Furness laboratory: Digestive physiology and nutrition

• Head of Laboratory
  Professor John Furness

  j.furness@unimelb.edu.au
  

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, Hirschsprung disease, chronic constipation and 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.

We are working to develop new approaches to treating bowel diseases through stem cell therapy, through drug development, by restricting inflammation and by unravelling the basic mechanisms essential for digestive health.

Dr Madeleine, Dr Di Natale and Professor Furness are working to unravel the complexities of the stomach’s control systems, and to investigate disorders of the stomach, along with collaborators at Michigan University and the University of Auckland.

Professor Furness and Dr Di Natale and are also investigating the neural control of intestinal inflammation and therapies for inflammatory bowel disease, research that involves a team of neuroscientists, physiologists, clinicians and bioengineers working closely together.  This collaboration includes researchers at Melbourne University, the Royal Melbourne Hospital and in the United States.

The laboratory is closely involved in a major research program with Drs Lincon Stamp and Marlene on the use of stem cells to repair neuronal deficits in gastrointestinal disease, Hirschsprung Disease, gastroparesis and achalasia.

Staff

Dr Madeleine Di Natalie, Post-Doc
Professor John Furness
Ms Billie Hunne, Research Assistant

Collaborators

Professor Robin McAllen, Florey Institute
Dr Peter de Cruz, Austin Health
Dr Sebastian Furness, University of Queensland
Professor Ross Bathgate, Florey Institute
Dr Akhter Hossain, Florey Institute
Dr Sophie Payne, Bionics Institute
Professor Zhongming Liu, University of Michigan
Dr Lincon Stamp, Anatomy and Neuroscience, University of Melbourne
Dr Marlene Hao, Anatomy and Neuroscience, University of Melbourne
Dr Britt Christensen, Royal Melbourne Hospital
Dr Tamara Mogilevski, Monash University and Alfred Health
Dr Aysha Al-Ani, Royal Melbourne Hospital
Dr Katie Davey, Biomedical Engineering, University of Melbourne
Professor Scott Mueller, Doherty Institute

Funding

Takeda Pharmaceutical Co Ltd.  JB Furness. Therapeutic drug development for neuropathies that compromise digestive function.  2015-2023: $3,462,637

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

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

Research Opportunities

This research project is available to PhD students, Masters by Research, Honours students, Master of Biomedical Science, Post Doctor Researchers to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Publications

2024

1. Athavale ON, Avci, R, Clark, AR, Di Natale, MR, Wang, X, Furness, JB, Liu, ZM, Cheng, LK, Du, P: Neural regulation of slow waves and phasic contractions in the distal stomach: a mathematical model.  J Neural Engineering, 20, 066040 (2024). doi.org/10.1088/1741-2552/ad161
2. Dehkhoda, F., Ringuet, M.T., Whitfield, E.A., Mutunduwe, K., Nowell, C.J., Misganaw, D., Xu, Z., Hossain, A.M., Fothergill, L.J., McDougall, S.J. and Furness, J.B., 2023. Re-coding of G protein-coupled receptor signaling enables emergent cellular BioRxiv  doi/10.1101/2023.12.18.572241v2
3. Di Natale, MR, Hunne, B, Stebbing, MJ, Wang, X, Liu, ZM, Furness, JB: Characterization of neuromuscular transmission and projections of muscle motor neurons in the rat stomach.  Am J Physiol – GI and Liver 326, G78-G93 (2024) doi.org/10.1152/ajpgi.00194.2023
4. Di Natale, MR, McQuade, R, Hunne, B, Koo, A, Ringuet, M, Coles, T, Fothergill, LJ, Furness, JB, Oparija-Rogenmozere, L:  Food entrainment in mice leads to sex- and organ-specific responses in nutrient metabolism. BioRxiv  doi /10.1101/2024.02.20.580958
5. Stebbing, MJ, Shafton, A, Davey, CE, Di Natale MR, Furness, JB, McAllen, RM: A ganglionic intestino-intestinal reflex activated by acute noxious challenge. Am J Physiol – GI and Liver 326, G360-G373 (2024) doi.org/10.1152/ajpgi.00145.2023
6. Trevizan-Baú, P, Ringuet, MT, Stebbing, MJ, McAllen, RM, Furness, JB, Mueller, SN: Protocol for the isolation of the mouse sympathetic splanchnic-celiac-superior mesenteric ganglion complex.  STAR Protocols 5, 103036 doi.org/10.1016/j.xpro.2024.103036

