Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group

Our vision is to accelerate an Extracellular Vesicle research program on the utility of blood-based biomarkers to benefit obstetrics and gynaecological cancer patients, clinicians, and healthcare providers.

About

The Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, led by Professor Carlos Salomon, focuses on research regarding extracellular vesicles (EVs) – small secretions from a wide range of cells, including placental and cancer cells. The lab has been studying EVs and their role within the production of new living organisms, such as pregnancy and cancer.

The past decade has observed an extraordinary explosion of research in the field of EVs. As the content of EV is cell-type specific, it is believed that it is a 'fingerprint' of the cell and its metabolic status.

The lab explores the idea that the EVs and their specific EV content (e.g. miRNAs and proteins) represent a precious biomedical tool, and may be used as biomarkers for the diagnosis and prognosis of a wide range of diseases including complication of pregnancies and malignant tumors.

EVs may engage in paracellular interactions (local cell-to-cell communication between the cells) and/or distal interactions (involving the release of EVs into biological fluids and transported to a remote site of action). The mechanisms involved in these phenomenon remain unclear, but the aim of the Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, is to analyse the role of EVs in the production of placental cells and tumor cells.

Quality management system

Professor Salomon contributed to establishing a Quality Management System (QMS) within the Centre for Clinical Diagnostics (CCD), University of Queensland (UQ). He had a leadership role in implementing an ISO17025 QMS and securing NATA accreditation. Within the Centre, I established the formed Exosome Biology Laboratory, and now the Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group to evaluate the clinical utility of extracellular vesicles as liquid biopsies, IVDs, and therapeutics. Much of his effort in this field has involved optimising isolation methods for extracellular vesicles and their analytical analysis – including the use of protein solution array (e.g., Luminex), mass spectrometry profiling (using MS/MS SWATH), and more recently miRNA analysis. Implementation of QMS in an academic environment ensures alignment of all activities with regulatory requirements for the development and delivery of medical devices to market. His UQ-based team has pioneered the development of EV genomic and protein biomarkers of disease that provide new opportunities to increase diagnostic performance – work conducted within UQCCR’s NATA-accredited facility that is compliant with international standards for the development and implementation of IVDs.

The ovarian cancer early detection alliance

One of the most significant contributions of my research program in the last 2 years has been the development of a test of early detection of ovarian cancer, OCRF-7, that displayed a classification efficiency of 98%. Based on these data, we successfully secured funding from two Medical Research Future Funding (MRFF) initiatives for a total of $4 million, and in both applications, the Ovarian Cancer Research Foundation (OCRF) is the partner organisation.

While the commercial pathway for developing a fit-for-purpose earlier detection test for ovarian cancer has proven to be extremely challenging, what is incontrovertible is that a global, collaborative (i.e, Prof. Usha Menon from The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)), and multidisciplinary approach will be required to develop and deliver such a test. To achieve this goal, Associate Professor Salomon has built a strategic alliance with the OCRF, LMRF, government (MRFF, NHMRC), industry, and national and international clinical key opinion leaders (KOLs) to:

Access a large cohort of prospectively collected appropriately-curated clinical samples;
Novel technological approaches to identify biomarkers of early-stage ovarian cancer;
A translational research facility compliant with regulatory-agency standards for the development of in vitro diagnostics (IVDs);
Advanced data mining and modelling expertise to develop robust multi-biomarker algorithms to deliver greater diagnostic accuracy;
Engagement of KOLs in the development and implementation of a new test;
Community educators and advocates; and
Commercialisation and distribution partners.

Moreover, a commercial partnership with ASX-listed company INOVIQ Ltd is providing access to novel technology platforms for EV biomarker discovery and future marketing and distribution opportunities.

The Ovarian Cancer Early Detection Alliance seeks to deliver the analytical and clinical performance data required by the TGA (and FDA) to advance the OCFR-7 test in a clinically feasible pathway to implementation to increase the survival rate of over 2000 women diagnosed with ovarian cancer in Australia annually. In collaboration with UniQuest and INOVIQ LTDA, when commercially available, the test will be distributed to major markets worldwide including USA, Europe, and Asia.

