Furness laboratory: Digestive physiology and nutrition

Research Overview

Our research is concentrated on digestive physiology, gut health, the interaction of nutrients with the digestive tract and digestive disorders.  The investigations extend from molecular studies of sites of drug action and the cellular basis of pathological changes, through the investigation of functions in isolated tissues and the use of animal models to clinical trials. Our work spans both human and animal health, in animal health concentrating on species of agricultural importance.

The laboratory is led by Professor John B Furness, who is a full time research scientist with appointments in Anatomy and Neuroscience, Veterinary and Agricultural Science and the Florey Institute of Neuroscience and Mental Health.

In relation to gut health, we have studies directed at investigating drugs that can be used in the treatment of disorders of digestive tract function that are a consequence of spinal cord injury, neuropathologic changes in gut neurons that are a results of high fat diets and Parkinson's Disease, deleterious effects of heat stress on the intestine, and consequences of inflammation of the intestine.  We are investigating drug treatments for motility disorders and enteric neuropathies and electroceutical treatments (stimulation of the vagus nerve) for inflammatory bowel diseases. We are also investigating aspects of celiac disease.

We have a particular interest in endocrine hormone secreting cells of the gastrointestinal tract.  We have made discoveries that demand re-classification of these cells and a re-thinking of their cell biology.  This work is relevant to celiac disease, diabetes, obesity and metabolic disease.

Staff

Dr Brid Callaghan, Post-doctoral Fellow
Dr Shanti Diwakarla, Post-doctoral Fellow 
Dr Ruslan Pustovit, Post-doctoral Fellow
Dr Tony Shafton, Post-doctoral Fellow
Ms Billie Hunne, Research Assistant
Mr Mitchell Ringuet, Research Assistant
Mr Remy Constable, Research Assistant
Ms Alicia Sedo, Research Assistant
Ms Josiane Fakhry, PhD student
Ms Linda Fothergill, PhD student
Ms Theresa Fazio-Coles, MSc student
Ms Xin-Yi Chai, Honours student
Dr Joanna Gajewski, Program manager

Collaborators

Professor Robin McAllen, Florey Institute
Professor Rob Shepherd, Bionics Institute
Professor Terry Powley, Purdue University, Indiana, USA
Professor Bob Jones, Surgery, Austin Health
Dr Peter de Cruz, Austin Health
Dr David Finkelstein, Florey Institute
Professor Michael McKinley, Florey Institute
Professor Clive May, Florey Institute
Dr David Bravo, Geneva, Switzerland
Dr Vicki Lawson, Pathology, University of Melbourne
Dr Donald Newgreen, Murdoch Institute
Dr Sophie Payne, Bionics Institute
Dr Christopher Leung, Gastroenterology, Austin Health
Dr Kristy Brown, Columbia University, New York
Professor Frank Dunshea, Veterinary and Agricultural Sciences, University of Melbourne
Dr Jeremy Cottrell, Veterinary and Agricultural Sciences, University of Melbourne
Dr Adam Testro, Liver Transplant Unit, Austin Health
Dr Lincon Stamp, Anatomy and Neuroscience, University of Melbourne
Dr Marlene Hao, Anatomy and Neuroscience, University of Melbourne
Professor Albert Frauman, Dept Clinical Pharmacology, University of Melbourne
Dr Heather Young, Anatomy and Neuroscience, University of Melbourne
Professor Graeme Clarke, NICTA
Dr Leni Rivera, Deakin University

