Furness laboratory: Digestive physiology and nutrition

Research Overview

View Professor Furness's latest publication listing here.

The healthy gut communicates with the brain and lives in harmony with the many bacteria it contains.  Disorders of gut health lead to diabetes and metabolic disease, inadequate nutrition, pain, chronic nausea, poor digestion and liver disease.  Major digestive diseases include inflammatory bowel disease, gastroparesis, chronic constipation and the irritable bowel syndrome.

The gut is controlled through an extensive nervous system, the enteric nervous system (ENS), embedded in the gut wall, connections with the central nervous system (CNS) and through gut hormones.  We are intensely interested in these control systems and how they are involved in disordered states, including inflammatory bowel disease, diabetes, obesity, constipation and gastroparesis.

We are working to develop new approaches to treating bowel diseases through electroceuticals, an exciting new approach in which nerves are stimulated to treat disordered function, through drug development and by unravelling the basic mechanisms essential for digestive health.  We are also working to understand the reasons why gastrointestinal functions become disordered when there are pathologies of the central nervous system, such as in Parkinson’s disease.

In drug development, Professor Furness, Dr Ruslan Pustovit and Dr Akhter Hossain are investigating novel targets for treatment of constipation.

Dr Rachel McQuade is investigating the mechanisms that lead to the digestive system manifestations of Parkinson’s Disease and the ways in which they may be treated and consequences of obesity for the enteric nervous system.

Dr Martin Stebbing, Dr Ruslan Pustovit and Dr Juan Molero are investigating gastric innervation and how stimulation of nerves innervating the stomach could be used to treat gastroparesis.

Dr Lalita Oparija is investigating how disruption of feeding and of the sleep-wake cycle, the circadian rhythm, affect gut function and health.

Dr Linda Fothergill is developing a new technology, aptamers, to measure hormone levels, in vivo, and in real time.

In basic mechanisms, we are studying roles of gut hormones and enteric nerves, the mechanisms by which inflammation in the gut is controlled by nerves, the sensory innervation of the stomach and ways of protecting the lining of the gut.

Staff

Dr Martin Stebbing, Senior Research Fellow
Dr Rachel McQuade, Post-doctoral Fellow, NHMRC Emerging Leader
Dr Ruslan Pustovit, Post-doctoral Fellow
Dr Juan Molero, Post-doctoral Fellow
Dr Linda Fothergill, Post-doctoral Fellow
Dr Lalita Oparija, Post-doctoral fellow, Swiss National Science Foundation
Ms Billie Hunne, Research Assistant
Ms Madeleine Di Natalie, Research Assistant
Ms Enie Lei, Research Assistant
Ms Jamie Liew, Research Assistant
Ms Josiane Fakhry, PhD student
Ms Ada Koo, PhD Student
Ms Theresa Fazio-Coles, PhD student
Ms Xin-Yi Chai, PhD student
Mr Mitchell Ringuet, PhD student
Prof Peter McIntyre, Honorary Professor

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
Dr Sebastian Furness, Monash University
Professor Ross Bathgate, Florey Institute
Dr Akhter Hossain, Florey Institute
Professor Clive May, Florey Institute
Dr David Bravo, Geneva, Switzerland
Dr Vicki Lawson, Pathology, University of Melbourne
Dr Sophie Payne, Bionics Institute
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 Lincon Stamp, Anatomy and Neuroscience, University of Melbourne
Dr Marlene Hao, Anatomy and Neuroscience, University of Melbourne
Dr Leni Rivera, Deakin University
Dr Holly Chinnery, Florey Institute
Dr Scott Mueller, Doherty Institute

Funding

Defense Advanced Research Projects Agency (DARPA USA). Cooperative agreement N66001-15-2-4060, JB Furness, RK Shepherd, RM McAllen, DB Grayden, RM Jones, P DeCruz. Vagal neuromodulation for the treatment of inflammatory bowel disease 2015-2021 USD $6,745,866.  Australian dollar value at Feb 2019 = $9,501,220

