Introduction

The RCH vascular anomalies multidisciplinary team has a strong commitment to research.  Our aim is to understand the impact of vascular anomalies on the lives of children and young adults and to be at the cutting edge of implementation of new treatments for vascular anomalies.

We have a number of strong collaborations with researchers in Melbourne and around the world.  Our strongest link is to the Murdoch Children’s Research Institute where Prof. Penington is a Group Leader and many members of the team have appointments.   In the laboratory our aim is to better understand the biology of vascular malformations and how this can lead to new treatments. The laboratory is strongly focused on genetic and cell biology studies that could tell the patients how a specific vascular anomaly has developed and what is the future for new treatment options. We are collaborating with Dr. Wayne Phillips and his team at the Peter MacCallum Cancer Institute to better understand how changes in the genes within a vascular malformation lead to symptoms.

In addition, our laboratory is involved in a number of clinical research projects aimed at more precisely defining unknown diagnoses and understanding how treatments affect the lives of patients with vascular anomalies.   We have a strong interest in quantifying the effects of vascular anomalies on quality of life and conducting studies that can answer patient’s concerns such as ‘why is propranolol not effective for my child’s haemangioma?’ or ‘why do we use certain wound dressings to treat infantile haemangioma ulcers?’

Our team

Prof Tony Penington is a group leader in the Vascular Biology Research Laboratory. He completed his medical degree in 1985 and his surgical training in 1995. He was awarded an MD degree by the University of Melbourne in 2008 and became the Jigsaw professor of Plastic and Reconstructive Surgery in 2012. In addition to his busy clinical practice, Tony has a strong research interest in vascular anomalies and leads a clinical research program aimed at improving plastic surgery practice ensuring our patients receive the highest level of care.

A/Prof Rod Philips is a paediatric skin specialist and a clinical researcher. He is a co-ordinator of the Royal Children's Hospital Vascular Anomalies Centre. Rod has greatly contributed to our understanding of propranolol effect in treatment of infantile haemangioma. He actively participates in the vascular biology laboratory discussions and project development.

Jodie Simpson is the nurse coordinator in the vascular anomalies service, and participates in a range of research projects across the vascular anomalies service, especially in quantifying effects on quality of life.

Nerida Sleebs is a research scientist who works in the stem cell laboratory in the Murdoch Children’s Research Institute.  She is highly skilled in a range of basic laboratory techniques and has significant experience in the isolation and growth of cells from vascular anomalies in tissue culture.

Dr Zerina Lokmic is a scientist and nurse educator in the Department of Nursing at the University of Melbourne.  She received her doctorate in biomedicine in 2005 from the University of Melbourne’s Department of Surgery and trained as a post-doctoral research fellow at the Institute for Physiological Chemistry and Pathobiochemistry at the University of Munster, Germany. Zerina is active in a number of clinical research projects and strives to improve clinical practice and policy development aimed at improving health outcomes of children with vascular anomalies.

How can I support research?

We welcome your participation in our research. For many of the laboratory-based research projects you can contribute by donating tissue samples at the time of surgery that would otherwise be discarded. At the time of consultation, you may be asked if you wish to participate in an ethically-approved research study. If you are willing to contribute, you will be asked to read a consent form and sign it in the presence of a person who is not involved in your clinical management.

We encourage you to visit this page and examine the research projects available and contact us if you wish to participate in any of the research projects. For some projects you may receive a letter inviting you to participate in some way. We are also keen to hear from you if you have any specific questions that you may need answered but that at the moment we have no information about. Such questions can become a research topic that would help vascular anomalies patients around the world.

Current biomedical research projects:

Project I: Differentiation of induced pluripotential stem cells into endothelial cells.
Prof Tony Penington, Nerida Sleebs, Andrew Elefanty

Understanding the earliest events in development of vascular structures in the embryo will help us understand how vascular malformations develop and are sustained in the human body.  By inducing pluripotent stem cells which carry the mutations known to cause vascular malformations into endothelial cells, the governing cells of the vascular system, we hope to understand how these mutations cause the abnormal anatomy seen in vascular malformation, discover new avenues of treatment and develop a test bed for new drug treatments. 

