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).

The Gut Microbiome Group

The Gut Microbiome Group is a recently established dynamic and innovative research laboratory in the School of Medical Sciences (Level 3, Medical School North) headed by Dr Rachel Gibson. As a branch of the internationally recognised Mucositis Research Group, the focus of their research is to investigate the toxic effects of chemotherapy on the gut microbiome (bacterial population) of cancer patients and the development of clinically diagnosed diarrhoea (a manifestation of intestinal mucositis).  Specific changes in the gut microbiome may lead to the development of a biomarker to predict the onset of the toxic effects of chemotherapy and improve patient care.  This novel research may also lead to the development of intervention agents to prevent or treat chemotherapy-induced mucositis and diarrhoea. The group members have extensive experience in a variety of techniques and are widely published in fields including, pathology, molecular biology, microbiology and immunology. Their studies are supported by access to the research laboratories first-class facilities and a stimulating work environment.

Group Members:

Laboratory Head: Dr Rachel Gibson
Visiting Research Fellow: Dr Andrea Stringer
Research Assistant: Ms Bronwen Mayo
Honours candidate: Mr Daniel Thorpe

Possible Honours/PhD Projects

1. Development of an animal model to study novel targeted therapies for cancer

Supervisors: Dr Rachel Gibson, and Dr Joanne Bowen.

Cancer treatment causes significant injury to normal "mucosal" tissues and is a major cause of morbidity in patients. Recently, a new class of therapy, known as “targeted therapy”, has been introduced into the clinical setting to treat cancers, with spectacular success. However, these targeted therapies can also cause significant damage to normal tissues. This damage is referred to as “mucosal injury” rather than “mucositis” as it is not caused by chemotherapy or radiotherapy, rather it is caused by a specific targeted small molecule.  Currently there is no established animal model available to investigate the mechanisms by which these small molecules induce mucosal injury. Therefore the aim of this study is to develop an appropriate animal model.  An accurate animal model will prove invaluable for the development of preventative treatments of targeted therapy-induced mucosal injury. Testing compounds in a clinically relevant animal model will streamline translation from bench to bedside.  This project will use the Wistar rat as the study animal as this species has an appropriate metabolic profile to study small molecules and previous pre-clinical work has been conducted in this species. Furthermore a tumour, known as Walker 256, spontaneously arose in this species, making it ideal to study.  Students will be exposed to a wide range of techniques including: small animal handling (including minor procedures), histological and histopathological techniques, immunohistochemistry and microdissection.

2. Chemotherapy-induced diarrhoea: role of the gut microbiome

The Human Microbiome Project (HMP) has been recently established and is identifying novel methods of thinking about the role of the human microbiome in determining predisposition to a range of pathologies (Turnbaugh, 2007 Nature 449:804) including chemotherapy-induced diarrhoea (CID).  Furthermore the HMP is defining parameters which are fundamental to develop strategies to manipulate the microbiome (Turnbaugh, 2007 Nature 449:804).  With this in mind, this study has been designed to firmly establish that the human gut microbiome plays a key role in the development of CID.  Our previous published studies have clearly demonstrated that bacterial changes occur prior to the onset of diarrhoea (Stringer et al, 2008, Cancer Biol Ther; Stringer et al, 2009 Int J Exp Path). The aim of this proposal is to conduct a larger time course study in the clinic to further measure the changes to the gastrointestinal microbiome and correlate these with circulating pro-inflammatory cytokine changes.  Results from this study will impact clinical practice by identifying clinically relevant biomarkers allowing for early intervention and management of patients with chemotherapy-induced diarrhoea.  This study will examine the gastrointestinal microbiome using both qualitative microbiology and quantitative real time PCR in patients receiving chemotherapy, which our group has established and validated the protocols.  Changes in faecal flora will be investigated using our established methods and correlated with circulating pro-inflammatory cytokine expression.  This shall determine how these changes relate specifically to the diarrhoea observed following chemotherapy and will allow the determination of specific clinically relevant biomarkers for the development of chemotherapy-induced diarrhoea.  Students will be exposed to a wide range of techniques including: clinical patient recruitment, routine microbiological techniques, ELISA’s, RT-PCR, immunohistochemistry, and histopathology.

3. Cytokines and chemotherapy-induced diarrhoea

In recent years it has been realised that various cytokines play important roles in the pathogenesis of mucositis.  Previous studies have demonstrated that cytokines that target epithelial cell proliferation such as epidermal growth factor (EGF) (Sonis et al., 1992 Oral Surg, Oral Med Oral Path, 74: 749) or transforming growth factor-beta 3 (TGF-β3) (Sonis, 1997, Oral Oncol 33:47) modified the course of mucositis in animal models.  More recently, studies in our laboratory have clearly demonstrated that the transcription factor NF-kB is upregulated in the mucosa following chemotherapy (Logan 2008 Cancer Biol Ther).  NF-kB results in the upregulation of pro-inflammatory cytokines (TNF, IL-1B and IL-6), which play an important role in the pathogenesis of mucositis (Logan 2008 Cancer Biol Ther).  Much of the information regarding chemotherapy-induced diarrhoea in the published literature is based on clinical observations with very little basic science.  Recent research conducted in our laboratory has attempted to correct this anomaly and has found a correlation between chemotherapy-induced diarrhoea and an altered gastrointestinal microbiome (Stringer et al, 2008, Cancer Biol Ther; Stringer et al, 2009 Int J Exp Path).  In addition research has shown that circulating pro-inflammatory cytokines play a key role in the development of mucositis However, the role that anti-inflammatory cytokines play has not been determined.  This project aims to determine if the levels of anti-inflammatory cytokines alter in response to chemotherapy.  Students will be exposed to a wide range of techniques including ELISAs, RT-PCR, and immunohistochemistry.

Relevant Publications

1. Gibson RJ. (2009).  Gut microbiome and intestinal mucositis: a new challenge for researchers Cancer Biology and Therapy (invited commentary – in press accepted 21 January 2009) IF 2.873
2. Gibson RJ, and Stringer AM. (2009). Chemotherapy-induced diarrhoea.  Current Opinion in Palliative and Supportive Care (invited review – in press accepted 7 December 2008)
3. Stringer AM, Gibson RJ, Logan RM, Bowen JM, Yeoh ASJ and Keefe DMK (2009).   Gastrointestinal microflora and mucins play a role in the development of 5-Fluorouracil-induced gastrointestinal mucositis in rats. Experimental Biology and Medicine (in press - accepted 18 January 2009) IF 2.845
4. Stringer AM, Gibson RJ, Bowen JM, and Keefe DMK,  (2009).  Chemotherapy-induced changes to microflora: Evidence and implications of change.  Current Drug Metabolism 10(1):79-83.  IF 4.490
5. Stringer AM, Gibson RJ, Logan RM, Bowen JM, Laurence J, and Keefe DMK.  (2009).  Irinotecan-induced mucositis is associated with changes in intestinal mucins. Cancer Chemotherapy and Pharmacology (epub ahead of print). IF 2.568
6. Logan RM, Bowen JM, Stringer AM, Gibson RJ, Sonis ST, and Keefe DMK,  (2009).  Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered? Cancer Chemotherapy and Pharmacology 63(2):239-51 IF 2.873
7. Stringer AM, Gibson RJ, Bowen JM, Logan RM, Ashton K, Yeoh ASJ, Al-Dasooqi N and Keefe D (2009).  Irinotecan-induced mucositis manifesting as diarrhoea corresponds with an amended intestinal flora and mucin profile. International Journal of Experimental Pathology (in press – accepted 9 January 2009) IF 2.460

 

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