Newcastle University

Research Interests

Physical and genetic aspects of cardiac morphogenesis

My research programme is closely related and complementary to that of Professor Deborah Henderson. Our research addresses the genetic and, in the widest non-genetic sense, epigenetic mechanisms that regulate normal cardiac development which when disturbed can produce congenital structural heart disease or influence the response of adult myocardium to disease.

We are particularly interested in the role of the Wnt signalling network in shaping the developing heart and I am extending Deb’s work in planar cell polarity signalling to canonical and calcium Wnt signalling. Over the last 5 years I have led the development of several laboratory models that also complement our mouse genetics expertise, including zebrafish and an embryonic stem cell model of cardiogenesis. Recently, we have begun to analyse and confirm our findings in human material and are developing in silico imaging techniques. Both Deb and I are interested in environmental influences and are investigating how agents such as folic acid, anthracyclines and alcohol, may affect morphogenesis. We are also investigating the reactivation of our embryonic developmental pathways in the regenerating heart. We are investigating the adult zebrafish heart, which following surgical removal of the ventricular apex, has the capacity to fully regenerate without scarring.

In our quest to understand heart development I have taken an engineering approach to morphogenesis which complements Deb Henderson’s genetic analysis. In the first steps of this long-term project I am looking at how we can quantify passive and active mechanical properties of the forming heart on three different orders of scale. At a cellular level we have established cell force traction microscopy and are extending the model by attempting to integrate cell attachment and cytoskeletal data to characterise the force loading of structural elements within cells that form the heart, for example primary and second heart field cardiomyocytes, neural crest cells, endothelial cells and fibroblasts. This work has lead to collaborations with biomechanical engineers based both in Europe and the UK. At the tissue level of organisation we are using embryo slice culture to follow cells within their natural environment. Finally, at an organ/system level we are seeking to analyse the global function of the embryonic cardiovascular system, using the zebrafish as an accessible model - before progressing to more complex systems. Hence, throughout our research we are seeking to collect meaningful data that can be quantified and then used to create and test in silico model systems.

Co-workers

Robert Anderson BSc, MD, FRCPath, FESC, FECTS
Visiting Professor
Alina Andras, BSC, PhD
Newcastle Hospitals Trust JRE Research Associate
Veronica Boczonadi BSc, MSc
BHF Research Associate
David Burns
Zebrafish Aquarium technician
Nicholas Child MB BS MRCP
BHF Clinical Research Training Fellow
Deborah Henderson BSc PhD
Professor of Cardiac Development, BHF Basic Science Lecturer
Darren Hoyland BSc, PhD
BHF Research Assistant
Tania Papoutsi BSc
BHF PhD Student
Helen Phillips BSc, PhD
Newcastle University Faculty of Medical Sciences Fellow
Hong Jun Rhee BSc, PhD
BHF Research Associate