Media

Lion Medical Research Foundation
Ovarian Cancer Research Foundation
PerkinElmer, Inc.
INOVIQ Ltd
The Donald and Joan Wilson Foundation

Collaborators

Australia

Professor David McIntyre, The University of Queensland, Brisbane.
Professor David Simmnons, Western Sydney University, Sydney.
A/Professor Martha Lappas, University of Melbourne, Melbourne.
Professor Jon Hyett, The University of Sydney.
A/Professor Amirali Popat - The University of Queensland
Professor Jusuke Yamauchi - The University of Queensland
Professor Andreas Obermair - The University of Queensland
Professor Monika Janda - The University of Queensland
A/Professor Joy Wolfram - The University of Queensland
Professor Amanda Barnard - Australian National University
Dr Emanuel Pelosi - The University of Queensland
A/Professor Muhammad Shiddiky – Griffith University
Professor Gregory Rice - The University of Queensland

International

Professor Ramkumar Menon, University of Texas Medical Branch, Galveston, USA.
Professor Thomas Jansson, University of Colorado, Denver, USA.
Professor Teresa Powell, University of Colorado, Denver, USA.
Dr. Sherri Longo, Ochsner Medical Center, New Orleans, USA.
Dr. Li Li, Ochsner Medical Center, New Orleans, USA.
Dr. Richard Kline, Ochsner Medical Center, New Orleans, USA.
Professor Luis Sobrevia, Pontifical Catholic of Chile, Santiago, Chile.
Professor Andreas Molller, The Chinese University of Hong Kong
Professor William Lowe - Northwestern University
Professor Usha Menon – University College London
A/Prof Mahesh Choolani – National University of Singapore
Professor Matthew Wood – Oxford University
Professor Fidelma Dunne – University of Galway

Group Leader

Professor Carlos Salomon Gallo

Theme Leaders

Dr Andrew Lai

Proteomics Theme Leader

Dr Dominic Guanzon

Genomics Theme Leader

Dr Soumyalekshmi Nair

Therapeutics Theme Leader

Support staff

Dr Priyakshi Kalita de Croft
Miss Katherin Scholz Romero
Miss Lily Kessling

Students

Shikha Rani
Nihar Godbole
Angel Nilesh D’Crus
Aayushi Ghodasara
Azad Hossain
Pragati Lodha
Pranav Girish Banvi
Anas Emerizal

We have multiple projects available for students associated with Obstetrics and Gynae-Oncology.

Obstetrics

The foundations of health throughout life are laid down during fetal development. Complications of pregnancy that compromise fetal development have profound effects not only on the immediate outcomes of pregnancy but also on the life-long disease risk susceptibility of the offspring. Around 300,000 babies are born in Australia each year. The growth and development of more than 45,000 of these babies is compromised by complications of pregnancy. Complications of pregnancy, such as: pregnancy-induced maternal high-blood pressure (preeclampsia, PE); pregnancy-induced diabetes (gestational diabetes mellitus, GDM); small for gestational age (intrauterine growth restriction, IUGR), stillbirth and preterm birth (delivery before 32 completed weeks of pregnancy, PTB) result in significant adverse health outcomes for the newborn; an increased short term risk of mortality and morbidity and an increased life time risk of metabolic and cardiovascular disease. In most cases, poor pregnancy outcome is not anticipated or diagnosed early enough to significantly change health outcomes. Currently available tests are either not of sufficient accuracy for screening the general obstetric population or lack sufficient evidence-based data to define clinical utility and justify implementation into standard practice. We have strong biomarker and therapeutic program focussed on extracellular vesicles for a wide range of complication of pregnancies.

Gynaecological cancers – Ovarian cancer

Ovarian cancer (OC) is one of the most diagnosed gynecological cancers in women. Due to the lack of effective early stage screening, women are more often diagnosed at an advanced stage; therefore, it is associated with poor patient outcomes. There are a lack of tools to identify patients at the highest risk of developing this cancer. Moreover, early detection strategies, therapeutic approaches, and real-time monitoring of responses to treatment to improve survival and quality of life are also inadequate. Tumor development and progression are dependent upon cell-to-cell communication, allowing cancer cells to re-program cells not only within the surrounding tumor microenvironment, but also at distant sites. Recent studies established that extracellular vesicles (EVs) mediate bi-directional communication between normal and cancerous cells. EVs are highly stable membrane vesicles that are released from a wide range of cells, including healthy and cancer cells. They contain tissue-specific signaling molecules (e.g., proteins and miRNA) and, once released, regulate target cell phenotypes, inducing a pro-tumorigenic and immunosuppressive phenotype to contribute to tumor growth and metastasis as well as proximal and distal cell function. Thus, EVs are a "fingerprint" of their cell of origin and reflect the metabolic status. Additionally, via the capacity to evade the immune system and remain stable over long periods in circulation, EVs can be potent therapeutic agents.