Takeda Pharmaceutical Co Ltd.  JB Furness. Therapeutic drug development for neuropathies that compromise digestive function.  2015-2020: $3,462,637

NIH SPARC JB Furness.  OT2OD023847 Mapping stomach autonomic circuitry and function for neuromodulation of gastric disorders 2016-2022: Total $1,256,989.74

NHMRC Project Grant APP1145686.  JB Furness, D Finkelstein, V Lawson, Unravelling the neuropathological basis of the gastrointestinal manifestations of Parkinson’s Disease, 2018-2021; $186,476 each year, out-turned, Total: $745,904

NHMRC Ideas Grant APP1182996.  MA Hossain, J Wade, M Kocan, RV Pustovit, JB Furness (AI). Developing relaxin family peptide receptor 4 (RXFP4) agonists as novel tools and therapeutic leads for chronic constipation: 2020 $247,698.70; 2021, $247,698.70; 2022, $163,867.70; 2023 $181,590.20. Total: $840,855.30

NHMRC Ideas Grant. RM McQuade, S Diwakarla, AI JB Furness.  Enteric neuroprotection: A novel therapeutic avenue for Parkinson’s disease, 2020-2023, $961,560

NHMRC Emerging Leadership 1.  RM McQuade.  Protecting the gut: a novel therapeutic avenue for reducing the damaging consequences of obesity.  $570,205

Research Publications

2020

  1. Davey, CE, Shafton, A, McAllen, RM, Furness, JB, Grayden, DB, Stebbing, MJ, A new algorithm for tracking action potentials in recordings from autonomic nerves over time. J Neurosci Methods 338, 108683 (2020). DOI: 10.1016/j.jneumeth.2020.108683
  2. Diwakarla S, Bathgate, RAB, Zhang, X, Hossain, MA and Furness, JB:  Colokinetic effect of an insulin-like peptide 5 related agonist of the RXFP4 receptor.  Neurogastro Motil 32, e13796 (2020)
  3. Diwakarla, S, Finkelstein, DI, Constable, R, Artaiz, O, Di Natale, M, McQuade, RM, Lei, E, Chai, X-y, Ringuet, MT, Fothergill, LJ, Lawson, VA, Ellett, LJ, Berger, JP, Furness, JB:  Chronic isolation stress modifies non-motor symptoms in the A53T mouse model of Parkinson's Disease.  Neurogast Motil 32, e13755 (2020). DOI: 10.1111/nmo.13755
  4. Fazio Coles TE, Fothergill LJ, Hunne, B, Nikfarjam, M, Testro, A, Callaghan, B, McQuade, RM, Furness, JB: Quantitation and chemical coding of enteroendocrine cell populations in the human jejunum. Cell & Tissue Res 379, 109-120 (2020).  DOI: 10.1007/s00441-019-03099-3
  5. Payne, SC, Alexandrovics, J, Thomas, R, Shepherd, RK, Furness, JB, Fallon, JB: Transmural impedance detects graded changes of inflammation in experimental colitis.  Roy Soc Open Sci 7: 191819.  DOI: 10.1098/rsos.191819
  6. Shakeri M, Cottrell JJ, Wilkinson S, Zhao W, Le HH, McQuade R, Furness JB, Dunshea FR. Dietary betaine improves intestinal barrier function and ameliorates the impact of heat stress in multiple vital organs as measured by evans blue dye in broiler chickens. Animals. 10, 38, 1-14 (2020).  DOI:10.3390/ani10010038
  7. Ward MP, Gupta, A, Wo, JM, Rajwa, B, Furness, JB, Powley, TL, Nowak, TV.:  An emerging method to noninvasively measure and identify vagal response markers to enable bioelectronic control of gastroparesis symptoms with gastric electrical stimulation.  J Neurosci Methods 326, 108631 (2020). doi.org/10.1016/j.jneumeth.2020.108631

