Lymphatic, adipose & regenerative medicine

Current research projects

• Understanding how lymphatic endothelial cells communicate with their microenvironment following soft tissue radiation injury with a focus on lymphoedema

  While radiation therapy is common in treatment of cancer patients, the consequences of RIBE in target tissues can cause severe side effects such as lymphoedema. We wish to understand this phenomenon at the cellular and genetic level by interrogating the effects that sub-lethal doses of radiation has on cells that comprise local tissue such as lymphatic and blood endothelial cells, fibroblasts, adipocytes, immune cells and adipose derived mesochymal stem cells. We have performed microarray analysis to obtain gene signatures of these cell types that are unique to the process of radiation injury and have established in vitro and in vivo lymphoedema and other injury models to interrogate the leading signalling pathways activated during this process. Our data has allowed us to explore novel mechanisms by which cells communicate during RIBE that will enable the design of novel therapeutics to target side effects of radiation injury such as tissue contracture, pain, lymphoedema and cardiac disease.

  Understanding the genetics in patients with radiation-injury induced lymphoedema

  It is estimated that approximately ~20% of women with breast cancer undergoing radiation and/or surgical resection of affected lymph nodes will develop lymphoedema. We would like to understand the genetic basis of these individuals and are in the process of a long-term genetic screen of patients that have begun to develop early signs of lymphoedema with the view of identifying any genes that are mutated.  This knowledge will assist in developing alternative treatment regimes and management of women with breast cancer, thereby preventing the onset of lymphoedema in those individuals genetically predisposed to developing secondary lymphoedema.

  Exploring the use adipose-derived stem cells (ADSCs) as a therapeutic agent in radiation induced injury

  It has been previously shown in plastic surgery that fat grafting has the ability to promote lymphangiogenesis in vitro and in vivo and ameliorate some of the chronic tissue effects of radiation injury. These effects are largely attributed to the presence of adipose-derived stem cells (ADSC) (Shukla et al., 2015). We wish to understand the mechanism by which ADSC confer their regenerative properties during radiation induced injury in local tissue. We have developed genetic, proteomics, metabolomics and cell function screens to understand what the key molecular components are critical for the process of ADSC rescue during radiation injury.

  Understanding the genetics of lipoedema, an alternative form of soft tissue swelling of the lower limbs

  Lipoedema is an alternative form of soft tissue swelling of the lower limbs, most common in females after the onset of puberty. Patients with lipoedema develop bilateral limb swelling secondary to adipose tissue deposits, with the feet generally spared (Rockson et al., 2000). Patients develop an immense amount of pain, bruising, immobility and can suffer from depression. There is some evidence to suggest that there is a lymphatic dysfunction component to this disease, however the link has not been clearly defined. There is very little, if any, literature pertaining to the genetics or mechanism of lipoedema and there are no current therapies. We are in the process of recruiting a large patient cohort to perform a genetic and tissue analysis of patients affected with lipoedema. We would like to understand the molecular basis of this disease with the view of developing therapeutic agents.