Funding

TAC Project Grant N13-085
JB Furness, B Callaghan, AG Frauman, LR Rivera, A Nunn, DJ Brown, A Ellis: "Reduction of Secondary Complications of Spinal Cord Injury: Bowel", 2014-2017, $1,060,000
ARC LIEF grant, LE150100004
E Hanssen, A Bacic, G McFadden, M McConville, JB Furness, D McCulloch, V Bansal, K North.  "An automated 3D electron microscopy facility", 2014-, $540,000
NHMRC Project Grant 1079739
JB Furness and LR Rivera - "Neural control of colorectal function and identification of sites of drug action": 2015 $92,359.00, 2016 $92,359.00, 2017 $177,825.00.
Australian Pork Ltd
J Pluske, FR Dunshea, JB Furness, JJ Cottrell, C Collins, R Hewitt, JC Kim, B Mullan, S Peuker, R van Barneveld, "Optimising the progeny of first-litter sows in the Australian herd", 2015-2018, $944,081
Defense Advanced Research Projects Agency (DARPA USA) 
JB Furness et al. "Vagal neuromodulation for the treatment of inflammatory bowel disease", 2015-2019, $6,100,000
NIH SPARC
JB Furness.  "Mapping stomach autonomic circuitry and function by neuromodulation of gastric disorders", 2017-2019, $697,825
NHMRC Project Grant 1125805 
DF Newgreen, GG Qiao, JM Hutson, SK King, JB Furness - "Novel cell therapy for Hirschsprung Disease: from patient iPS cells to large animal trials": 2017-2019, $1,011,764

Research Publications

2017

  1. Au CC, Furness JB, Brown KA.  Ghrelin and breast cancer: emerging roles in obesity, estrogen regulation, and cancer. Frontiers in Oncology 2017; 6(265): 1-7.  doi: 10. 3389/fonc.2016.00265.
  2. Diwakarla S, Fothergill LJ, Fakhry J, Callaghan B, Furness JB. Heterogeneity of enterochromaffin cells within the gastrointestinal tract.  Neurogastroenterol Motil. Accepted April  (2017)
  3. Fakhry J, Wang J, Martins P, Fothergill LJ, Hunne B, Prieur P, Shulkes A, Rehfeld JF, Callaghan B, Furness JB. Distribution and characterisation of CCK containing enteroendocrine cells of the mouse small and large intestine.  Cell Tissue Res 2017; Published on line doi:10.1007/s00441-017-2612-1
  4. Fothergill LJ, Callaghan B, Hunne B, Bravo DM, Furness JB.  Co-storage of enteroendocrine hormones evaluated at the cell and subcellular levels in male mice.  Endocrinology accepted 13 April 2017
  5. Martins P, Fakhry J, Chaves de Oliveira E, Hunne B, Fothergill LJ, Ringuet M, d’Ávila Reis D, Rehfeld JF, Callaghan B, Furness JB. Analysis of enteroendocrine cell populations in the human colon.  Cell Tissue Res 2017; 367: 361-368. doi:10.1007/s00441-016-2530-7.
  6. Sanger GJ, Broad J, Callaghan B, Furness JB.  Ghrelin and motilin control systems in GI physiology and therapeutics.  Handbook of Pharmacology doi 2016; 10.1007/164_2016_104.

