999-1010.

 

Porrello ER, Mahmoud AI, Simpson E, Hill JA Richardson JA, Olson EN, Sadek H. Transient regenerative potential of the neonatal mouse heart. Science 2011 331(6020): 1078-80.

 

Hudson JEMills RJ, Frith JE, Brooke G, Jaramillo-Ferrada P, Wolvetang EJ, Cooper-White JJ. A defined medium and substrate for expansion of human mesenchymal stromal cell progenitors that enriches for osteo- and chondro-genic precursors. Stem Cells Dev 2011 20(1):77-87.

 

Porrello ER, Johnson BA, Aurora AB, Simpson E, Nam Y-J, Matkovich SJ, Dorn GW, van Rooij E, Olson EN. miR-15 family regulates postnatal mitotic arrest of cardiomyocytes. Circulation Research 2011 109(6): 670-9.

 

O’Callaghan EL, Dosanjh J, Porrello ER, Delbridge LM, Thomas WG, Allen AM. Regulation of angiotensinogen by angiotensin II in mouse primary astrocyte cultures. Journal of Neurochemistry 2011 119(1): 18-26.

 

Porrello ER1, Pfleger KD, Seeber RM, Qian H, Oro C, Abogadie F, Delbridge LM, Thomas WG. Heteromerization of angiotensin receptors changes trafficking and arrestin recruitment profiles. Cellular Signalling 2011 23(11): 1767-76. 1Co-corresponding author

 

Porrello ER, Meeker WF, Thomas WG, Widdop RE, Delbridge LMD. Glucocorticoids are antihypertrophic in neonatal cardiomyocytes co-expressing AT1 and AT2 angiotensin receptors. Neonatology 2010 97(3):257-265.

 

Gezmish O, Tare M, Parkington HC, Morley R, Porrello ER, Bubb KJ, Black MJ. Maternal vitamin D deficiency leads to cardiac hypertrophy in rat offspring. Reproductive Science 2010 17(2):168-76.

 

Hudson JE, Frith JE, Donose BC, Rondeau E, Mills RJ, Wolvetang EJ, Brooke G, Cooper-White JJ. A synthetic elastomer based on acrylated polypropylene glycol triol with tunable modulus for tissue engineering applications. Biomaterials 2010 31:7937-7947.

 

Markway BD, Tan G-K, Brooke G, Hudson JE, Cooper-White JJ, Doran MR. Enhanced Chondrogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells in Low Oxygen Environment Micropellet Cultures. Cell Transplantation 2010 19(1):29-42.

 

Porrello ER, D'Amore A, Curl CL, Allen AM, Harrap SB, Thomas WG, Delbridge LMD. Angiotensin II type 2 receptor antagonizes angiotensin II type 1 receptor-mediated cardiomyocyte autophagy. Hypertension 2009.53(6):1032-40.

 

Porrello ER, Bell JR, Schertzer JD, Curl CL, McMullen JR, Mellor KM, Ritchie RH, Allen AM, Lynch GS, Harrap SB, Thomas WG, Delbridge LMD. Heritable pathologic cardiac hypertrophy in adulthood is preceded by neonatal cardiac growth restriction. American Journal of Physiology (Regulatory, Integrative and Comparative Physiology) 2009 296(3):R672-680.

 

Bell JR, Porrello ER, Huggins CE, Harrap SB, Delbridge LMD. The intrinsic resistance of female hearts to an ischemic insult is abrogated in primary cardiac hypertrophy. American Journal of Physiology (Heart, Lung, and Circulatory) 2008 294(4): H1514-22.

 

Porrello ER, Huggins CE, Curl CL, Domenighetti AA, Pedrazzini T, Delbridge LMD, Morgan TO. Elevated dietary sodium intake exacerbates myocardial hypertrophy associated with cardiac-specific overproduction of angiotensin II. Journal of the Renin-Angiotensin-Aldosterone System 2004 5(4): 169-75.

 

Reviews and book chapters

Quaife-Ryan GA, Sim CB, Porrello ER*Hudson JE*. Resetting the epigenome for heart regeneration. Seminars in Cell and Developmental Biology. 2016 Epub ahead of print.

 

Porrello ER, Olson EN. A neonatal blueprint for cardiac regeneration. Stem Cell Res 2014 13(3 Pt B):556-70.

 

Frith JE, Porrello ER, Cooper-White JJ. New frontiers in microRNA-based tissue regeneration. Stem Cells Transl Med 2014 3(8):969-76.

 

Hudson JE, Porrello ER. The noncoding road towards cardiac regeneration. Journal of Cardiovascular Translational Research 2013 6(6):909-23.

 

Porrello ER. MicroRNAs in cardiac development and regeneration. 2013 Clinical Science 2013. 125(4): 151-166.

