Elizabeth Vincan

• Elizabeth Vincan

  Professor

  evincan@unimelb.edu.au
  9342 9348

Research Overview

Professor Elizabeth Vincan is a Professorial Medical Scientist at the Victorian Infectious Diseases Reference Laboratory (VIDRL) and Professor and Head of the Host Pathogen Interactions (HPI) laboratory in the Department of Infectious Diseases, University of Melbourne. Her role as Medical Scientist is to translate research discoveries from her research laboratory into a clinical setting. Elizabeth is an Adjunct Professor within the Curtin School of Medicine, Curtin University, Perth, Western Australia; a Clinical Scientist, Fellow of the Australian Institute of Medical and Clinical Scientists (AIMS); and a founding member of the Australian Living Organoid Alliance (ALOA).

Elizabeth completed her PhD at the University of Melbourne in 1995. Her experimental work, conducted at Fairfield Infectious Diseases Hospital, identified and characterised novel macrophage tropic HIV isolates. Her postdoctorals at the Baker Institute and Peter MacCallum Cancer Centre led to a keen interest in signal transduction and her lab's research focus: the Wnt signalling pathway in cancer. She is internationally recognised as an expert in Wnt signalling and was the convenor of the first international Wnt meeting, and the first EMBO workshop, held in Australia (Cable Beach, Broome, 2014). Her research team has attracted numerous competitive grants and awards, with almost continuous NHMRC funding since 2009.

Elizabeth’s group demonstrated inhibiting Wnt has potent anti-cancer effects, providing novel avenues to block cancer growth. Her research team used powerful transgenic mouse models and innovative three-dimensional (3D) organoid models to identify a pivotal role for a Wnt receptor, Frizzled-7, in tissue stem cells and cancer. The organoid models are now being adopted to model infectious disease. Since COVID-19, host pathogen interactions has become a focus of her research laboratory.

Organoids: Avatars of infectious disease

Elizabeth Vincan Project A – tissue stem cell derived organoids.

Adult stem cells are tissue restricted and self-assemble into mini-replicas of their tissue of origin. Consequently, stem cells present in tissue fragments can recapitulate key characteristics and function of organs in a dish when provided with a 3D environment and the necessary growth factors. Organoids (meaning organ-like) were adopted globally during the COVID-19 pandemic, once it was recognised that conventional cell lines used by virologists since the 1960’s did not recapitulate SARS-CoV-2 infection in humans. We established a human nose epithelium organoid – based neutralisation assay for SARS-CoV-2, which proved to be a discerning neutralization assay. We now aim to establish/adopt 3D organoid models to represent the main organs targeted by human pathogens – brain, respiratory tract, gut and liver. Through the Australian Donation and Transplantation Biobank (ADTB) at Austin health, established by Dr Claire Gordon, we have access to all tissues required, except brain.

Elizabeth Vincan Project B – pluripotent stem cell derived organoids.

Brain tissue is less readily available through routine surgery and is not routinely collected by ADTB. We collaborate with scientists at the Murdoch Children’s Research Institute (MCRI) and the Australian Organoid Facility (AOF) at University of Queensland to establish pluripotent stem cell derived brain organoids. Furthermore, in collaboration with the Victorian Centre for Functional Genomics (VCFG) at the Peter MacCallum Cancer Centre Parkville and the AOF, we are establishing high-throughput, high-content imaging of 3D organoid models.

Once the organoid models are established, be it tissue stem cell or pluripotent stem cell derived, they will be made available for research and tissue culture-based diagnostics on a cost recovery basis.

Staff

• Professor Elizabeth Vincan, Clinical Scientist & Laboratory Head
• Dr Hoanh Tran, Senior Research Fellow/Co-Laboratory Head, HPI
• Dr Bang Manh Tran, Research Fellow
• Dr Sarah Harbach, Research Fellow (Honorary)
• Dr George Kastrappis, Research Fellow
• Jean Moselen, Research Assistant (Casual)
• Dr Toby Phesse, Senior Research Fellow (Honorary)

