From the bedside to the bench and back: A translational career for Alex Boussioutas

Professor Alex Boussioutas is Central Clinical School's
recently appointed Head of Department of Gastroenterology

Professor and Director of Gastroenterology Alex Boussioutas holds a joint senior academic and clinical role with Alfred Health and Monash University, the latest of a string of prestigious appointments. He has also had a remarkable research career.

by Anne Crawford

Gastroenterologist Professor Alex Boussioutas began his research career driven by a fascination with the molecular aspects of disease. It was the ‘90s when the nexus of molecular biology and genomics was an escalating field. “I figured the only way I could find out about that properly was to do a PhD in it,” he said.

In 2000, while working as a recently credentialled gastroenterologist at St Vincent’s Hospital, Professor Boussioutas launched into a doctorate at the University of Melbourne on the molecular aspects of gastric cancer. In the same year he was appointed the gastroenterologist at Peter MacCallum Cancer Centre where he carried out this research.

 “The whole genome era was really beginning,” he said. “I was one of the early investigators at the forefront of the genomics of the time, which were rudimentary expression arrays back then.

“It was very new to Australia – and very new to the world.”

Stanford University was predominantly leading the field but Professor Boussioutas and other Australian researchers were in the mix.

“Mine was one of the first PhDs to actually publish in that space,” he said. “It was one of the landmark studies of the time, the first comprehensive analysis of gastric cancer in the world with the biggest cohort at the time.” 

Professor Boussioutas was awarded the Peter MacCallum Medal for scientific excellence in 2004 for his PhD. The paper, published in 2003 by ‘Cancer Research’, is still highly cited. That work led to a tenured senior lecturer position at the University of Melbourne. 

Professor Boussioutas then formed collaborations researching cancer within the gastric intestinal tract and genomics and became the only Australian collaborator on the US-based Cancer Genome Atlas Network in Upper GI Cancer, which published two landmark studies in ‘Nature’ characterising gastric and oesophageal cancer. That long-term study comprehensively characterised stomach cancer into four distinct genomic groupings.

“There are some fundamental things that have resulted out of that looking at different sub-groups of gastric cancer, as well as immunological aspects of gastric cancer, which got a lot of interest in the field of oncology,” he said. “We found two of the subtypes are very amenable to immunological treatment of gastric cancer (GC), which is one of the things that resulted from that.”

Other important papers followed. A study published in ‘Clinical & Translational Immunology’ in 2020 found the combination of CD8+ T cells and FOXP3+CD4+ T cells formed a significant prognostic marker for GC patients and could potentially be targeted and applied as a novel immune therapy. Research published in ‘Gastric Cancer’ in 2021, by first author Dr Rita Busuttil (now working at Monash with Professor Boussioutas), found that the protein-coding gene SFRP4 drives the invasion of gastric cancer and can be a predictor of recurrence.   

Almost two decades since his PhD, Professor Boussioutas has progressed some of his original research towards finding what he calls the ‘Holy Grail’ of preventive medicine: “Who is it best to screen for the prevention of cancer?”

The research, prompted by Professor Boussioutas’ interest in a pre-malignant condition in the stomach similar to Barrett’s Oesophagus, looks at intestinal metaplasia (IM) as a marker that a person might develop gastric cancer. 

Gastric cancer is the fifth most common and third most lethal cancer globally.

“The idea is to try to use the premalignant nature of these lesions as a marker of who to screen. If we screen everybody it’s expensive and a bit of a waste because only a small proportion of people will eventually progress to cancer.”

The findings of his most recent study suggest that the human antigen CD10 is an “outstanding biomarker” for what’s called complete intestinal metaplasia. CD10 in combination with the Das1 protein may be used as a biomarker for IM glands at greater risk of progression to gastric cancer. 

