Dr Sara Chiaretti

Postdoctoral Research Fellow

The University of Queensland Diamantina Institute
Faculty of Medicine
s.chiaretti@uq.edu.au
+61 7 344 36921

Overview

Shortly after graduating in Medical Biotechnology with a thesis project in cell biology, I started my research career at the Diabetes Research Institute at the San Raffaele Scienific Institute (Milan, Italy) where I participated in a project investigating the relevance of in vivo non-invasive magnetic resonance imaging (MRI) for the detection of intrahepatic transplanted pancreatic islets.

In 2009 I had the opportunity to join an important Italian Pharma (Nerviano Medical Sciences, NMS, s.r.l, Milan, Italy) whose aim was the development of new kinases inhibitors as anti-cancer therapeutics. I worked within their Department of Cellular Biology investigating and validating mechanisms of action and anti-tumor efficacy of new kinase inhibitors both in vitro and in vivo.

In November 2011 I was awarded a three-year scholarship to enter the Ph.D. program in Experimental Medicine and Oncology at University of Insubria (Varese, Italy), under the supervision of Prof Ivan De Curtis at the San Raffaele Scientific Institute (Milan, Italy). During my Ph.D. I studied both in vitro and in vivo the molecular mechanisms that lead tumor cell migration and invasion. I focused on breast cancer using the invasive human triple negative breast cancer model MDA-MB-231.

In 2016, in order to study in depth the tumor microenvironment, I joined Dr Mazzieri laboratory in Brisbane where I am currently a postdoctoral research fellow. The projects I am involved in aim to combine innovative immunotherapies to reverse the immunosuppressive tumor microenvironment and improve the outcome of breast cancer therapies.

Research Interests

  • New strategies to reverse the immunosuppressive tumor microenvironment
    The establishment of an immunosuppressive tumour microenvironment is one of the fundamental hallmarks of cancer and the major impediment to the successful application of anti-tumour immunotherapy. In order to reverse the immunosuppressive tumor microenvironment, the first project of our laboratory aims to modulate two important aspects of the tumour microenvironment: tumour angiogenesis and immunosuppression. Our laboratory takes advantage of a specific subpopulation of pro-tumoural macrophages: the TIE2-expressing monocytes/macrophages (TEMs) endowed with pro-angiogeic and immunosuppressive activities. It has been recently demonstrated that targeting the ANG2/TIE2 pathway inhibits tumour angiogenesis, growth, and metastasis. ANG2 also modulates the immunosuppressive activity of TEMs. With the final goal of developing new and more effective antitumour and anti-metastasis therapies, we are investigating whether the blockade of ANG2 results in a less permissive and less immunosuppressive tumour microenvironment able to enhance the efficacy of established cancer immunotherapies. As second strategy to reverse the immunosuppressive microenvironment, our laboratory turned a pro-tumoural population of macrophages, the TIE2 expressing monocyte/macrophages (TEMs), into cellular vehicles for the tumour targeted delivery of IFN-alpha. This was achieved by exploiting TIE2 monocytes-tumour homing capability and selective expression of the angiopoietin TIE2 receptor. This cell- and gene-based delivery therapy strongly inhibits primary breast cancer tumours and breast cancer lung metastasis in mouse and human hematochimeric models. Aim of this project is to combine the multiple activities of type I IFNs with checkpoint modulators molecules to promote and improve the outcome of cancer immunotherapy

Research Impacts

Breast cancer was the most common diagnosed cancer among women in 2013 in Australia and the second cancer-related death causes in 2014. This has a big impact on Australian women life because it has been estimated that in 2017 1 in 41 women has the risk of dying of breast cancer by their 85th birthday. Breast cancer has therefore a high significant social and economical impact. For these reasons, new strategies for therapeutic intervention are highly in need. In order to improve immunotherapy outcome in breast cancer patients, the project I am working on aim at overcoming tumour immune evasion and at enhancing the ability of the immune system to fight the tumour. My findings will provide preclinical data supporting the feasibility and efficacy of new combination therapies for the treatment of advanced and metastatic breast cancer including triple negative breast cancer, that has nowadays limited therapeutic options and poor outcome.

Qualifications

  • PhD in Experimental Medicine and Oncology, Insubria.

Publications

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Publications

Journal Article