Funding

• Cummings Centre for Pandemic Therapeutics (CGCPT, R1)
  CGCPT00007 (2024-2026, $600,000) E Vincan
  “Human Organoids: innovative, authentic models of infection”
• Victorian Medical Research Accelerated Fund (VMRAF, R5)
  GA-F3744277-2925 (2022-2024, $200,000) E Vincan
  “Establishment of tissue culture methods for SARS-CoV-2 propagation that ensure working stocks reflect the pathogenicity and genetic composition of circulation global clades”
• NHMRC Ideas
  APP1181580 (2020-2024, $1,003,600) E Vincan (CIA), H Tran (CIB), BM Tran (CIC), TJ Phesse (CID), H Clevers (CIE)
  “Adult stem cell-derived organoids: innovative models to elucidate signalling mechanisms in Wnt-addicted cancers”
• NHMRC Project
  APP1099302 (2016-2018, $732,008) E Vincan (CIA), TJ Phesse (CIB), N Barker (CIC)
  “Fzd7 as a therapeutic target for gastric cancer”
• NHMRC Project
  566679 (2009-2011, $640,950) E Vincan (CIA), N Barker (CIB), H Clevers (CIC), T Brabletz (CID)
  “Molecules involved in gut development and bowel cancer”

Research Publications

1. Vincan E. Frizzled/Wnt Signalling: The Insidious Promoter of Tumour Growth and Progression. Front Biosci9:1023-1034 (2004) Review
2. Vincan E and Barker N. The upstream components of the Wnt signalling pathway control the dynamic EMT and MET associated with colorectal cancer progression. Clin Exp Metastasis 25:657-63 (2008) Review
3. Flanagan DJ, Phesse TJ, Barker N, Schwab RHM, Amin N, Malaterre J, Stange DE, Nowell CJ, Currie SA, Saw JT, Beuchert E, Ramsay RG, Sansom O, Ernst M, Clevers H and Vincan E. Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5+ stem cells. Stem Cell Reports 4:759-67 (2015)
4. Flanagan DJ, Barker N, Di Costanzo N, Mason E, Gurney A, Meniel V, Koushyar S, Austin CR, Ernst M, Pearson HB, Boussioutas A, Clevers H, Phesse TJ, Vincan E. Frizzled-7 is required for Wnt signalling in gastric tumours with and without Apc mutations. Cancer Research 79:970-981 (2019)
5. Flanagan DJ, Vincan E, Phesse TJ. Wnt signaling in cancer: not a binary ON:OFF switch. Cancer Research 79:5901-5906 (2019) Review
6. Tran BM, Flanagan DJ, Ebert G, Warner N, Tran H, Fifis T, Kasptrappis G, Christophi C, Pellegrini M, Torresi J, Phesse TJ and Vincan E. The hepatitis B virus pre-core protein p22 activates Wnt signaling. Cancers 12:1435 (2020)
7. Collett S, Torresi J, Earnest-Silveira L, Khanh Truong V, Christiansen D, Tran BM, VINCAN E, Ramsland PA, Elbourne A. Investigating virus-host cell interactions: Comparative binding forces between hepatitis C virus-like particles and host cell receptors in 2D and 3D cell culture models. J Colloid and Interface Science 592:371-384 (2021)
8. Tran BM, Flanagan DJ, Phesse TJ, Vincan E. Frizzled7 Activates β-Catenin-Dependent and β-Catenin-Independent Wnt Signalling Pathways During Developmental Morphogenesis: Implications for Therapeutic Targeting in Colorectal Cancer (in Pharmacology of the Wnt Signaling System, Editors Gunnar Schulte & Pawel Kozielewicz) Handbook of Experimental Pharmacology 269:251-277 (2021) Book Chapter
9. Tran BM, Grimley SL, McAuley JL, Hachani A, Ernest L, Wong SL, Caly L, Druce J, Purcell DFJ, Jackson DC, Catton M, Nowell CJ, Leonie L, Deliyannis G, Waters SA, Torresi J, Vincan E. Air-Liquid-Interface differentiated human nose epithelium: a robust primary tissue culture model of SARS-CoV-2 infection. Int J Molecular Sciences 23:835 (2022)
10. Tran BM, Deliyannis G, Hachani A, Ernest L, Torresi J, Vincan E. Organoid Models of SARS-CoV-2 infection: What Have We Learned About COVID-19? Organoids 1:2-27 (2022) Review
