Prof Pia Ostergaard’s research focus mainly lies within lympho-vascular medicine.
The lymphatic system is important for fluid homeostasis but also has a critical immunological function, particularly with regard to infection. In addition, it plays a major role in cancer progression.
Lymphatic malformation or dysfunction can lead to Primary Lymphoedema, which is an inherited form of this disorder. Primary Lymphoedema is clinically and genetically heterogeneous and is caused by defects in the lymphatic system that lead to swelling of one or more limbs or other parts of the body. It is a rare disorder (1 in 6000) and in the more extreme forms can increase mortality, especially in infants.
Lymphoedema is a lifelong, often disabling condition associated with a high morbidity with distressing swelling of the affected limbs, recurrent cellulitis, discomfort and significant skin changes. Treatment is limited to compression garments and manual lymphatic drainage. Many patients find Primary Lymphoedema debilitating, embarrassing, stressful and painful leading to considerable psychological morbidity.
Prof Ostergaard’s research group has focused on the genetic causes of lymphatic failure. Seven genes have recently been identified by the group: EPHB4, GATA2, GJA1, GJC2, KIF11, PIEZO1, and VEGFC in seven clinically homogenous phenotypic sub-classifications of Primary Lymphoedema using exome sequencing techniques. Finding the genetic causes of lymphatic dysfunction in Primary Lymphoedema, increases our understanding of the development of the lymphatic system, and our results feed into the basic research on the lymphovascular system.
There still remain numerous Primary Lymphoedema patients where a genetic cause is yet to be identified. The identification of further disease causing genes is crucial in understanding the molecular pathways and mechanisms involved in disease pathogenesis, and will ultimately lead to the formation of novel and more effective treatments. Genetic advances in Primary Lymphoedema will also benefit patients through accurate molecular diagnosis.
Prof Ostergaard gained her PhD from the Natural History Museum and Imperial College London (2004) under the supervision of Professor GA Boxshall and Professor D Quicke.
Following a career break (2002-2005) to bring up children, Prof Ostergaard was appointed Daphne Jackson Fellow (part-time) at St George's, between 2005 and 2007. This was sponsored by the Daphne Jackson Trust and the Medical Research Council.
In 2007, Prof Ostergaard was appointed as a postdoctoral researcher at St George's, funded by the British Skin Foundation and the British Heart Foundation. Following this Prof Ostergaard was appointed as Lecturer in Human Genetics in 2013. Most recently, she has been promoted to Professor. Her research focus mainly lies within lymphovascular medicine.
For full list of publications, see Prof Ostergaard's Research Gate profile.
For reprints see the St George's Online Research Archive (SORA).
Key publications
Hägerling R, Van Zanten M, Behncke RY, Ulferts S, Hansmeier NR, Märkl B, et al. (2023). Erythematous capillary-lymphatic malformations mimicking blood vascular anomalies. JCI Insight. 8(20):e172179. doi: 10.1172/jci.insight.172179.
Mansour S, Josephs KS, Ostergaard P, Gordon K, Van Zanten M, Pearce J, et al. (2023). Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts. J Med Genet. 60(1):84-90. doi: 10.1136/jmedgenet-2021-107820.
Grigoriadis D, Sackey E, Riches K, van Zanten M, Brice G, England R, Mills M, Dobbins SE, et al. (2022) Investigation of clinical characteristics and genome associations in the 'UK Lipoedema' cohort. PLoS One. 17(10):e0274867. doi: 10.1371/journal.pone.0274867.
Martin-Almedina, S; Mortimer, P; Ostergaard, P (2021) Development and Physiological Functions of the Lymphatic System - Insights from Genetic Studies of Lymphedema. Physiol Rev, 101 (4). pp. 1809-1871. https://doi.org/10.1152/physrev.00006.2020
Martin-Almedina, S; Ogmen, K; Sackey, E; Grigoriadis, D; Karapouliou, C; Nadarajah, N; Ebbing, C; Lord, J; Mellis, R; Kortuem, F; et al. (2021) Janus-faced EPHB4-associated disorders: novel pathogenic variants and unreported intrafamilial overlapping phenotypes. Genet Med, 23 (7). pp. 1315-1324. https://doi.org/10.1038/s41436-021-01136-7
Gordon K, Varney R, Keeley V, et al. (2020) Update and audit of the St George's classification algorithm of primary lymphatic anomalies: a clinical and molecular approach to diagnosis. J Med Genet. jmedgenet-2019-106084. doi:10.1136/jmedgenet-2019-106084
Dempsey, E; Homfray, T; Simpson, JM; Jeffery, S; Mansour, S; Ostergaard, P (2020) Fetal hydrops – a review and a clinical approach to identifying the cause. Expert Opinion on Orphan Drugs, 8 (2-3). pp. 51-66. ISSN 2167-8707 https://doi.org/10.1080/21678707.2020.1719827
At St George's Hospital, Prof Ostergaard and colleagues have developed a nationwide lymphovascular clinical service with over 20 years of experience. The paediatric and primary lymphoedema clinic is a national tertiary referral service and has now collected DNA from over 1000 phenotyped cases of primary lymphoedema.
The Lymphovascular Research Group is a close collaboration between the clinicians and consultants in the St George's Hospital Primary Lymphoedema Clinic and a group of researchers in the Cardiovascular & Genomics Research Institute.