Project II: The biology of lymphatic malformations
Prof Tony Penington, Nerida Sleebs, Dr Zerina Lokmic,

Our research aims to identify and understand cause and consequence of lymphatic malformations.  To do this we isolate from tissue removed at surgery, the endothelial cells, the cyst lining cells which we believe are altered in this condition.  We grow and study these cells in the laboratory.  We hope to understand how lymphatic malformations develop and identify specific molecules that might be the targets of future drug treatments.

Clinical research projects:

We will post many of our clinical research projects on our webpage where we will ask you to contact us if you think that you can help us with these projects. Many of them will involve short on-line surveys or interviews. With each project we will endeavour to make it as convenient as possible for you.

Quality of Life in patients with vascular anomalies.
Prof. Tony Penington, Jodie Simpson, A/Prof Rod Phillips.

The effects of a vascular malformation on quality of life can be profound, but unless we learn to measure these effects it will be difficult to quantify the beneficial effects of any treatment. We also need this knowledge to put the case to government funding bodies to fund access to new treatments as they become available. Along with the team at Curve Tomorrow we are developing innovative new ways to electronically deliver quality of life health questionnaires to patients which will allow us to map the effects of vascular anomalies on quality of life over time.  We are also working with Curve Tomorrow to develop ways to use information technology to improve the way we communicate with patients about treatment.

Atenolol as a treatment for haemangioma of infancy.
AProf. Rod Phillips, Jodie Simpson

Propranolol is an effective treatment for haemangioma of infancy and while it is well tolerated, there are occasional side effects.  We are evaluating the effectiveness of the drug Atenolol as an alternative treatment.  In the future we hope to be able to begin clinical trials with other agents to replace or enhance the effectiveness of propranolol.

Ultrasound misdiagnosis of haemangioma of infancy
Prof Tony Penington, AProf Rod Phillips, Jodie Simpson

Haemangioma of infancy is the most common tumour of childhood and is usually relatively easy to diagnose clinically.  A number of patients with haemangioma present to our service with ultrasound reports indicating incorrectly that they have a condition called ‘AVM’, a much rarer and more serious diagnosis. We wish to understand why this occurs and educate community radiologists about the distressing effect an incorrect diagnosis like this can have on parents. 

Selected publications:

