Dr Helen Abud - Researcher Profile

Dr Helen Abud

Address

Dept of Anatomy & Developmental Biology
Faculty of Medicine, Nursing & Health Sciences, Clayton

Biography

Life in the balance – stemming intestinal disease and bowel cancer  

Dr Helen Abud studies the delicate balancing act that goes on in our intestine, where stem cells help replace our intestinal lining every few days. Overactive stem cells here can lead to bowel cancer and underactive cells to a loss of intestinal lining. Helen is trying to stop these cells causing damage and use them to repair it.

Our intestine helps us extract nutrients from food and get rid of the waste. To do this effectively, large numbers of cells in our intestinal lining die in the process to be replaced by new cells, created from stem cells present before birth.

Trained as a developmental biologist, Helen is fascinated by this process. 

“Blood and skin renew constantly, but not quite at the rate of the intestinal lining.” Helen says, “So, if you’re interested in developmental pathways, as I am, then the intestine is a great organ to study.”

Helen says a healthy intestine requires the right balance between dying and renewing cells. Too many new cells can lead to tumours and bowel cancer, the number two cause of cancer deaths in Australia.

Too few new cells can denude the intestinal lining and cause painful inflammation and ulcerations, which can happen after infections or cancer treatment, such as chemotherapy or radiotherapy.

It can also happen in the 10 per cent of premature babies who get necrotising entrocolitis, often treated by removing large sections of the bowel, leaving some of them unable to draw enough nutrition from ingested food.

Bowel cancer patients who undergo surgery and accident victims with injured intestines face similar problems, since intestinal tissue dies quickly if the blood supply is interrupted.

Helen is trying to identify the pathways that control intestinal stem cell production in the hope of identifying targets for future treatments.

“All cells reproduce by dividing, and many traditional cancer treatments affect all dividing cells, which is why you get side effects,” Helen says. “They are far too broad.”

When intestinal stem cells divide, some ‘differentiate’ and become intestinal lining cells and some remain undifferentiated ‘daughter’ stem cells, from which the next generation of lining cells and daughter stem cells will come.

“If too many undifferentiated stem cells are made,” Helen says, “you may end up with a tumour, and if you don’t get enough, you’re going to lose your intestinal lining eventually.”

Helen says her team has identified a molecule involved in this process, which, if removed, results in all the stem cells differentiating without producing daughter stem cells.

Perhaps more remarkably, she says her research may help identify cancer stem cells that produce cancerous tumours and daughter cells for future tumours.

If found, they would give developers of future bowel cancer treatments clear targets to ensure tumours never return, especially the most aggressive kind.

Helen is collaborating with doctors led by Associate Professor Paul McMurrick from Cabrini Hospital to see if particular markers correlate to particular tumours, allowing them to be graded according to severity.

“We’re hoping that our research will eventually allow a surgeon to remove a tumour and test it against a panel of markers that will indicate the most likely outcome and the best treatment.”

Helen is also trying to understand if a patient’s stem cells could repair an intestine by either stimulating them to regenerate more efficiently in the body or by taking tissue samples to increase their number in culture before returning them.

She’s working with scientist and paediatric surgeon Professor Wei Cheng at the Monash Medical Centre to grow tissue in culture to identify factors that might stimulate repairs.

“This is not pie-in-the-sky stuff because we have quite good candidates. We haven’t got to the point of showing repair, but we know the effects of some of the growth factors in cultures, and we’re only just starting the work.”

Related Links:

  • Epithelial Regeneration Laboratory

Keywords

epithelial, intestine, epithelium,

Qualifications

GRADUATE CERTIFICATE IN HIGHER EDUCATION
Institution: Monash University
Year awarded: 2009
DOCTOR OF PHILOSOPHY
Institution: Oxford
Year awarded: 1995
BACHELOR OF SCIENCE ( HONOURS )
Institution: University of Melbourne
Year awarded: 1986

Publications

Book Chapters

Abud, H.E., Young, H.M., Newgreen, D.F., 2008, Analysing tissue and gene function in intestinal organ culture, in Methods in Molecular Biology, Wnt Signaling, eds E Vincan, Humana Press, USA, pp. 275-286.

