Boussioutas Group

Gastrointestinal Translational Research Laboratory

Research Overview

The Gastrointestinal Translational Research Laboratory investigates the clinical, genomic and immunological facets of gastrointestinal cancers and their premalignant conditions.

The main goal of the lab is to translate these findings into diagnostics, therapeutics and biomarkers of early detection. In order to facilitate their work, the lab has established a tissue biobank consisting of tissue and blood samples as well as extensive clinical data this is part of the MAGIC (Molecular Analysis of Gastrointestinal Cancer) cohorts. This also includes the Screening, Surveillance and Prevention cohort that is collecting clinical data, tissue and blood for biomarker discovery in patients at high risk of developing cancers. Patient recruitment and sample collection is currently ongoing. Our research incorporates molecular biology, cell biology, genomics techniques and utilises animal models.

The group is part of the Department of Gastroenterology at Alfred Health and Monash University with links to collaborators at multiple internal (Monash University) and external groups including WEHI, ONJCRI, VCCC and Peter Mac.

Student Research Projects

Staff

Group Leader

Postdoctoral Research Fellow
- Dr Rita Busuttil
PhD Students
- Dr Douglas Tjandra
- Dr Steven Nicolaides
- Dr Maria Kristina Vanguardia (with Dept of Medicine)
- Dr Nicholas Hannah (with Department of Medicine, University of Melbourne)
BMedSci(Hons) Students
- Mr Matthew Solazzo
- Ms Svetlana Brillantes
Visiting Scientist
- Dr Shiki Fujino

Projects

We welcome expressions of Interest from honours, masters, PhD and medical students. Alternate projects may be available based on interests, please contact us for a chat!

Functional characterization of candidate genes involved in the progression of gastric cancer
Gastric cancer (GC) is the fourth most common cancer globally. It has defined premalignant stages and progresses through Intestinal Metaplasia (IM) in the majority of cases. GC is diagnosed at advanced stage resulting in poor prognosis. Part of this is due to a lack of means to identify and screen persons at risk of GC. Relatively little is known about the key genetic events leading to IM. Our laboratory is currently in the process of completing the first comprehensive molecular and immunological analysis of IM in the world and we have identified a number of candidate genes which are likely to be involved in the progression of IM to GC. These could potentially be used to reliably predict the progression to GC in humans enabling clinical stratification of individuals into high-risk groups. We have access to a unique cohort of patient specimens with comprehensive clinical data. In addition, we have developed novel animal model systems and in vitro tools which we use to answer our research questions. This project would involve interrogation of clinical data and functional validation of these candidates using cell culture, organoid and potentially animal model systems. We are looking for motivated students (Honours, Masters and PhD students) to strengthen our group. The project will use broad range techniques including bioinformatics, cell culture, animal models and molecular biology.
Gastric cancer (GC) is the fourth most common cancer globally and 7th in incidence in Australia. It has a poor survival rate which can be attributed to the advanced stage at diagnosis in most patients. The molecular and cellular mechanisms underlying the development of GC are not well described. Traditionally cancer research involved studying the cancer cell itself. More recently, there has been growing interest in studying the normal cells and molecules which surround the cancer cell. This tumor microenvironment consists of a variety of stromal cell types including cells such as fibroblasts. It is believed that the dynamic communication between tumor cells and the surrounding cell types may play a major role in cancer initiation, progression and establishment of metastatic disease. The aim of this project is to investigate tumor-stromal interactions in gastric cancer utilizing established and primary cell lines. Once the molecular pathways by which a tumor cell progresses have been elucidated it is possible that these processes could be exploited in the development of novel therapeutics. Our previous genomic experiments have provided a number of exciting candidate genes that may be involved in this interaction. This is novel research that may have a major benefit to our understanding of cancer and improve patient outcomes. We have access to a unique cohort of patient specimens with comprehensive clinical data. In addition, we have developed novel animal model systems and in vitro tools which we use to answer our research questions. This project will use a broad range of techniques such as live cell microscopy, cell culture techniques (including organoids) and molecular biology to interrogate the function of gene products that influence tumour-stroma communication. This project may also involve the use of animal models.
Gastric cancer is associated with poor patient outcome due to advanced stage at diagnosis and lack of treatment options. Most deaths from GC occur as a result of recurrence of disease following surgery and/or treatment. We have recently identified SFRP4 (secreted frizzled related protein 4) as a gene which is highly expressed in GC and is involved in the invasion and ultimately recurrence of gastric cancer. We hypothesise that inhibition of SFRP4 will reduce the invasive capacity of the cancer resulting in better patient outcome. This project will test the efficacy of a novel neutralizing antibody targeting SFRP4 using in vitro and potentially in vivo model systems. This project would involve cell culture, molecular biology and, potentially, animal model systems.

Selected publications

Gastric Intestinal Metaplasia: Challenges and the Opportunity for Precision Prevention. DOI: 10.3390/cancers15153913.
CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia DOI: 10.1186/s12876-022-02268-zThe Role of Innate Immune Cells in Tumor Invasion and Metastasis DOI: 10.3390/cancers13235885
SFRP4 drives invasion in gastric cancer and is an early predictor of recurrence. DOI: 10.1007/s10120-020-01143-8
High-dimensional analyses reveal a distinct role of T-cell subsets in the immune microenvironment of gastric cancer. DOI: 10.1002/cti2.1127
Macrophage spatial heterogeneity in gastric cancer defined by multiplex immunohistochemistry. DOI: 10.1038/s41467-019-11788-4

Department of Cancer Medicine

Medicine, Nursing and Health Sciences