It concluded that the clinical use of these biomarkers is one step in the direction of improved patient stratification and targeted surveillance; the most at-risk people could be treated early and cured. “I call it precision prevention,” Professor Boussioutas said. “If you identify gastric cancer and treat it at an early stage you can actually have very good outcomes but most of our patients are diagnosed at a late stage when it’s progressed and has lymph involvement or mestastases outside the stomach, when the mortality rate is very high and prognosis poor.”

As he’s researched, Professor Boussioutas has held several impressive academic and clinical leadership roles.  

Among them he has been the Deputy and Acting Director of Gastroenterology at Western Health; Head of Gastroenterology PMCI; Deputy, and Acting Director of Gastroenterology at Royal Melbourne Hospital (RMH). He has been the longest-running Associate Dean for Graduate Research in the Faculty of Medicine, Dentistry and Health Sciences at the University of Melbourne, and an honorary Associate Professor in the School of Public Health, University of Sydney. 

In June 2021, Professor Boussioutas joined the Central Clinical School as Professor and Director of Gastroenterology, a joint senior academic and clinical leader with Alfred Health and Monash University. He also holds the additional role of Program Director for Medical Specialties Alfred Health. 

He said the research component of the Monash role appealed and the way the Central Clinical School is integrated with clinical aspects of research.  

“As Director of Gastroenterology there are a lot of opportunities to actually make research happen and that’s very attractive,” he said. “There’s a lot more of an understanding here at Monash that your clinical position actually influences your research and your teaching and is a testament to the success of this university approach.

“Monash has these unique roles; the professor/director roles are true partnerships between the university and the hospital.”

Professor Boussioutas said other exciting research being conducted at the CCS included: the ongoing FODMAP studies; clinical research into variants of Inflammatory Bowel Disease; research bridging the gap between gastric intestinal research and oncology; investigating the immunological complications that arise from highly effective immunotherapies such as immune checkpoint inhibitors; a clinic looking at novel therapies including faecal microbiota transplants; investigations into the functional gastrointestinal tract and the nexus of what happens between the brain, gut microbiome and interaction with aspects of psychology, psychiatry and nutrition.

Professor Boussioutas has exciting plans to create a “gastrointestinal precinct” at The Alfred complex. “Very translational, from bench to bedside and importantly, bedside back to bench,” he said.

It’s an interplay that has characterised his career.

See more

http://ccsmonash.blogspot.com/2021/04/welcome-to-alex-boussioutas-new.html

Koulis A, Di Costanzo N, Mitchell C, Lade S, Goode D, Busuttil RA, Boussioutas A. CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric intestinal metaplasia. BMC Gastroenterol. 2022 Apr 21;22(1):197. doi: 10.1186/s12876-022-02268-z. PMID: 35448971; PMCID: PMC9026694. https://pubmed.ncbi.nlm.nih.gov/35448971/

To read Professor Boussioutas’ previous papers:

Busuttil RA, George J, House CM, Lade S, Mitchell C, Di Costanzo NS, et al. SFRP4 drives invasion in gastric cancer and is an early predictor of recurrence. Gastric Cancer. 2021;24(3):589-601. https://www.ncbi.nlm.nih.gov/pubmed/33277667

Wang M, Huang YK, Kong JC, Sun Y, Tantalo DG, Yeang HXA, et al. High-dimensional analyses reveal a distinct role of T-cell subsets in the immune microenvironment of gastric cancer. Clin Transl Immunology. 2020;9(5):e1127. https://www.ncbi.nlm.nih.gov/pubmed/32377339

 Cancer Genome Atlas Research N, Analysis Working Group: Asan U, Agency BCC, Brigham, Women's H, Broad I, et al. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017;541(7636):169-75. https://www.ncbi.nlm.nih.gov/pubmed/28052061

 The Cancer Genome Atlas Research N, Analysis Working Group: Dana-Farber Cancer I, Institute for Systems B, University of Southern C, Memorial Sloan Kettering Cancer C, Agency BCC, et al. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014 Vol. 513 Issue 7517 Pages 202-9 https://www.ncbi.nlm.nih.gov/pubmed/25079317