Journal Articles

Caruana, G., Farlie, P.G., Hart, A.H., Bagheri-Fam, S., Wallace, M.J., Dobbie, M.S., Gordon, C.T., Miller, K.A., Whittle, B., Abud, H.E., Arkell, R.M., Cole, T.J., Harley, V.R., Smyth, I.M., Bertram, J.F., 2013, Genome-Wide ENU Mutagenesis in Combination with High Density SNP Analysis and Exome Sequencing Provides Rapid Identification of Novel Mouse Models of Developmental Disease, PLoS ONE [P], vol 8, issue 3, Public Library of Science, USA, pp. 1-13.

Liang, R., Hinds, R.M., Abud, H.E., Cheng, W., 2013, Hedgehog signalling is downregulated in celiac disease, Canadian Journal of Gastroenterology [P], vol 27, issue 1, PULSUS GROUP INC, CANADA, pp. 5-7.

Monk, A.C., Abud, H.E., Hime, G.R., 2012, Dmp53 is sequestered to nuclear bodies in spermatogonia of Drosophila melanogaster , Cell And Tissue Research [P], vol 350, issue 2, Springer, Germany, pp. 385-394.

Liang, R., Morris, P., Cho, S., Abud, H.E., Jin, X., Cheng, W., 2012, Hedgehog signaling displays a biphasic expression pattern during intestinal injury and repair, Journal of Pediatric Surgery [P], vol 47, W B SAUNDERS CO-ELSEVIER INC, UNITED STATES, pp. 2251-2263.

Buchert, M., Athineos, D., Abud, H.E., Burke, Z.D., Faux, M.C., Samuel, M.S., Jarnicki, A.G., Winbanks, C.E., Newton, I.P., Meniel, V.S., Suzuki, H., Stacker, S.A., Nathke, I.S., Tosh, D., Huelsken, J., Clarke, A.R., Heath, J.K., Sansom, O.J., Ernst, M., 2010, Genetic dissection of differential signaling threshold requirements for the Wnt/beta-catenin pathway in vivo, Plos Genetics [P], vol 6, issue 1 (e1000816), Public Library of Science, USA, pp. 1-13.

Horvay, K., Casagranda, F., Gany, A., Hime, G.R., Abud, H.E., 2010, Wnt signaling regulates Snai1 expression and cellular localization in the mouse intestinal epithelial stem cell niche, Stem Cells and Development [P], vol 20, Mary Ann Liebert, Inc. Publishers, USA, pp. 737-745.

Martinez, G., Wijesinghe, M., Turner, K., Abud, H.E., Taketo, M.M., Noda, T., Robinson, M.L., de Iongh, R.U., 2009, Conditional mutations of beta-Catenin and APC reveal roles for canonical Wnt signaling in lens differentiation, Investigative Ophthalmology and Visual Science [P], vol 50, issue 10, Association for Research in Vision and Ophthalmology, USA, pp. 4794-4806.

Cain, S., Martinez, G., Kokkinos, M.I., Turner, K., Richardson, R.J., Abud, H.E., Huelsken, J., Robinson, M.L., de Iongh, R.U., 2008, Differential requirement for beta-catenin in epithelial and fiber cells during lens development, Developmental Biology, vol 321, issue 2, Academic Press, USA, pp. 420-433.

Hime, G.R., Loveland, K.A.L., Abud, H.E., 2007, Drosophila spermatogenesis: insights into testicular cancer, International Journal of Andrology, vol 30, issue 4, Blackwell Publishing, Denmark, pp. 265-274.

Abud, H.E., Layton, M.J., 2006, Growing a gut in a petri dish, Australasian Science, vol 27, issue 8, Control Publications, Australia, pp. 26-28.

de Iongh, R.U., Abud, H.E., Hime, G.R., 2006, WNT/Frizzled signaling in eye development and disease, Frontiers in Bioscience, vol 11, issue 1, Frontiers in Bioscience, Inc., Manhassett USA, pp. 2442-2464.

Abud, H.E., Watson, N., Heath, J.K., 2005, Growth of intestinal epithelium in organ culture is dependent on EGF signalling, Experimental Cell Research, vol 303, issue 2, Elsevier, Inc., San Diego USA, pp. 252-262.

Abud, H.E., Lock, P., Heath, J.K., 2004, Efficient gene transfer into the epithelial cell layer of embryonic mouse intestine using low-voltage electroporation, Gastroenterology, vol 126, issue 7, WB Saunders Co-Elsevier Inc, Philadelphia USA, pp. 1779-1787.

Abud, H.E., Heath, J.K., 2004, Letter to the editor: detecting apoptosis during the formation of polarized intestinal epithelium in organ culture, Cell Death and Differentiation, vol 11, issue 7, Nature Publishing Group, London England, pp. 788-789.

