Associate Professor Anthony Ronald John Phillips

Profile Image
Associate Professor

Research | Current

The Applied Surgery and Metabolism Laboratory (ASML)

This laboratory was started when I joined resources with Dr Anthony Hickey (SBS) and Professor John Windsor (Dept of Surgery), to design and develop a novel environment specialised in fostering basic surgical research. This laboratory came to fruition in 2011 with the help of a Vice Chancellor Strategic Development Fund Award. It has now become a unique formal collaboration between the School of Biological Sciences (Faculty of Science) and Department of Surgery (Faculty of Medical and Health Sciences). One of its specific aims is to provide Trainee Surgeons and graduated medical doctors with a supportive place to do basic laboratory bench research surrounded by other surgeons doing research. But, it also has a ‘twist’, as the medical PhDs are also deliberately encouraged to work beside career science students also present in our laboratory and studying comparative physiology ie other animals (with my senior research colleague, Dr Anthony Hickey). This juxtaposition, of the study of surgery with investigation of nature’s other and sometimes unusual physiologies, is intended to provide cross fertilisation of ideas and techniques to stimulate an exciting new kind of surgical research environment. The ASML has direct links to the Department of Surgery and so we have the unique advantage of ready access to human tissue and clinical specimens for our studies. Our mandate is to prepare creative scientists and skilled academic surgeons for the future.

 

My research is divided into 5 major areas of investigation:

  1. Lymphatic fluid and its role in critical illness: This research is undertaken in collaboration with Professor John Windsor in the Department of Surgery. It is directed at developing an understanding of the role of ‘lymph mediated toxicity’ in how people’s organs fail in the Intensive Care Unit when they are critically ill (sepsis, inflammation and trauma). We think that lymphatic fluid arising from the intestine is involved in mediating the multiple organ failure that occurs in critical illness. Our lab focus is particularly on acute pancreatitis – (a disease characterised by inflammation of the pancreas and surrounding structures; often associated with Multiple Organ Dysfunction Syndrome (MODS); that in 20%-30% of cases can have a very severe clinical course or even death), as well as people with severe infections ( severe sepsis). We think lymph carries specific toxins from the gut to the heart and lungs that make them fail. We are using proteomic analysis (see Fig 1) and other analytical techniques on this fluid to determine the toxic moieties with the hope of devising new treatments to prevent organ failure by altering the composition of the toxic lymph (For a few relevant publications see {1-4}).

 

Figure1: The “Interactome” of the mesenteric lymph proteome after haemorrhagic shock (see Ref {3} below).

 

  1. Mitochondrial function and its role in critical illness: Mitochondria are small organelles in cells that are the main end-users of oxygen in the body and produce most of the cells energy (ATP). We are investigating the role of mitochondrial dysfunction in the multiple organ failure that occurs in critical illness. This research is undertaken jointly with Dr Anthony Hickey (ASML). Together we are looking to understand the nature of this dysfunction and to find biochemical ways of resuscitating cells at the mitochondrial level in the very sick. (For a few relevant publications see {5-7}).

 

  1. Non-coding RNA in surgical disease: In the cell there are parts of the DNA that do not encode proteins but still produce small pieces of RNA.  For a long time these had no clear function but are now known to significantly alter cellular function. These small RNA are very stable and can be found circulating in the blood. I work with Dr Cherie Blenkiron from the Department of Molecular Medicine and Pathology (FMHS) on this project and we are interested in their activity in cells and their role as clinical biomarkers for disease severity in critical illness. (For a few relevant publications see {8}).

 

  1. Wound healing and its treatment: I am also interested in the process of wound healing, both inside the body (abdominal organ healing after disease or surgery) and in the skin after trauma. I am involved in developing a wound healing product (Nexagon®) through my biotechnology industry work with CoDa Therapeutics Inc. (a “spin out” biotechnology company from the University of Auckland and University College, London). This drug now in clinical trials, works by modulating the way cells communicate with each other (gap junctions) with the effect of improving wound healing rates in hard to heal chronic wounds. (For a few relevant publications see {9-11}).