2016

  1. Au CC, Docanto MM, Zahid H, Raffaelli FM, Ferrero RL, Furness JB, Brown KA. Des-acyl ghrelin inhibits the capacity of macrophages to stimulate the expression of aromatase in breast adipose stromal cells. J Steroid Biochem Mol Biol 2016 Jul 14; doi: 10.1016/j.jsbmb.2016.07.005
  2. Edgington-Mitchell LE, Wartmann T, Fleming AK, Gocheva V, van der Linden WA, Withana NP, Verdoes M, Aurelio L, Edgington-Mitchell D, Lieu TM, Parker BS, Graham B, Reinheckel T, Furness JB, Joyce JA, Storz P, Halangk W, Bogyo M, Bunnett NW. Legumain is activated in macrophages during pancreatitis. Am J Physiol 2016; 311: G548-G560.
  3. Ellett LJ, Hung LW, Munckton R, Sherratt NA, Culvenor J, Grubman A, Furness JB, White AR, Finkelstein DI, Barnham KJ, Lawson VA. Restoration of gastrointestinal function in an MPTP model of Parkinson’s Disease. Scientific Reports 2016; 6: 30269. DOI: 10.1038/srep30269.
  4. Fothergill LJ, Callaghan B, Rivera LR, Lieu TM, Poole DP, Cho H-J, Bravo DM, Furness JB. Effects of food components that activate TRPA1 receptors on mucosal ion transport in the mouse intestine. Nutrients 2016 Oct 10; 8(10): pii: E623.  doi:10.3390/nu8100623
  5. Furness JB.  Integrated neural and endocrine control of gastrointestinal function.  Advances Exp Med Biol 2016; 891: 159-173.
  6. Furness JB, Poole DP, Cho H-J, Callaghan B, Rivera LR.  The innervation of the gastrointestinal tract. In: D. Podolsky (Ed), Yamada’s Textbook of Gastroenterology, 6th Edition, Wiley: Chichester. Pp 239-258 (2016)
  7. Leung C, Herath CB, Jia Z, Andrikopoulos S, Brown BE, Davies MJ, Rivera LR, Furness JB; Forbes JM, Angus PW.  Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease.  World J Gastroenterol 2016; 22: 8026-8040.
  8. Leung C, Rivera LR, Angus PW, Furness JB. The role of the gut microbiota in NAFLD. Nature Rev Gastroenterol Hepatol 2016; 13: 412-425.
  9. Liu F, Cottrell JJ, Furness JB, Rivera LR, Kelly FW, Wijesiriwardana U, Pustovit RV, Fothergill LJ, Bravo DM, Celi P, Leury LJ, Gabler NK, Dunshea FR.  Selenium and vitamin E together improve intestinal epithelial barrier function and alleviate oxidative stress in heat stressed pigs. Exp Physiol 2016; 101: 801-810.
  10. Parish IA, Stamp LA, Lorenzo A, Fowler S, Sontani Y, Miosge LA, Howard DR, Goodnow CC, Young HM, Furness JB. A novel mutation in the nucleoporin NUP35 causes murine degenerative colonic smooth muscle myopathy.  Am J Pathol 2016; 186: 2254-2261.
  11. Reynaud Y, Fakhry J, Fothergill LJ, Callaghan B, Ringuet M, Hunne B, Bravo DM, Furness JB.  The chemical coding of 5-hydroxytryptamine containing enteroendocrine cells in the mouse gastrointestinal tract. Cell Tissue Res 2016; 364: 489-497.
  12. Sanger GJ, Furness JB. Ghrelin and motilin receptors as drug targets for gastrointestinal disorders. Nature Rev Gastroenterol Hepatol 2016; 19: 38-48.
  13. Spiers K, Cardamone T, Furness JB, Clark JM, Patrick J, Clark GM.  An X-ray fluorescence microscopic analysis of the tissue surrounding the multi-channel cochlear implant electrode array.  Cochlear Implants Internat 2016; 17: 129-131.

2015

  1. Broad J, Callaghan B, Sanger GJ, Brock JA, Furness JB.  Analysis of the ghrelin receptor-independent vascular actions of ulimorelin.  Europ J Pharmacol 2015; 752: 34-39.
  2. Cho HJ, Kosari S, Hunne B, Callaghan B, Rivera LR, Bravo DM, Furness JB.  Differences in hormone expression patterns of K-L enteroendocrine cells in the mouse and pig small intestine and colon.  Cell Tissue Res 2015; 359: 693-698.
  3. Cottrell JJ, Liu F, Hung AT, DiGiacomo K, Chauhan SS, Leury BJ, Furness JB, Celi P, Dunshea FR. Nutritional strategies to alleviate heat stress in pigs.  Animal Production Science 2015; 55: 1391-1402.
  4. Ellis AG, Zeglinski PT, Brown DJ, Frauman AG, Millard M, Furness JB. Pharmacokinetics of the ghrelin agonist capromorelin in a single ascending dose phase 1 safety trial in spinal cord injured and able bodied volunteers. Spinal Cord 2015; 53: 103-108.
  5. Furness J.  Enteric Nervous System: Structure, Relationships and Functions.  In: Reference Module in Biomedical Sciences, Ed M Caplan, Elsevier, New York (2014) doi:10.1016/B978-0-12-801238-3.04584-0. (2014)
  6. Furness JB, Bravo DM. Humans as cucinivores: comparisons with other species. J Comp Physiol B 2015; 185: 825-834.
  7. Furness JB, Cottrell JJ, Bravo DM. Comparative physiology of digestion. J Anim Sci 2015; 93: 485-491.
  8. Naitou K, Mamerto TP, Pustovit RV, Callaghan B, Rivera LR, Chan AJ, Ringuet MT, Pietra C, Furness JB.  Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01.  Neurogastroenterol Motil 2015; 27: 1596-1603.
  9. Pustovit RV, Furness JB, Rivera LR.  A ghrelin receptor agonist is an effective colokinetic in rats with diet induced constipation. Neurogastroenterol Motil 2015; 27: 610-617.
  10. Stamp LA, Obermayr F, Pontell L, Young HM, Xie D, Croaker D, Song Z-M, Furness JB. Surgical intervention to rescue Hirschsprung disease in a rat model.  J Neurogastroenterol Motil 2015; 27: 552-559.