Abud, H.E., 2004, News and commentary: shaping developing tissues by apoptosis, Cell Death and Differentiation, vol 11, issue 8, Nature Publishing Group, London England, pp. 797-799.

Hime, G.R., Bunt, S., Abud, H.E., 2003, Different daughters: regulation of asymmetric cell division, Australian Biochemist, vol 34, issue 1, H & K Printers, Caulfield South Vic Australia, pp. 10-13.

Bueno, D., Abud, H.E., Skinner, J., Heath, J.K., 2001, Constitutive expression of FGF4 disrupts the development of the eye and the anterior CNS during mouse embryogenesis, but does not influence the expression of shh in these areas, Belgian Journal of Zoology, vol 131, issue 1, Societe Royale Zoologique de Belgique, Diepenbeek Belgium, pp. 57-62.

Hime, G.R., Abud, H.E., Garner, B., Harris, K., Robertson, H., 2001, Dynamic expression of alternate splice forms of D-cbl during embryogenesis, Mechanisms of Development, vol 102, issue 1, Elsevier Science BV, Amsterdam The Netherlands, pp. 235-238.

Ford-Perriss, M., Abud, H.E., Murphy, M., 2001, Fibroblast growth factors in the developing central nervous system, Clinical and Experimental Pharmacology and Physiology, vol 28, issue 7, Blackwell Publishing, Oxford England, pp. 493-503.

Grants

Title:
Aperio ScanScope AT (Digital slide scanner) with operating software and web-based SpectrumTM server license for an unlimited number of digital images.
Investigators:
O'Bryan, M, Furic, L, Risbridger, G, Bertram, J, Lieschke, G, Smyth, I, Watkins, D, Cole, T, McMenamin, P, Abud, H, Loveland, K
Funding:
(2012 - 2016). National Health & Medical Research Council (NHMRC).
Title:
Building an intestine: development and regeneration of the epithelium.
Investigators:
Abud, H, Barker, N
Funding:
(2011 - 2015). National Health & Medical Research Council (NHMRC).
Title:
Olympus MVX10 Macroview Microscope with DP72 digital camera andn imaging system.
Investigators:
Lieschke, G, O'Bryan, M, Loveland, K, Heng, J, McMenamin, P, Abud, H, Bourne, J, Verkade, H, Kaslin, V, Rosenthal, N
Funding:
(2011 - 2015). National Health & Medical Research Council (NHMRC).
Title:
The Impact of Wnt Signaling on Spermatogenesis.
Investigators:
Loveland, K, Abud, H
Funding:
(2011 - 2015). National Health & Medical Research Council (NHMRC).
Title:
The role of Snail family proteins in stem cells and tumour growth.
Investigators:
Abud, H, Hime, G, Somers, W
Funding:
(2008 - 2012). National Health & Medical Research Council (NHMRC).
Title:
The role of snail family proteins in male fertility and testicular cancer.
Investigators:
Loveland, K, Abud, H, Hime, G
Funding:
(2013 - 2017). National Health & Medical Research Council (NHMRC).
Title:
Functional studies on the role of DNp73 in stem cells and cancer.
Investigators:
Abud, H, Hime, G, Stiewe, T, McMurrick, P
Funding:
(2011 - 2015). National Health & Medical Research Council (NHMRC).
(2011 - 2015). The University of Melbourne.
Title:
APC mutation and initiation of colorectal cancer.
Investigators:
Abud, H
Funding:
(2007 - 2011). National Health & Medical Research Council (NHMRC).

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Functional analysis of DNp73 in the intestinal stem cell niche.
Supervisors:
Abud, H (Main).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
The importance of wnt signalling in male germ cell development.
Supervisors:
Abud, H (Joint-co), Loveland, K (Joint).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
The role of Snai1 in regulating the maintenance and proliferation of intestinal stem cells.
Supervisors:
Abud, H (Main), Horvay, K (Associate).
Program of Study:
(POSTGRADUATE QUALIFYING OR PRELIMINARY).
Thesis Title:
Wnt signalling in spermatogenesis and testicular cancer.
Supervisors:
Loveland, K (Main), Abud, H (Associate).

Completed Supervision

Student:
Kass, L.
Program of Study:
Role of transcription factors in regulation of the intestinal stem cell niche. 2009.
Supervisors:
Abud, H (Main).