|
|
Dr Rachel Gibson
BHSc(Hons) University of Adelaide
PhD, University of Adelaide
e-mail: rachel.gibson@adelaide.edu.au
Current Research Interests
Dr Rachel Gibson studies the effects of cytotoxic agents on the gastrointestinal
tract with the focus of her recent research being chemotherapy-induced mucositis.
Her research into oral mucositis detailed for the first time the time course
of cellular events that occur in humans following chemotherapy. As a consequence
of this research she was awarded a Cancer Council South Australia Post-Doctoral
Research Fellowship. More recently, Rachel has been investigating mechanisms
of chemotherapy-induced diarrhoea (a particularly nasty side effect from cancer
treatment). Rachel has recently been appointed a Lecturer within the Discipline
of Anatomical Sciences.
Rachel is member of the Multinational Association for Supportive Care in Cancer,
International Mucositis Study Group, International Dysphagia Study Group, Clinical
Oncology Society of Australia and the Australian Society for Medical Research.
She is on the Scientific Organising Committee for the South Australian State
Branch Local Scientific Meeting for the ASMR. Rachel has supervised 4 honours
students (3 First Class; 1 Second Class) and is currently supervising 3 PhD
Students, two of whom have been awarded NH&MRC Scholarships. In addition
Rachel has supervised various undergraduate research projects for BHSc and BSc
students. Since 2002 Rachel has published 34 papers, with a further 13 manuscripts
either submitted or in the final stages of preparation (for full list of publications
see attachment).
Possible Honours/PhD Projects
1. Targeted Therapies for Cancer and the Gastrointestinal Tract
In recent years, the use of targeted anti-cancer therapies as a treatment for
cancer, either by themselves or in conjunction with cytotoxic chemotherapy or
radiotherapy, has increased markedly. The main classes of targeted therapies
are monoclonal antibodies and small molecules. Although the therapeutic use
of targeted therapies for cancer has been highly effective in slowing disease
progression and improving disease-free survival, they have also been shown to
cause mucositis. Mucositis is the damage caused by chemotherapy, radiotherapy
and targeted therapies to mucous membranes of the alimentary tract (AT). Furthermore,
this damage causes pain and ulceration, vomiting, bloating and diarrhoea, depending
on the area of the AT affected. Mucositis impairs patients' quality of life
and threatens the effectiveness of the anticancer treatment in that it is dose
limiting. Moreover, targeted therapy drugs have the potential to cause mucositis
because they are not solely active on malignant cells but can cross-react with
receptors in other parts of the body. Furthermore, the AT has been identified
as a major site of targeted therapy-induced toxicity. The aim of this proposed
project is to further understand how targeted therapies cause mucositis. Students
will be exposed to a wide range of techniques including: a retrospective clinical
case study of targeted therapies, cell culture, immunocytochemistry, western
blotting and real-time PCR.
References:
1. Gibson RJ & Keefe DMK (2006) Cancer chemotherapy-induced diarrhoea
and constipation: mechanisms of damage and prevention strategies. Supportive
Care in Cancer; 14(9): 890-900.
2. Keefe DMK & Gibson RJ (2007) Mucosal injury from targeted anticancer
therapy. Supportive Care in Cancer; 15(5): 483-490.
2. Investigation of chemotherapy-induced changes to mucin expression in the
rat gastrointestinal tract
The normal microflora of the gastrointestinal tract (GIT) is a highly complex
ecosystem consisting of both aerobic and anaerobic bacteria. The gastrointestinal
microflora has a number of key functions including protection and metabolism
of: bilirubin, intestinal mucins, pancreatic enzymes, fatty acids, bile acids,
cholesterol and steroid hormones. Other functions of the gastrointestinal bacteria
include nutrient processing, regulation of intestinal angiogenesis and immune
functions. The gastrointestinal microflora and mucins are known to be affected
by chemotherapy and may be important factors in determining the severity of
chemotherapy-induced diarrhoea and mucositis. Unfortunately, it is not yet known
how these factors fit into the model of alimentary mucositis. Therefore by understanding
the role of the gastrointestinal microflora and mucins in the development of
chemotherapy-induced diarrhoea, these could become future therapeutic targets
for mucositis treatment, by altering microflora with antibiotics or probiotics,
or targeting the pathways involved in mucin gene expression. The aim of the
present study is to determine the time course of changes in gastrointestinal
microflora, mucin composition and distribution following methotrexate treatment
in the DA rat. Students will be exposed to a wide variety of techniques including:
real time PCR, immunohistochemistry, microbiological techniques, and histopathological
staining.