2014

  1. Callaghan B, Furness JB.  Novel and conventional receptors for ghrelin, desacyl-ghrelin and pharmacologically related compounds.  Pharmacol Rev 2014; 66: 984-1001.
  2. Callaghan B, Kosari S, Pustovit RV, Sartor DM, Ferens DP, Ban K, Baell J, Nguyen TV, Rivera LR, Brock JA, Furness JB. Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor. Brit J Pharmacol 2014; 171: 1275-1286.
  3. Cho H-J, Callaghan B, Bron R, Bravo DM, Furness JB.  Identification of enteroendocrine cells that express TRPA1 channels in the mouse intestine.  Cell and Tissue Res 2014; 356: 77-82.
  4. Cho H-J, Robinson ES, Rivera LR, McMillan PJ, Testro A, Nikfarjam M, Bravo DM, Furness JB.  Glucagon like peptide 1 and peptide YY are in separate storage organelles in enteroendocrine cells.  Cell and Tissue Res 2014; 357: 63-69.
  5. Clark GM, Clark J, Cardamone T, Clarke M, Nielsen P, Jones P, Arhatari B, Birbilis N, Curtain R, Xu J, Wagstaff S, Gibson P, O’Leary S, Furness JB.  Biomedical studies on temporal bones of the first multi-channel cochlear implant patient at the University of Melbourne.  Cochlear Implants International 2014; 15, Supplement 2: S1-S15.  doi.org/10.1179/1754762814Y.0000000087
  6. Docanto MM, Yang F, Callaghan B, Ragavan R, Wang X, Furness JB, Andrews ZB, Brown KA.  Ghrelin and des-acyl ghrelin inhibit aromatase expression and activity in human adipose stromal cells: suppression of cAMP as a possible mechanism.  Breast Cancer Research and Treatment 2014; 147: 193-201.
  7. Furness JB.  Peripheral autonomic nervous system. In Paxinos, G (Ed). The rat nervous system, 4th edition.  Elsevier, Amsterdam pp 61-76 (2014).
  8. Furness JB, Callaghan B, Rivera LR, Cho H-J.  The enteric nervous system and gastrointestinal innervation: Integrated local and central control.  In: Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease.  Edited by Lyte, M, Cryan, JF.  Advances Exp Med Biol 2014; 817: 39-71.
  9. Gwynne RM, Clarke AJ, Furness JB, Bornstein JC:  Both exogenous 5-HT and endogenous 5-HT, released by fluoxetine, enhance distension evoked propulsion in guinea-pig ileum in vitro.  Frontiers in Neuroscience 2014; 8(301): 1-9.  doi: 10.3389/fnins.2014.00301
  10. Maseko T, Dunshea FR, Howell KS, Cho HJ, Rivera LR, Furness JB,  Ng K.  Selenium-enriched Agaricus bisporus mushroom protects against increase in gut permeability and up-regulates glutathione peroxidase 1 and 2 in hyperthermally induced oxidative stress in rats.  Nutrients 2014; 6: 2478-2492.
  11. Pustovit RV, Callaghan B, Kosari, Rivera LR, Thomas H, Brock JA, Furness JB. The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin.  Neurogastroenterol Motil 2014; 26: 264-271.
  12. Rivera LR, Leung C, Pustovit RV, Hunne B, Andrikopoulos S, Herath C, Testro A, Angus PW, Furness JB. Damage to enteric neurons occurs in mice that develop fatty liver disease but not diabetes in response to a high fat diet.  Neurogastroenterol Motil 2014; 26: 1188-1199.

