Cardiac Development and Disease
Head of Laboratory
Dr David Pennisi
Otto Hirschfeld Building (#81), Room 715, St Lucia Campus
Han Sheng Chiu, Research Assistant
- Swati Iyer, PhD student
- Richard Wang, Honours student
Congenital heart disease is the most common birth defect and encompasses a variety of developmental defects, including Tetralogy of Fallot and malformation of the septa, valves and coronary vessels. Currently, the molecular and genetic processes that go awry during heart development remain largely unknown. In addition, coronary artery disease commonly manifests as heart attack and angina, resulting in damaged myocardium that cannot be regenerated by the body.
Currently there are no adequate cellular or molecular therapies for coronary artery disease. Any future clinical or therapeutical interventions aimed at revascularisation of an ischemic heart, or regeneration of damaged coronary vessels, requires a clear understanding of the molecular and genetic programmes that are in place in the embryo. A greater understanding of heart development will also be necessary to provide the basis for biologically engineered heart tissues.
Dr Pennisis research group is exploring the molecular and genetic basis of heart development during embryogenesis. This understanding will be key to developing future potential molecular and cellular therapeutic interventions. We use genetically engineered mouse models and state-of-the-art molecular and imaging techniques to understand the role of growth factor signalling pathways in key processes during heart development.
Some of the processes we study include:
- Formation of the coronary vasculature;
- Interactions between the epicardium and the myocardium;
- The role of growth factor signalling in heart development and disease.
- Chiu, H. S., York, J. P., Wilkinson, L., Zhang, P., Little, M. H., Pennisi, D. J.* (2012). Production of a mouse line with a conditional Crim1 Mutant Allele. Genesis. 50: 711716.
- Pennisi, D.*, Chiu, H. S., Kinna, G., Wilkinson, L., Simmons, D., Little, M. (2012). Crim1 has an essential role in glycogen trophoblast cell and sinusoidal trophoblast giant cell development in the placenta. Placenta. 33: 175182.
- Little, M. H., Georgas, K., Pennisi, D. J., and Wilkinson, L. (2010). Kidney development: two tales of tubulogenesis. Current Topics in Developmental Biology. 90: 193229.
- Pennisi, D. J.* and Mikawa, T. (2009). FGFR-1 is required by epicardium-derived cells for myocardial invasion and correct coronary vascular lineage differentiation. Developmental Biology. 328: 148159.
- Wilkinson, L., Gilbert, T., Sipos, A., Toma, I., Pennisi, D. J., Peti-Peterdi, J., and Little, M. H. (2009). Loss of renal microvascular integrity in postnatal Crim1 hypomorphic transgenic mice. Kidney International. 76: 11611171.
- Pennisi, D. J., Wilkinson, L., Kolle, G., Sohaskey, M. L., Gillider, K., Piper, M. J., McAvoy, J. W., Lovicu, F. J., and Little, M. H. (2007). Crim1KST264/KST264 mice display a disruption of the Crim1 gene resulting in perinatal lethality with defects in multiple organ systems. Developmental Dynamics. 236: 502511.
- Wilkinson, L., Gilbert, T., Kinna, G., Ruta, L. A., Pennisi, D. J., Kett, M., and Little, M. H. (2007). Crim1KST264/KST264 mice implicate Crim1 in the regulation of vascular endothelial growth factor-A activity during glomerular vascular development. Journal of the American Society of Nephrology. 18: 16971708.
- Pennisi, D. J., and Mikawa, T. (2005). Normal patterning of the coronary capillary plexus is dependent on the correct transmural gradient of FGF expression in the myocardium. Developmental Biology. 279: 378390.
- The role of adhesion, migration and invasion of epicardial cells in the formation of the coronary vasculature.
- Assessing cardiovascular function in adult mice with engineered mutations using magnetic resonance imaging (MRI). (in collaboration with the Centre for Advanced Imaging, UQ)
- Investigating the role of hypoxia in patterning the coronary blood vessels during embryogenesis.
- Characterisation of the stem cells (colony forming unit-fibroblasts) from the hearts of mice.
- Understanding formation of the coronary blood vessels using genetically engineered mice.
- Assessing cardiac function, injury and repair in adult cardiac stem cell-depleted mouse models.
The Pennisi group also has research projects available for undergraduate (SCIE3220/SCIE3221) and Advanced Study Program in Science students, incorporating a range of molecular, cell biological, embryological, and whole-animal studies, based on the above themes.
- NHMRC Project Grant, The Role of Crim1 in Cardiovascular Development (ID: 631658)
- UQ New Staff Research Start-Up Grant, Crim1 in Coronary Blood Vessel Development