2019

  1. Craig JR, Dunshea FR, Cottrell JJ, Furness JB, Wijesiriwardana UA, Pluske JR: A comparison of the anatomical and gastrointestinal functional development between gilt and sow progeny around birth and weaning. J Anim Sci 97, 3809-3822 (2019).  DOI: 10.1093/jas/skz217
  2. Fakhry, J, Stebbing, MJ,Hunne, B, Bayguinov, Y, Ward, SM, Sasse, KC, Callaghan, B, McQuade, RM, Furness, JB:  Relationships of endocrine cells to each other and to other cell types in the human gastric fundus and corpus.  Cell & Tissue Res 376, 37-49 (2019), DOI: 10.1007/s00441-018-2957-0
  3. Fothergill, LJ, Galiazzo, G, Hunne, B, Stebbing, MJ, Fakhry, J, Weissenborn, F, Fazio Coles, T, Furness, JB: Distribution and coexpression patterns of specific cell markers of enteroendocrine cells in pig gastric epithelium.  Cell & Tissue Research 378, 457–469 (2019)
  4. Fothergill, LJ, Ringuet, MT, Sioras, E, Hunne, B, Coles, TF, Martins, P, Furness, JB: Localisation of oxyntomodulin and implications for processing of proglucagon derived peptides in human, mouse, pig, and rat.  Cell & Tissue Res 375, 359-369 (2019).  doi.org/10.1007/s00441-018-2921-z
  5. Furness, JB, Fakhry, J, Gajewski, J, Boyle, EK, Fothergill, LJ: The digestive system in evolutionary medicine. In Oxford Handbook of Evolutionary Medicine, Ed: Martin Brüne and Wulf Schiefenhövel.  Oxford University Press, pp531-562 (2019).
  6. Hunne, B, Stebbing, MJ, McQuade, RM, Furness, JB: Distributions and relationships of chemically defined enteroendocrine cells in the rat gastric mucosa.  Cell & Tissue Research 378, 33-48 (2019) DOI: 10.1007/s00441-019-03029-3
  7. Payne, SC, Furness, JB, Burns, O, Sedo, A, Hyakumura, T, Shepherd, RK, Fallon, JB,: Anti-inflammatory effects of abdominal vagus nerve stimulation on experimental intestinal inflammation.  Frontiers Neuroscience 13, 418, 1-15 (2019).  DOI  10.3389/fnins.2019.00418
  8. Payne SC, Furness JB, Stebbing, MJ:  Bioelectric neuromodulation for gastrointestinal disorders: effectiveness and mechanisms. Nature Rev Gastro Hepatol 16, 89–105 (2019) DOI: 10.1038/ s41575-018-0078-6
  9. Pustovit, RV, Itomi, Y, Ringuet, M, Diwakarla, S, Chai, X-y, McQuade, RM, Tsukimi, Y, Furness, JB:  Muscarinic receptor 1 allosteric modulators stimulate colorectal emptying in dog, mouse and rat and resolve constipation.  Neurogastro Motil 13 e13692 (2019) DOI: 10.1111/nmo.13692

