Research in the Heath laboratory is influenced by the recognition that many of the dynamic processes that occur during development are also highly active or dysregulated in cancer, such as cell proliferation, differentiation, migration, angiogenesis, and apoptosis. By participating in a forward genetic screen in zebrafish, Heath lab members identified a collection of genes that are critical for the rapid expansion of the digestive organs (liver, pancreas and intestine) during zebrafish larval development.

We are now investigating whether the decreased expression of these genes, and the cellular processes they are involved in, can arrest the growth of lung, liver, stomach and colon cancer. Our current studies are focused on identifying small molecule inhibitors of these processes for the purpose of cancer therapy.


Selected publications from Prof Joan Heath

Morgan KJ, Doggett K, Geng F, Mieruszynski S, Whitehead L, Smith KA, Hogan BM, Simons C, Baillie GJ, Molania R, Papenfuss AT, Hall TE, Ober EA, Stainier DYR, Gong Z, Heath JK. ahctf1 and kras mutations combine to amplify oncogenic stress and restrict liver overgrowth in a zebrafish model of hepatocellular carcinoma. Elife. 2023 Jan 17;12:e73407. doi: 10.7554/eLife.73407. PMID: 36648336

Doggett K, Morgan KJ, Mieruszynski S, Williams BB, Olthof AM, Garnham AL; Milevskiy MJG, Whitehead L, Coates J, Buchert M, Robert JJ O’Donoghue RJJ, Hall TE, Gong Z, Putoczki TL, Ernst M, Sutherland KD, Kanadia RN, Heath JK. The minor spliceosome offers a therapeutically viable target for the treatment of a broad spectrum of cancers. BioRxiv 2021 doi: https://doi.org/10.1101/2021.12.09.469623

Olthof AM, White AK , Mieruszynski S, Doggett K, Lee MF , Chakroun A , Abdel Aleem AK, Rousseau J, Magnani C, Roifman CM, Campeau PM, Heath JK, Kanadia RN. Disruption of exon-bridging interactions between the minor and major spliceosomes results in alternative splicing around minor introns. Nucleic Acids Research 49 (6), 3524-3545. PMID: 33660780

Doggett K, Williams BB, Markmiller S, Geng FS, Coates J, Mieruszynski S, Ernst M, Thomas T, Heath JK. Early developmental arrest and impaired gastrointestinal homeostasis in U12-dependent splicing-defective Rnpc3-deficient mice. RNA 2018:24 1856-1870. PMID: 30254136

Kim EJY, Anko ML, Flensberg C, Majewski IJ, Geng FS, Firas J, Huang DCS, van Delft MF, Heath JK. BAK/BAX-mediated apoptosis is a Myc-induced roadblock to reprogramming. Stem Cell Reports. 2018 Jan 17. pii: S2213-6711(17)30567-2. doi: 10.1016/j.stemcr.2017.12.019. PMID: 29358089

Lobert VH, Mouradov D, Heath JK. Focusing the spotlight on the zebrafish intestine to illuminate mechanisms of colorectal cancer. Adv Exp Med Biol. 2016;916:411-37. doi: 10.1007/978-3-319-30654-4_18. Review. PMID: 27165364

Williams BB, Tebbutt NC, Buchert M, Putoczki TL, Doggett K, Bao S, Johnstone CN, Masson F, Hollande F, Burgess AW, Scott AM, Ernst M, Heath JK. Glycoprotein A33 deficiency: a new mouse model of impaired intestinal epithelial barrier function and inflammatory disease. Dis Model Mech. 2015 Aug 1;8(8):805-15. PMID: 26035389

Markmiller S, Cloonan N, Lardelli RM, Doggett K, Keightley MC, Boglev Y, Trotter AJ, Ng AY, Wilkins SJ, Verkade H, Ober EA, Field HA, Grimmond SM, Lieschke GJ, Stainier DY, Heath JK. Minor class splicing shapes the zebrafish transcriptome during development. Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):3062-7. PMID: 24516132

Putoczki TL, Thiem S, Loving A, Busuttil RA, Wilson NJ, Ziegler PK, Nguyen P, Preaudet A, Farid R, Edwards K, Boglev Y, Luwor RB, Jarnicki A, Horst D, Boussioutas A, Heath JK, Sieber OM, Pleines I, Kile BJ, Nash A, Greten FR, McKenzie BS, Ernst M. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell 2013 Aug 12;24(2):257-71. PMID: 23948300

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

Lab research projects

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