11. Preston SP, Stutz MD, Allison CC, Nachbur U, Gouil Q, Tran BM, Duvivier V, Arandjelovic P, Cooney JP, Mackiewicz L, Meng Y, Schaefer J, Bader SM, Peng H, Valaydon Z, Rajasekaran P, Jennison C, Lopaticki S, Farrell A, Ryan M, Howell J, Croagh C, Karunakaran D, Schuster-Klein C, Murphy JM, Fifis T, Christophi C, Vincan E, Blewitt ME, Thompson A, Boddey JA, Doerflinger M and Pellegrini M. Epigenetic Silencing of RIPK3 in Hepatocytes Prevents MLKL-mediated Necroptosis From Contributing to Liver Pathologies. Gastroenterology 163:1643-1657 (2022)
12. McAuley AJ, Jansen van Vuren P, Mohammed M, Faheem F, Goldie S, Riddell S, Gödde NJ, Styles IK, Bruce MP, Chahal S, Keating S, Blasdell KR, Tachedjian M, O'Brien CM, Singanallur NB, Viana JN, Vashi AV, Kirkpatrick CM, MacRaild CA, Shah RM, Vincan E, Athan E, Creek DJ, Trevaskis NL, Murugesan S, Kumar A, Vasan SS. Use of Human Lung Tissue Models for Screening of Drugs Against SARS-CoV-2 Infection. Viruses 14:2417 (2022)
13. Deliyannis G, Gherardin NA, Wong CY, Grimley SL, Cooney JP, Redmond SJ, Ellenberg P, Davidson KC, Mordant FL, T, Smith T, Gillard M, Lopez E, McAuley J, Tan CW, Wang JJ, Zeng W, Littlejohn M, Zhou R, Chan JFW, Chen ZW, Hartwig AE, Bowen R, Mackenzie JM, VINCAN E, Torresi J, Kedzierska K, Pouton CW, Gordon TP, Wang LF, Kent SJ, Wheatley AK, Lewin SR, Subbarao K, Chung AW, Pellegrini M, Munro T, Nolan T, Rockman S, Jackson DC, Purcell DFJ, Godfrey DI. Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine. eBioMedicine 92:104574 (2023)
14. Westhaus A, Cabanes-Creus M, Dilworth KL, Zhu E, Gómez DS, Navarro RG, Amaya AK, Scott S, Kwiatek M, McCorkindale AL, Hayman TE, Frahm S, Perocheau DP, Tran BM, VINCAN E, Wong SL, Waters SA, Riddiough GE, Perini MV, Wilson LOW, Baruteau J, Diecke S, González-Aseguinolaza G, Santilli G, Thrasher AJ, Alexander IE, Lisowski L.  Assessment of pre-clinical liver models based on their ability to predict the liver-tropism of AAV vectors. Human Gene Therapy 34:273-288 (2023)
15. Quah PS, Tran BM, Corbin VDA, Wong CY, Mendez AD, Hartley CA, Zeng W, Chang JJ-Y, Hanssen E, Trifunovic Z, Reading P, Jackson DC, Vincan E, Coin LJM, and Deliyannis G. Modelling Bovine Respiratory Disease in Tracheal Epithelium Organoids Embedded in Matrix. Organoids 2:82-101 (2023)
16. Vincan E. Organoids Are Us. Organoids 2:120-122 (2023) Editorial
17. Lim CK, Ornella R, Tran BM, Flanagan DJ, Kirby EN, McCartney EM, Tse E, VINCAN E, Beard MR. Assessment of hepatitis virus infection and interhost cellular responses using intrahepatic cholangiocyte organoids. J Medical Virology 95:e29232 (2023)
18. Frank D, Bergamasco M, Mlodzianoski M, Kueh A, Tsui E, Hall C, Kastrappis G, Voss AK, McLean C, Faux M, Rogers K, Tran BM, Vincan E, Komander D, Dewson G, Tran H. Trabid patient mutations impede the axonal trafficking of adenomatous polyposis coli to disrupt neurite growth. eLife 2023, 12
19. Montoya JC, Simon Collett S, Ruiz DF, Earnest L, Edeling MA, Yap ASH, Wong CY, Cooney JP, Davidson KC, Roberts J, Rockman S, Tran BM, McAuley JL, Deliyannis G, Grimley SL, Purcell DFJ, Waters SA, Godfrey DI, Hans D, Pellegrini M, Mackenzie JM, Vincan E, Heath WR, Torresi J. SARS-CoV-2 Virus-Like Particle Vaccine Protection in Mice Correlates with Neutralizing Antibody in Air-Liquid-Interface Differentiated Human Nasal Epithelium. Organoids 3(1):18-31 (2024) Published 1 Feb 2024 - https://doi.org/10.3390/organoids3010002 (2023)
20. Chang JJ-Y, Grimley SL, Tran BM, Deliyannis G, Tumpach C, Stinear TP, Pitt ME, VINCAN E and Coin LJM. Uncovering strain- and age- dependent differences in innate immune response to SARS-CoV-2 infection in nasal epithelia using combined short and long-read csRNA-seq. iSCIENCE 2024 Published online 14/5/24; https://doi.org/10.1016/j.isci.2024.110009