 

  1. Understanding the impact of fatty change in livers that will undergo resection or transplantation: I work part time for the Liver Transplant Service. The detrimental impact of a donor fatty liver on transplant outcome is known to be significant (slow recovery and poor function) and is a reason for substantial non-use of donor livers. Understanding this biology is important as society is undergoing an epidemic of obesity so many organ donors are now obese with a high incidence of fatty liver change. In a collaborative venture with Dr Anthony Hickey (ASML) and Dr Adam Bartlett (Surgeon from the New Zealand Liver Transplant Service and Dept of Surgery), we are investigating why transplanted and resected fatty liver performs poorly and how to offset these detrimental effects in order to improve organ use and surgical outcomes. (For a few relevant publications see {12-14}).

 

I also have several other active collaborative projects across the University over a wide range of other interests:

 

  1. Insect derived bioactives for surgery, especially from the medicinal maggot (with Dr Cherie Blenkiron and Prof John Windsor).
  2. Bacterial-Host communication in critical infective illness states (with Dr Simon Swift, Dr Cherie Blenkiron and A/P Cris Print, FMHS)
  3. Computational reconstruction of lymph node structure and lymphatics (with Prof Rod Dunbar),
  4. Medical Devices: Development of technologies for monitoring patient redox status (with Prof John Windsor (Dept Surgery), A/P Paul Kilmartin (chemistry) and Dr Anthony Hickey (SBS).
  5. The role of copper in chronic diseases such as diabetes (with Professor Garth Cooper, SBS) (see {15-16} below
     

 

Projects Available

Philosophy: My laboratory is interested in fostering wide collaborative diversity in our surgical research programs.

 

  • If you are interested Masters or PhD study in any of these general topic areas above (critical illness; mitochondrial failure; lymphatic fluid, insect applications to health, gut-body communication, medical device development, fatty livers, bacteria-host communication), the feel free to contact me to discuss what is available. We always have a wide range of projects available to offer in all these areas, but are also always keen to hear from anyone who thinks they have other interesting surgical or comparative physiology project ideas they would like to suggest to us (Dr Hickey or myself). 
  • If you are a medical trained doctor and come to do a PhD with us, then you will be assigned the joint co-supervision of an academic active clinician and a specialist laboratory scientist. This will ensure you are given input from both clinical and non-clinical perspectives in your project.  I am open to supporting research from any surgical discipline who wants to work with us. Overseas medical doctors are welcome.

If you are not a medical doctor you are also very welcome to contact us: It is not a pre-requisite to be a medical doctor in our lab despite our special focus in that area, so feel free to contact me whatever your background if you are interested in a surgical or comparative physiology related research projects. You can still be exposed to clinical applied projects if this interests you.

 

A selection of some recent publications in these different fields

 

Critical Illness

  1. Mittal, A; Middleditch, M; Ruggiero, K; Buchanan, C.M; Jullig, M; Loveday, B; Cooper, G.J; Windsor, J.A; Phillips, A.R. 'The proteome of rodent mesenteric lymph.', Am J Physiol Gastrointest Liver Physiol, 295, (5), pg895-G903, (2008),
  2. Mittal, A; Phillips, A.R.J; Middleditch, M; Ruggiero, et al. 'The proteome of mesenteric lymph during acute pancreatitis and implications for treatment', Journal of the Pancreas, 10, (2), p130-142, (2009).
  3. Mittal, A; Middleditch, M; Ruggiero, K; Loveday, B; Delahunt, B; Jüllig, M; Cooper, G.J; Windsor, J.A; Phillips, A.R. 'Changes in the mesenteric lymph proteome induced by hemorrhagic shock.', Shock, 34, (2), p140-149, (2010),
  4. Haydock, M. D., Mittal, A., Wilms, H. R., Phillips, A.R, Petrov, M. S., & Windsor, J. A.  Fluid Therapy in Acute Pancreatitis Anybody's Guess. Annals of Surgery, 257(2), 182-188. (2013)

 