2013

  1. Bron R, Yin Y, Russo D, Furness JB.  Expression of the ghrelin receptor gene in neurons of the medulla oblongata of the rat. J Comp Neurol 2013; 521: 2680-2702. Doi:10.1002/cne.23309.
  2. Callaghan B, Furness JB. New roles of serotonin and tachykinins in intestinal mucositis? Digestive Diseases and Science 2013; 58: 3384-3385.
  3. Clark GM, Clark JCM, Furness JB.  The evolving science of cochlear implants.  J Am Med Assoc 2013; 310: 1225-1226.
  4. Furness JB, Rivera LR, Cho H-J, Bravo DM, Callaghan B. The gut as a sensory organ. Nature Rev Gastroenterol Hepatol 2013; 10: 729-740.
  5. Hotta R, Stamp LA, Foong JPP, McConnell SN, Bergner AJ, Anderson RB, Enomoto H, Newgreen DF, Obermayr F, Furness JB, Young HM. Transplanted progenitors generate functional enteric neurons in the postnatal colon.  J Clin Invest 2013; 123: 1182-1191.
  6. Reantragoon R, Corbett AJ, Gherardin NA, Sakala IG, Furness JB, Chen Z, Eckle SBG, Birkinshaw R, Patel O, Kostenko L, Meehan B, Kedzierska K, Liu L, Fairlie DP, Hansen TH, Godfrey DI, Rossjohn J, McCluskey J, Kjer-Nielsen L.  Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells.  J Exp Med 2013; 210: 2305-2320.

2012

  1. Al Dera H, Habgood M, Furness JB, Brock JA.  Prominent contribution of L-type Ca2+ channels to cutaneous neurovascular transmission that is revealed after spinal cord injury augments vasoconstriction.  Am J Physiol 2012; 302: H752-H762.
  2. Callaghan B, Hunne B, Hirayama H, Sartor DM, Nguyen TV, Abogadie FC, Ferens D, McIntyre P, Ban K, Baell J, Furness JB, Brock JA. Sites of action of ghrelin receptor ligands in cardiovascular control. Am J Physiol Heart and Circ 2012; 303: H1011-H1021.
  3. Foong JPP, Nguyen TV, Furness JB, Bornstein JC, Young HM.  Myenteric neurons of the mouse small intestine undergo significant electrophysiological and morphological changes during postnatal development. J Physiol 2012; 590: 2375-2390.
  4. Furness JB.  The enteric nervous system and neurogastroenterology. Nature Rev Gastroenterol Hepatol 2012; 9: 286-294.
  5. Furness JB, Cho H-J, Hunne B, Hirayama H, Callaghan BP, Lomax AE, Brock JA.  Identification of neurons that express ghrelin receptors in autonomic pathways originating from the spinal cord.  Cell & Tissue Res 2012; 348: 397-405.
  6. Furness JB, Poole DP.  Involvement of gut neural and endocrine systems in pathological disorders of the digestive tract.  J Anim Sci 2012; 90: 1203-1212.
  7. Poole DP, Furness J.B. Enteric nervous system structure and neurochemistry related to function and neuropathology.  In:  Physiology of the Gastrointestinal Tract Fifth edition. Ed L R Johnson.  Chapter 19, pp 557- 581. Elsevier Academic Press (2012).
  8. Rivera LR, Pontell L, Cho H-J, Castelucci P, Thacker M, Poole DP, Frugier T, Furness JB: Knock out of neuronal nitric oxide synthase exacerbates intestinal ischemia/reperfusion injury in mice.  Cell & Tissue Res 2012; 349: 565-576.
  9. Roberts JA, Lukewich MK, Sharkey KA, Furness JB, Mawe GM, Lomax AE. The roles of purinergic signaling during gastrointestinal inflammation.  Current Opinion in Pharmacology 2012; 12: 659-666.
  10. Wookey PJ, Turner K, Furness JB.  Transient expression of the calcitonin receptor by enteric neurons of the embryonic and early post-natal mouse. Cell & Tissue Res 2012; 347: 311-317.