 

Christalla P*, Hudson JE*, Zimmermann W-H. The Cardiogenic Niche as Fundamental Building Block of Engineered Myocardium. Cells Tissues Organs 2012 195(1-2):82-93. *Authors contributed equally

 

Mahmoud AI, Porrello ER. Turning back the cardiac regenerative clock: lessons from the neonate. Trends in Cardiovascular Medicine 2012 22(5):128-133.

 

Hudson JE, Christalla P, Zimmermann, W-H. Pluripotent Stem Cell-Derived Cardiomyocytes for Industrial and Clinical Applications. 2012. Modern Biopharmaceuticals, Recent Success Stories. Wiley-VCH Verlag GmbH & Co. KGaA 2013.

 

Hudson JE, Zimmermann W-H. Tuning Wnt-signaling to enhance cardiomyogenesis in human embryonic and induced pluripotent stem cells. J Mol Cell Cardiol 2011 51(3):277-9.

 

Frith JE*, Hudson JE*, Cooper-White JJ. Tissue engineering and regenerative medicine international society - Asia Pacific (TERMIS-AP) meeting 2010. Regen Med. 2011;6:167-170. *Authors contributed equally

 

Rowlands A, Hudson JE, Cooper-White JJ. From scrawny to brawny: the quest for neomusculogenesis; smart surfaces and scaffolds for muscle tissue engineering. Expert Rev Med Devices. 2007;4:709-728.

 

Porrello ER, Olson EN. Building a new heart from old parts: stem cell turnover in the aging heart. Circulation Research 2010 107(11): 1292-4.

 

Porrello ER, Delbridge LM. Cardiomyocyte autophagy is regulated by angiotensin II type 1 and 2 receptors. Autophagy 2009 5(8):1215-6.

 

Porrello ER1, Delbridge LMD, Thomas WG. The angiotensin II type 2 (AT2) receptor: an enigmatic seven transmembrane receptor. Frontiers in Bioscience 2009 14:958-972. 1Co-corresponding author

 

Porrello ER, Widdop RE, Delbridge LMD. Early origins of cardiac hypertrophy: does cardiomyocyte attrition program for pathological ‘catch-up’ growth of the heart? Clinical and Experimental Pharmacology and Physiology 2008 35:1358-1364.

Patents

1. Mills RM, Titmarsh DM, Porrello ER, Hudson JE. 2016. Cardiac Maturation. Provisional filing PAT-02238.

A screening device and conditions to promote maturation of human cardiac organoids.

 

2. Quaife-Ryan, GA, Hudson JE, Porrello ER. 2016, Cardiac regeneration. Provisional filing PAT-02255.

A therapy to induce cardiac regeneration.

 

3. Tiburcy M, Hudson JE, Zimmermann W.-H., 2013. Method for producing Engineered Heart Muscle (EHM) - EP13181352.9

Method for producing defined, serum-free, human cardiac organoids.

 

4. Hudson JE, Tiburcy M, Zimmermann W.-H., 2013. A method to direct differentiation of pluripotent stem cells into functional heart muscle - EP13185344.2

Method for directing differentiation to produce defined, serum-free, human cardiac organoids.

 

Justin Cooper-White
Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, AUSTRALIA

David A. Elliott
Cardiac Development Laboratory, Cell Biology Theme, Murdoch Childrens Research Institute, Melbourne, AUSTRALIA

Assam El-Osta
Baker IDI Heart and Diabetes Institute, Melboune, AUSTRALIA

Mat Francois
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, Brisbane, AUSTRALIA

Paul Gregorevic
Baker IDI Heart and Diabetes Institute, Melboune, AUSTRALIA

Richard Harvey
Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, AUSTRALIA

Ben Hogan
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, Brisbane, AUSTRALIA

Rob Parton
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland, Brisbane, AUSTRALIA

Bradley Launikonis
School of Biomedical Sciences (SBMS), The University of Queensland, Brisbane, AUSTRALIA

Stuart Mazzone
School of Biomedical Sciences (SBMS), The University of Queensland, Brisbane, AUSTRALIA

Kelly Smith
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, Brisbane, AUSTRALIA

Walter Thomas
School of Biomedical Sciences (SBMS), The University of Queensland, Brisbane, AUSTRALIA

Peter Thorn
School of Biomedical Sciences (SBMS), The University of Queensland, Brisbane, AUSTRALIA

Carol Wicking
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, Brisbane, AUSTRALIA

Ernst Wolvetang
Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, AUSTRALIA

  • Development of new heart failure therapeutics by analysing signalling heart failure as a network

2014-2017, Early Career Fellowship, Peter Doherty Australian Biomedical Fellowship, NHMRC - James Hudson

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