The Walter and Eliza Hall Institute of Medical Research

Associate Professor Joan Heath

Details

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Division: Chemical Biology

Research Overview

Colon cancer is the second highest cause of cancer deaths in Australia after lung cancer. The lifetime risks of contracting colon cancer and dying from this disease are 1 in 10 and 1 in 30, respectively. The Heath laboratory is interested in identifying genes and biological pathways that govern intestinal development and colon cancer formation.

Colon cancers develop in the cellular lining (intestinal epithelium) of the large bowel. The over-arching premise of our work is that the rapidly developing zebrafish intestinal epithelium is an excellent model for colon tumour growth. This proposition stems from the fact that developing organs and cancer tissues exhibit several common behaviours, including rapid growth and proliferation, cell migration, blood vessel development and cell death. Due to their external development and optical transparency, zebrafish larvae provide an excellent model for studying these dynamic cellular processes in real time.

Over the last decade, we have discovered several genes that upon mutation disrupt the growth and development of the zebrafish intestinal epithelium. A large part of our research is now focused on determining whether the aberrant expression of these genes may contribute to the formation of colon cancer in mice and humans.

 

 

 

 

 

 

 

Animals in research: zebrafish

Joan Heath, The Conversation, 9 May 2013

Models of Transparency: Researchers are taking advantage of small, transparent zebrafish embryos and larvae to understand the development and spread of cancer

Joan K. Heath, David Langenau, Kirsten C. Sadler, and Richard White, The Scientist, 1 April 2013

 

Research Interests

• Role of U12-type splicing in development and cancer

• Role of Serine arginine splicing factors (SRSPs) in stem cell properties, development and cancer

• Screening for small molecules that inhibit mRNA splicing in cell lines and zebrafish

• Development of drug delivery vehicles targeted to colon cancer cells

 

Selected Publications

1. Boglev Y, Badrock AP, Trotter AJ, Du Q, Richardson EJ, Parslow AC, Markmiller SJ, Hall NE, de Jong-Curtain TA, Ng AY, Verkade H, Ober EA, Field HA, Shin D, Shin CH, Hannan KM, Hannan RD, Pearson RB, Kim SH, Ess KC, Lieschke GJ, Stainier DY, Heath JK. Autophagy induction is a tor- and tp53-independent cell survival response in a zebrafish model of disrupted ribosome biogenesis. PLoS Genet. 2013 Feb;9(2):e1003279. PMID: 23408911

2. Johnston AP, Kamphuis MM, Such GK, Scott AM, Nice EC, Heath JK, Caruso F. Targeting cancer cells: controlling the binding and internalization of antibody-functionalized capsules. ACS Nano. 2012 Aug 28;6(8):6667-74. PMID:22872125

3. Pase L, Layton JE, Wittmann C, Ellett F, Nowell CJ, Reyes-Aldasoro CC, Varma S, Rogers KL, Hall CJ, Keightley MC, Crosier PS, Grabher C, Heath JK, Renshaw SA, Lieschke GJ. Neutrophil-delivered myeloperoxidase dampens the hydrogen peroxide burst after tissue wounding in zebrafish. Curr Biol. 2012 Oct 9;22(19):1818-24. PMID:22940471

4. Heath JK. Transcriptional networks and signaling pathways that govern vertebrate intestinal development. Curr Top Dev Biol. 2010 90:159-92. Review. PMID:20691849

5. Buchert M, Athineos D, Abud HE, Burke ZD, Faux MC, Samuel MS, Jarnicki AG, Winbanks CE, Newton IP, Meniel VS, Suzuki H, Stacker SA, Näthke IS, Tosh D, Huelsken J, Clarke AR, Heath JK, Sansom OJ. Ernst M. Genetic dissection of differential signaling threshold requirements for the Wnt/beta-catenin pathway in vivo. PLoS Genet. 2010 Jan 15;6(1):e1000816. PMID: 20084116

6. Yan Y, Johnston AP, Dodds SJ, Kamphuis MM, Ferguson C, Parton RG, Nice EC, Heath JK, Caruso F. Uptake and intracellular fate of disulfide-bonded polymer hydrogel capsules for Doxorubicin delivery to colorectal cancer cells. ACS Nano. 2010 May 25;4(5):2928-36. PMID:20420377

7. Kamphuis MM, Johnston AP, Such GK, Dam HH, Evans RA, Scott AM, Nice EC, Heath JK, Caruso F. Targeting of cancer cells using click-functionalized polymer capsules. J Am Chem Soc. 2010 Nov 17;132(45):15881-3. PMID:20977221

8. de Jong-Curtain TA, Parslow AC, Trotter AJ, Hall NE, Verkade H, Tabone T, Christie EL, Crowhurst MO, Layton JE, Shepherd IT, Nixon SJ, Parton RG, Zon LI, Stainier DY, Lieschke GJ, Heath JK. Abnormal nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-deficient zebrafish. Gastroenterology. 2009 Mar;136(3):902-11. PMID: 19073184

9. Ng AN, de Jong-Curtain TA, Mawdsley DJ, White SJ, Shin J, Appel B, Dong PD, Stainier DY, Heath JK. Formation of the digestive system in zebrafish: III. Intestinal epithelium morphogenesis. Dev Biol. 2005 Oct 1;286(1):114-35. PMID:16125164

10. Tebbutt NC, Giraud AS, Inglese M, Jenkins BJ, Waring PM, Clay FJ, Malki S, Grail D, Hollande F, Heath JK, Ernst M. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nature Medicine 2002 Oct;8(10):1089-97. PMID:12219085

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Current Laboratory Members

Laboratory Head: Joan Heath BA(Hons) Cantab MA Cantab PhD CNAA

Senior Postdoctoral Fellow: Minni Anko MSc Turku PhD Abo Akademi University

Postdoctoral Fellow: Karen Doggett BSc(Hons) Surrey DPhil Oxon

Postdoctoral Fellow: Ben Williams BSc(Hons) UNSW PhD Melb

Research Assistant: Tanya de Jong-Curtain BA Monash BSc(Hons) Monash PhD Melb

Research Assistant: Janine Coates BSc(Hons) Monash

Research Assistant: Dora McPhee BSc(Hons) Monash

Research Assistant: Andrea Aprico BSc (Hons) Monash

Research Assistant: Lotta Burstroem MSc Stockholm

Research Assistant: Julia Griesbach MSc Gottingen

Research Assistant: Johanna Simkin BSc (Hons) Melb

Aquarium Manager, Tyson Blanch

Aquarium Technician: Lysandra Richards DipAnimTech NMIT