• Phillips HM, Hildreth V, Peat JD, Murdoch JN, Kobayashi K, Chaudhry B, Henderson DJ. Non-cell-autonomous roles for the planar cell polarity gene vangl2 in development of the coronary circulation. Circulation Research 2008, 102(5), 615-623.
• Phillips HM, Rhee HJ, Murdoch JN, Hildreth V, Peat JD, Anderson RH, Copp AJ, Chaudhry B, Henderson DJ. Disruption of planar cell polarity signaling results in congenital heart defects and cardiomyopathy attributable to early cardiomyocyte disorganization. Circulation Research 2007, 101(2), 137-145.
• Phillips HM, Murdoch JN, Chaudhry B, Copp AJ, Henderson DJ. Vangl2 acts via RhoA signaling to regulate polarized cell movements during development of the proximal outflow tract. Circulation Research 2005, 96(3), 292-299.
• Henderson DJ, Phillips HM, Chaudhry B. Vang-like 2 and noncanonical Wnt signaling in outflow tract development. Trends in Cardiovascular Medicine 2006. , 16(2), 38-45.
• McKinney PA, Jones S, Parslow R, Davey N, Darowski M, Chaudhry B, Stack C, Parry G, Draper ES, PICANet Consent Study Grp. A feasibility study of signed consent for the collection of patient identifiable information for a national paediatric clinical audit database. British Medical Journal 2005, 330(7496), 877-879.
• Chaudhry B, Burns D, Henderson DJ. Cardiomyocyte aging: swimming against the clock. In: 2nd Congress of the European Society of Cardiology Council on Basic Cardiovascular Science: Frontiers in Cardiovascular Biology. 2012, London, UK: Oxford University Press.
• Henderson DJ, Boczonadi V, Humbert P, Chaudhry B. Conditional deletion of Scrib gene in the developing myocardium leads to congenital heart defects. In: 2nd Congress of the European Society of Cardiology Council on Basic Cardiovascular Science: Frontiers in Cardiovascular Biology. 2012, London, UK: Oxford University Press.
• Chaudhry B, Chrystal P, Henderson DJ. Fast Digital Laser Sheet Microscopy: swimaging in 6 dimensions. In: 2nd Congress of the European Society of Cardiology Council on Basic Cardiovascular Science: Frontiers in Cardiovascular Biology. 2012, London, UK: Oxford University Press.
• Anderson RH, Chaudhry B, Mohun TJ, Bamforth SD, Hoyland D, Phillips HM, Webb S, Moorman AF, Brown NA, Henderson DJ. Normal and abnormal development of the intrapericardial arterial trunks in man and mouse. Cardiovascular Research 2012, (epub ahead of print).
• Henderson DJ, Chaudhry B. Getting to the Heart of Planar Cell Polarity Signaling. Birth Defects Research Part A: Clinical and Molecular Teratology 2011, 91(6), 460-467.
• Simms RJ, Hynes AM, Eley L, Inglis D, Chaudhry B, Dawe HR, Sayer JA. Modelling a ciliopathy: ahi1 knockdown in model systems reveals an essential role in brain, retinal and renal development. Cellular and Molecular Life Sciences 2011, 69(6), 993-1009.
• Taylor JM, Saunter CD, Love GD, Girkin JM, Henderson DJ, Chaudhry B. Real-time optical gating for three-dimensional beating heart imaging. Journal of Biomedical Optics 2011, 16, 116021.
• Anderson RH, Cook A, Brown NA, Henderson DJ, Chaudhry B, Mohun T. Development of the outflow tracts with reference to aortopulmonary windows and aortoventricular tunnels. Cardiology in the Young 2010, 20(s3), 92-99.
• Hammond KL, Loynes HE, Mowbray C, Runke G, Hammerschmidt M, Mullins MC, Hildreth V, Chaudhry B, Whitfield TT. A Late Role for bmp2b in the Morphogenesis of Semicircular Canal Ducts in the Zebrafish Inner Ear. PLoS One 2009, 4(2), e4368.
• Bradshaw L, Chaudhry B, Hildreth V, Webb S, Henderson DJ. Dual role for neural crest cells during outflow tract septation in the neural crest-deficient mutant Splotch(2H). Journal of Anatomy 2009, 214(2), 245-257.
• Hildreth V, Webb S, Chaudhry B, Peat JD, Phillips HM, Brown N, Anderson RH, Henderson DJ. Left cardiac isomerism in the Sonic hedgehog null mouse. Journal of Anatomy 2009, 214(6), 894-904.
• Ioannides AS, Chaudhry B, Henderson DJ, Spitz L, Copp AJ. Dorsoventral patterning in oesophageal atresia with tracheo-oesophageal fistula: Evidence from a new mouse model. Journal of Pediatric Surgery 2002, 37(2), 185-191.
• Ng WF, Hernandez-Fuentes M, Baker R, Chaudhry A, Lechler RI. Reversibility with Interleukin-2 Suggests that T Cell Anergy Contributes to Donor-Specific Hyporesponsiveness in Renal Transplant Patients. Journal of the American Society of Nephrology 2002, 13(12), 2983-2989.
• Ng WF, Baker RJ, Hernandez-Fuentes M, Chaudhry A, Lechler RI. The role of T-cell anergy in the maintenance of donor-specific hyporesponsiveness in renal transplant recipients. Transplantation Proceedings 2001, 33(1-2), 154-155.