References:
1. Stringer AM, Gibson RJ, Logan RM, Bowen JM, Yeoh ASJ, Burns J & Keefe
DM (2007). Chemotherapy-induced diarrhoea is associated with changes in the
luminal environment in the DA rat, Experimental Biology & Medicine, 232(1):96-107.
2. Stringer AM, Gibson RJ, Logan RM, Bowen JM, Yeoh ASJ, & Keefe DM (2007).
Chemotherapy-induced mucositis: the role of gastrointestinal microflora and
mucins in the luminal environment, Journal of Supportive Oncology, (in press).
3. Gibson RJ & Keefe DMK (2006). Cancer chemotherapy-induced diarrhoea
and constipation: mechanisms of damage and prevention strategies, Supportive
Care in Cancer, 14(9): 890-900.
3. Chemotherapy-induced changes in the tongue
Mucositis of the oral cavity is reported as the most unpleasant side effect
of cancer treatment for patients. During very severe mucositis, ulcers develop
on the tongue which makes alimentation impossible, interferes with speaking
and swallowing and is extremely painful. It is very costly to manage patients
with severe oral mucositis, and there is currently very limited options for
prevention and treatment. The events leading up to ulceration have been described
in the mucositis pathobiology model, but to date, the time course of changes
that occurs in the tongue remains uncertain. The aim of this study is to conduct
a detailed time course analysis of changes that occur to the tongue following
different chemotherapeutic agents, including 5-Fluouracil, Methotrexate and
Irinotecan. Students will be exposed to immunohistochemistry, routine histological
and histopathological techniques, and TUNEL assays
References
1. Logan, R.M., Bowen, J.M., Stringer, A.M., Gibson, R.J., Sonis, S.T., and
Keefe, D.M.K., (2008). Serum levels of NF- B and pro-inflammatory cytokines
following administration of mucotoxic drugs, Cancer Biology and Therapy (in
press).
2. Logan, R.M., Bowen, J.M., Stringer, A.M., Gibson, R.J., Sonis, S.T., and
Keefe, D.M.K., (2008). Is the pathobiology of chemotherapy-induced alimentary
tract mucositis influenced by the type of mucotoxic drug administered? Cancer
Chemotherapy and Pharmacology (in press)
3. Logan RM, Gibson RJ, Bowen JM, Stringer AM, Sonis ST, Keefe DM. Characterisation
of mucosal changes in the alimentary tract following administration of irinotecan:
implications for the pathobiology of mucositis. Cancer Chemother Pharmacol.
2007 Aug 17 (in press).
4. Gibson, R.J., Cummins, A.G., Bowen, J.M., Logan, R.M., Healey, T and Keefe,
D.M.K., (2006). Apoptosis occurs early in the basal layer of the oral mucosa
following cancer chemotherapy, Asia-Pacific Journal of Clinical Oncology,
2(1): 39-49.
Collaborators:
Rachel collaborates with Professor Dorothy Keefe and the Mucositis Research
Group at the Royal Adelaide Hospital, Dr Richard Logan from the Discipline of
Oral Pathology, Dr Adrian Cummins from The Queen Elizabeth Hospital and A/Prof
Bill Breed from the Discipline of Anatomical Sciences.
Recent Paper Publications
|