2018

  1. Callaghan, B, Furness, JB, Pustovit, RV:  Neural pathways for colorectal control, relevance to spinal cord injury and treatment. Spinal Cord 56, 199-205 (2018), doi:10.1038/s41393-017-0026-2
  2. Fothergill, LJ, Furness, JB:  Diversity of enteroendocrine cells investigated at cellular and subcellular levels: the need for a new classification scheme.  Histochem Cell Biol 150, 693-702 (2018) https://doi.org/10.1007/s00418-018-1746-x
  3. Furness, JB, Stebbing MJ: The first brain: species comparisons and evolutionary implications for the enteric and central nervous systems.  Neurogast Motil ;30, e13234, 1-6.  DOI: 10.1111/nmo.13234 (2018)
  4. Johnson, CD, Barlow-Anacker, AJ, Pierre, JF, Touw, K, Erickson, CS, Furness, JB, Epstein, ML, Gosain, A:  Deletion of choline acetyltransferase in enteric neurons results in postnatal intestinal dysmotility and dysbiosis. FASEB Journal 32, 4744-4752 (2018) DOI: 10.1096/fj.201701492R
  5. McAllen, RM, Shafton, AD, Bratton, BO, Trevaks D, Furness JB:  Calibration of thresholds for functional engagement of vagal A, B and C fiber groups in vivo. Bioelectron Med, DOI: 10.2217/bem-2017-0001 (2018) epub online
  6. O’Sullivan-Greene E, Kameneva, T, Trevaks D, Shafton, A, Payne SC, McAllen, R, Furness, JB, Grayden, DB: Modeling experimental recordings of vagal afferent signaling of intestinal inflammation for neuromodulation.  J Neural Eng 15, 056032 (2018). DOI: 10.1088/1741-2552/aad96d
  7. Payne, SC, Shepherd, RK, Sedo, A, Fallon, JB, Furness JB:  An objective in vivo diagnostic method for inflammatory bowel disease.  Royal Society Open Science 5: 180107 (2018) DOI: 10.1098/rsos.180107
  8. Shakeri M, Cottrell JJ, Wilkinson, S, Ringuet, MT, Furness, JB, Dunshea FR: Betaine and anti-oxidants improve growth performance, breast muscle development and ameliorate thermoregulatory responses to cyclic heat exposure in broiler chickens. Animals 8, 162 (2018); doi:10.3390/ani8100162
  9. Payne, SC, Burns, O, Stebbing, M, Thomas, R, De Silva, A, Sedo, A, … Furness, JB, Fallon, J,, Shepherd RK. Vagus nerve stimulation to treat inflammatory bowel disease: a chronic, preclinical safety study in sheep. Bioelectron. Med. 1 (4). (2018). https://doi.org/10.2217/bem-2018-0011

2017

  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. 170, 49-53 doi: 10.1016/j.jsbmb.2016.07.005 (2017).
  2. Au, CC, Furness, JB, Brown, KA:  Ghrelin and breast cancer: emerging roles in obesity, estrogen regulation, and cancer. Frontiers in Oncology. 6 (265) 1-7.  doi: 10. 3389/fonc.2016.00265 (2017).
  3. Diwakarla, S, Fothergill, LJ, Fakhry, J, Callaghan, B, Furness, JB: Heterogeneity of enterochromaffin cells within the gastrointestinal tract.  Neurogastroenterol Motil. 29: e13101. doi: 10.1111/nmo.13101 (2017)
  4. 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. 69, 245-253.  doi:10.1007/s00441-017-2612-1 (2017)
  5. 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 158, 2113-2123 (2017) doi: 10.1071/AN17276
  6. Furness, JB: The physiological relevance of constriction of mesenteric arteries by topically applied noradrenaline.  J. Physiol. 595, 6783-6784
  7. Furness, JB, Cottrell, JJ: Signalling from the gut lumen. Animal Production Science 57, 2175-2187 (2017) doi: 10. 3389/fonc.2016.00265
  8. 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. 367, 361-368 (2017) doi:10.1007/s00441-016-2530-7.
  9. Pustovit, RV,Callaghan, B, Ringuet, MT, Kerr, NF, Hunne, B, Smyth, IM, Pietra, C, Furness, JB:  Evidence that central pathways that mediate defecation utilise ghrelin receptors but do not require endogenous ghrelin.  Physiol Reports, 5, e13385 (2017) https://doi.org/10.14814/phy2.13385
  10. Sanger, GJ, Broad, J, Callaghan, B, Furness, JB:  Ghrelin and motilin control systems in GI physiology and therapeutics.  Handbook of Pharmacology Gastrointestinal Pharmacology, 379-416 (2017). doi 10.1007/164_2016_104

Research Projects


Faculty Research Themes

Infection and Immunology, Neuroscience

School Research Themes

Biomedical Neuroscience, Molecular Mechanisms of Disease, Therapeutics & Translation


Key Contact

For further information about this research, please contact Head of Laboratory Professor John Furness

Department / Centre

Anatomy and Physiology

Unit / Centre

Furness laboratory: Digestive physiology and nutrition

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