• Lokmic, Z., Mitchell GM, Koh, N, Bastiaanse J, Gerrand Y-W, Williams, E.D. Penington A.J. Isolation of human lymphatic malformation endothelial cells, their in vitro characterization and in vivo survival in a mouse xenograft model. Angiogenesis, 2014;17(1):1-15
• Phillips R, Lokmic Z, Crock C, Penington A. Failed treatment of ulcerated haemangiomas. Archives of Disease in Childhood, 2014;50(8):619-25.
• Phillips RJ, Penington AJ, Bekhor PS, Crock CM. Use of propranolol for treatment of infantile haemangiomas in an outpatient setting. J Paediatr Child Health. 2012 Oct;48(10):902-6.
• Phillips R et al    Infantile haemangiomas that failed treatment with propranolol: clinical and histopathological features. (2014)   Journal of Paediatrics and Child Health 50 (8) 619-25.
• Smithson, Sarah; Rademaker, Marius;… Penington A…Phillips RJ.  Consensus Statement for the Treatment of Infantile Haemangiomas with Propranolol.  (2017) Australasian Journal of Dermatology 58 (2): 155-159.
• Soblet, J., Kangas, J., Nätynki, M.,  Mendola, A., Helaers, R., Uebelhoer, M., Kaakinen, M., Cordisco, M., Dompmartin, A., Enjolras, O., Holden, S., Irvine, A.D., Kangesu, L., Léauté-Labrèze, C., Lanoel, C., Lokmic, Z., Maas, S., McAleer, M.A., Penington, A., Rieu, P., Syed, S van der Vleuten, C., Watson,R.,  Fishman, S.J.,  Mulliken, J.B., Eklund, L. Limaye, N., Boon, L.M., Vikkula, M. (2017)  Blue Rubber Bleb Nevus (BRBN) Syndrome is caused by Somatic TEK (TIE2) Mutations. J Invest Dermatol. 137(1): 207-216.
• Roderic J Phillips; Catherine M Crock; Anthony J Penington; Philip S Bekhor , Title: Prolonged tumour growth after treatment of infantile haemangioma with propranolol.  Medical Journal of Aust 2017; 206 (3):
• Muggli, Evelyne (MPH); Matthews, Harold (BPsych(Hons)); Penington, Anthony (MDBS); Claes, Peter (PhD); O’Leary, Colleen (PhD); Forster, Della (PhD); Donath, Susan (MA); Anderson, Peter J. (PhD); Lewis, Sharon (PhD); Nagle, Cate (PhD); Craig, Jeffrey M. (PhD); White, Susan M. (MBBS); Elliott, Elizabeth J. MD; Halliday, Jane (PhD).  (2017) Association between Prenatal Alcohol Exposure and Craniofacial Shape of Children at 12 Months of Age.  JAMA Paediatrics – American Medical Association   171(8): 771-80
• Lockmic, Z; Hallenstein, L; Penington, AJ   Title: Parental Experience of Prenatal Diagnosis of Lymphatic Malformation.   Journal Lymphology 50 (2017) 16-26
• Kaderbhai, J; Heggie, A; Breik, O; Penington, AJ   Title: High-flow paediatric mandibular arteriovenous malformations: case reports and a review of current management  (2017) International Journal of Oral & Maxillofacial Surgery 46(12): 1650-1655.
• Wagner K, Lokmic Z, Penington AJ  Prolonged antibiotic treatment for low flow vascular malformations (2018) Journal of Pediatric Surgery 53(4): 798 – 801.
• Lokmic Z, Grainger T, Ataputtu NV, Phillips RJ & Penington AJ.  Wound management of ulcerated haemangioma of infancy – an audit.  (2017) International Wound Journal 14(6): 967-72.
• Horbach, S E R; van der Horst, C M A M; Blei, F; van der Vleuten, C J M; Frieden, I J; Richter, G T; Tan, S T; Muir, T; Penington A; Boon, L M.and the OVAMA consensus group (2018)  Development of an international core outcome set for peripheral vascular malformations (OVAMA project). The British Journal of Dermatology 178(2): 473-81
• Fan Y, Matthews H, Kilpatrick N, Claes P, Clement J & Penington A  (2018)  Facial morphology and growth following surgery for congenital midline cervical cleft patients International Journal of Oral and Maxillofacial Surgery 47(4): 437-441
• Matthews HS, Penington AJ, Hardiman R, Fan Y, Clement JG, Kilpatrick NM, Claes PD   (2018)  Modelling 3D craniofacial growth trajectories for population comparison and classification illustrated using sex-differences.  Scientific Reports 8:11 4771
• Notini Lauren, Gillam Lynn, Spriggs Merle, Penington Anthony (2019)  ‘Operating is the easy part’: Surgeons’ decision-making processes and responses to parental requests for elective paediatric appearance-altering surgery.  Journal of Plastic Reconstructive and Aesthetic Surgery 72 (8): 1379-87.
• Bastiaanse J, Lokmic Z, Williams RA, Penington AJ: Sympathetic innervation of glomus tumours. Plastic and Reconstructive Surgery 2013 Dec;132(6):1088e-91e2013.
• Lokmic, Z and Mitchell GM. Visualisation and stereological assessment of blood and lymphatic vessels. Histol Histopathol. 2011 Jun;26 (6):781-96.

Funding:

We have been fortunate to receive funding from the Jigsaw Foundation, The Baker Foundation, The Royal Children’s Hospital Foundation, The Ian Potter Foundation and the National Health and Medical Research Council.

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