2023

7. Di Natale, MR, Athavale, ON, Wang, X, Du, P, Cheng, LK, Liu, Z, Furness, JB: Functional and anatomical gastric regions and their relations to motility control.  Neurogast Motil, 35:e14560 (2023) doi.org/10.1111/nmo.14560
8. Di Natale, MR, Hunne, B, Stebbing, MJ, Wang, X, Liu, ZM, Furness, JB: Characterization of neuromuscular transmission and projections of muscle motor neurons in the rat stomach.  Am J Physiol – GI and Liver 326, G78-G93 (2024) doi.org/10.1152/ajpgi.00194.2023 (on line 21 November (2024)
9. Furness, JB, Lei, E, Hunne, B, Adams, CD, Burns, AJ, Wykosky, J, Fazio Coles, TE, Fothergill, LJ, Molero, JC, Pustovit, RV, Stamp, LA: Development of the aganglionic colon following surgical rescue in a cell therapy model of Hirschsprung disease in rat.  Disease Models & Mechanisms 16, dmm050055.  https://doi.org/10.1242/dmm.050055
10. Ringuet, MT, Koo, A, Furness, SGB, McDougall SJ & Furness, JB:  Sites and mechanisms of action of colokinetics at dopamine, ghrelin and serotonin receptors in the rodent lumbosacral defecation centre.  J. Physiol. 601, 5195-5211 (2023) doi.org/10.1113/JP285217.  Featured in Translational Perspective:  Browning, K.N., 2023. Colokinetic co‐operation to control colorectal motility. J. Physiol.. doi.org/10.1113/JP285688
11. Song, Y, Fothergill, LJ, Lee, KS, Liu, BY, Koo, A, Perelis M, Diwakarla, S, Callaghan, B, Huang, J, Wykosky, J, Furness, JB, Yeo, GW:  Stratification of enterochromaffin cells by single-cell expression analysis.  BioRxiv, doi: https://doi.org/10.1101/2023.08.24.554649
12. Wang, X, Cao, J, Han, K, Choi, M, She, Y, Scheven, U, Du, P, Cheng, L, Di Natale, MR, Furness, JB, Liu, Z:  Diffeomorphic surface modeling for MRI-based characterization of gastric anatomy and motility.  IEEE Transactions on Biomedical Engineering (TBME) 70, 2046-2057 (2023) Doi.org/10.1109/TBME.2023.3234509

2022

13. Avci R, Wickens, JD, Sangi, M, Athavale, ON, Di Natale, MR, Furness, JB, Du, P, Cheng, LK.:  A computational model of biophysical properties of the rat stomach informed by comprehensive analysis of muscle anatomy. IEEE Engineering in Medicine and Biology 2022, 4954-4957 (2022). Doi: 10.1109/EMBC48229.2022.9871314
14. Di Natale, MR, Hunne, B, Liew, JJM, Fothergill, LJ, Stebbing, MJ, Furness, JB:Morphologies, dimensions and targets of gastric nitric oxide synthase neurons.  Cell and Tissue Research 388, 19-32 (2022) doi.org/10.1007/s00441-022-03594-0.
15. Di Natale MR, Patten L, Molero JC,Stebbing, MJ, Hunne B, Wang X, Liu Z, Furness, JB: Organisation of the musculature of the rat stomach.  J Anat. 240, 711-723 (2022) doi: 10.1111/joa.13587
16. Furness, JB:  Comparative and evolutionary aspects of the digestive system and its enteric nervous system control.  Adv exp Biol Med 1383, 165-177(2022). https://doi.org/10.1007/978-3-031-05843-1_16
17. Koo, A, Pustovit, RV, Woodward, ORM, Lewis, JE, Gribble, FM, Hossain, MA, Reimann, F, Furness^, JB: Expression of the relaxin family peptide 4 receptor by enterochromaffin cells of the mouse large intestine.  Cell Tissue Res 389,1-9 (2022)  doi.org/10.1007/s00441-022-03635-8
18. Ringuet MT, Furness, JB, Furness, SGB:  G protein-coupled receptor interactions and modification of signalling involving the ghrelin receptor, GHSR1a.  J. Neuroendocrinology 34, e13077 (2022).  https://doi.org/10.1111/jne.13077
19. Stamp, LA, Lei, E, Liew, JJ, Pustovit, RV, Hao, MM, Croaker, DH, Furness, JB and Adams, CD: Surgical method to prevent early death of neonatal rat pups with Hirschsprung disease, thus permitting development of long-term therapeutic approaches. Biology Methods and Protocols 7, bpac004 (2022). doi.org/10.1093/biomethods/bpac004