Mitochondrial Dysfunction

  1. Mittal, A; Hickey, A.J; Chai, C.C; Loveday, B.P; Thompson, N; Dare, A; Delahunt, B; Cooper, G.J; Windsor, J.A; Phillips, A.R. 'Early organ-specific mitochondrial dysfunction of jejunum and lung found in rats with experimental acute pancreatitis.', HPB (Oxford), 13, p332-341, (2011),
  2. Hickey, A.J; Jüllig, M; Aitken, J; Loomes, K; Hauber, M; Phillips, A.R. 'Birds and longevity: Does flight driven aerobicity provide an oxidative sink?', Ageing Research Reviews 11(2):p242-253, (2012)
  3. Dare, A.J; Phillips, A.R; Hickey, A.J; Mittal, A; Loveday, B; Thompson, N; Windsor, J.A. 'A systematic review of experimental treatments for mitochondrial dysfunction in sepsis and multiple organ dysfunction syndrome.', Free Radic Biol Med, 47, (11), p1517-1525, (2009)

 

ncRNA

  1. Blenkiron, C; Askelund, K.J.; Shanbhag S.T; Chakraborty M; Petrov M.S.; Delahunt, B; Windsor J.A; Phillips, A,R. ‘MicroRNAs In Mesenteric Lymph And Plasma During Acute Pancreatitis’. Annals of Surgery, (2013) In Press’

 

Wound Healing

  1. Gilmartin, D.J; Alexaline M.M; Thrasivoulou C; Phillips A. R; Suwan N. Jayasinghe, S.N; Becker, D.L. ‘Integration of scaffolds into full-thickness skin wounds: the connexin response.’, Adv Healthcare Mater, (2013). DOI: 10.1002/adhm.201200357
  2. Davis N.G; Phillips, A.R; Becker, D.L. ‘Connexin dynamics in the privileged wound healing of the buccal mucosa.’, Wound Rep Reg,. Jul;21(4):571-8. doi: 10.1111/wrr.12054. (2013).
  3. Becker, D.L; Thrasivoulou, C; Phillips, A.R. 'Connexins in wound healing; perspectives in diabetic patients', Biochim et Biophys Acta-Biomem, 1818 (8), p2068–2075, (2012)

 

Hepatic Steatosis

  1. Chu MJJ, Phillips ARJ, Hosking AWG, MacDonald JR, Bartlett ASJR, Hickey, A. Hepatic Mitochondrial Function Analysis Using Needle Liver Biopsy Samples. PLoS ONE 8(10): e79097. doi:10.1371/journal.pone.0079097 (2013)
  2. Dare, A. J., Phillips, A. R. J., Chu, M., Bartlet, A. S. J. R., Hickey, A. J. R., Bartlet, A. S. J. R. Appraisal of donor steatosis in liver transplantation: A survey of current practice in Australia and New Zealand. Transplant Research and Risk Management, 4, 31-37,(2012)
  3. Chu M.J.J; Dare, A; Bartlett, A; Phillips, A.R; Hickey, A. ‘Effect of hepatic steatosis on bioenergetic function during ischaemia-reperfusion: a systematic review’, Open Transpl J, (2013)

 

Copper and Chronic illness

  1. Cooper, G.J; Young, A.A; Gamble, G.D; Occleshaw, C.J; Dissanayake, A.M; Cowan, B.R; Brunton, D.H; Baker, J.R; Phillips, A.R; Frampton, C.M; Poppitt, S.D; Doughty, R.N. 'A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type 2 diabetic patients: a randomised placebo-controlled study.', Diabetologia, 52, (4), p715-722, (2009)
  2. Zhang, L; Phillips, A.R.J; Ward, M.L; Cooper, G.J.S. 'Reversal Of Diabetes-Evoked Changes In Cardiac Function By Treatment With A Copper (Ii)-Selective Chelator', J Physiol Soc, 59, p315-315, 2009.
  3. Zhang, L, Ward, M, Phillips, A.R, Zhang, S, Kennedy, J Barry, B., Cannell, M., Cooper, G. J., Protection of the heart by treatment with a divalent-copper-selective chelator reveals a novel mechanism underlying cardiomyopathy in diabetic rats Cardiovascular Diabetology. 12(1):123. (2013)  DOI:10.1186/1475-2840-12-123

Areas of expertise

Proteomics and Biomedicine

Selected publications and creative works (Research Outputs)