2021

20. Di Natale MR, Stebbing, MJ, Furness, JB: Autonomic neuromuscular junctions. Autonomic Neurosci 234: 102816, 1-7 (2021). Doi: 10.1016/j.autneu.2021.102816
21. Diwakarla, S., McQuade, RM, Constable, R, Artaiz O, Enie Lei, E , Barnham KJ, Adlard, PA, Cherny, RA, Di Natale, MR, Hongyi Wu, H., Xin-yi Chai, X-Y, Lawson, VA, Finkelstein, DI, Furness, JB:  ATH434 reverses colorectal dysfunction in the A53T mouse model of Parkinson’s Disease  Journal of Parkinson’s Disease 11 1821–1832 (2021), DOI 10.3233/JPD-212731
22. Furness, JB, Pustovit, RV, Syder, AJ, Ringuet, MT, Yoo, EJ, Fanjul, A, Wykosky, J, Fothergill, LJ, Whitfield, EA, Furness, SGB:  Dopamine and ghrelin receptor co-expression and interaction in the spinal defecation centres.  Neurogast Motil 33, e14051 (2021) doi.org/10.1111/nmo.14051
23. Koo, A, Fothergill, LJ, Kuramoto, H, Furness, JB: 5-HT containing enteroendocrine cells characterised by morphologies, patterns of hormone co-expression, and relationships with nerve fibres in the mouse gastrointestinal tract.  Histochem Cell Biol 155: 623-636 (2021) doi.org/10.1007/s00418-021-01972-3
24. Kuramoto, H, Koo, A, Fothergill, LJ, Hunne, B, Yoshimura, R, Kadowaki, M, Furness, JB:  Morphologies and distributions of 5-HT containing enteroendocrine cells in the mouse large intestine.  Cell Tissue Res 384, 275–286 (2021).  DOI: 10.1007/s00441-020-03322-6
25. Populin, L, Stebbing, MJ, Furness, JB:  Neuronal regulation of the gut immune system and neuromodulation for treating inflammatory bowel disease.  FASEB Bioreviews 3, 953–966 (2021) doi.org/10.1096/fba.2021-00070
26. Pustovit RV, Zhang X-Z, Liew J, Praveen P, Liu M, Koo A, Oparija-Rogenmozere L, Ou Q, Kocan M, Nie S, Bathgate RAB, FurnessJBand Hossain MA.  A novel antagonist peptide reveals a physiological role of insulin-like peptide 5 in control of colorectal function.  ACS Pharmacol Translational Sci. 4, 1666-1674 (2021) doi.org/10.1021/acsptsci.1c00171.
27. Ringuet, MT*, Hunne, B*, Lenz, M., Bravo, DM, Furness, JB:  Analysis of the uptake and incorporation into tissues of dietary nanoelemental, organic and inorganic selenium.  Nutrients 13, 1073 (2021) doi.org/10.3390/nu13041073