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Degli-Esposti Lab research

Collaborations | Student research projectsPublications

About Professor Degli-Esposti

Professor Degli-Esposti is an immunologist with an interest in understanding the mechanisms that regulate complex immune responses, and with recognised expertise in viral infection, autoimmunity, and immune-regulation. Her research has made significant contributions to understanding the immunological pathways invoked in response to viral infection (published in Nature Immunology, Immunity), the pathophysiology of the resulting disease (published in Blood, Immunity), and the strategies needed to improve clinical outcomes (published in Science, Lancet, Immunity, J Exp Med).


Our research

Research activities

If you want to contribute to new discoveries that will change lives, and wish to work with us, partner with us, or donate to support our research, please contact Professor Degli-Esposti.

Immunity is of central importance to all organisms, as their very survival is dependent upon the ability to fight infection
and disease. Professor Mariapia Degli-Esposti and Associate Professor Kim Jacobson are understanding how our immune
system identifies foreign invaders such as viruses and are paving the way in the development
of breakthrough treatments.

Current projects

  1. Understand the immune requirements for controlling chronic viral infection
  2. Define the role of viral infection in the aetiology of autoimmune and inflammatory diseases and their complications
  3. Improve the outcome of cytomegalovirus infection following bone marrow transplantation

Visit Professor Degli-Esposti's Monash research profile to see a full listing of current projects.

Our research involves the analysis of immune responses, principally in vivo, with the overall aim of determining how these responses are generated and maintained so that they can be harnessed therapeutically.

Our major research interests are:

  • Chronic viral infections
  • Transplantation
  • Autoimmunity and inflammation
  • Immunotherapy

Examples of our research focus areas include:

1. Defining the effect of bone marrow transplantation and graft versus host disease on the immunological control of Cytomegalovirus (CMV) using novel transplantation models.  

The major limitations of bone marrow transplantation (BMT) are graft versus host disease (GVHD) and opportunistic infections, which together result in the death of 20-30% of patients undergoing bone marrow transplantation (BMT). CMV represents the most predictable and problematical infection after BMT, with approximately 70% of patients experiencing viral reactivation and viral-induced disease. The cellular networks controlling this virus after transplantation are poorly understood. In addition, in the presence of GVHD, the ability to control CMV infection is dramatically inhibited, and we have recently clarified some of the relevant mechanisms (Blood 2015; Blood 2017; Science 2019). We are using our unique mouse models to determine how anti-viral immune responses can be harnessed to improve the control CMV infection in transplant recipients.

Mariapia-Image2

A pre-clinical model of CMV reactivation after bone marrow transplantation showing the model set-up, the detection of reactivated virus in the plasma, and the protective role of antibodies

2. Study the impact of MCMV infection on autoimmune disease aetiology, using a Sjogren’s Syndrome-like model.

Sjogren’s Syndrome is one the most prevalent autoimmune disorders where the body’s immune system attacks moisture producing glands. The resulting damage to the glands causes a severe decrease in the production of saliva and tears. The hallmark symptoms of Sjogren’s Syndrome are extremely dry eyes (which severely affects quality of life and can lead to corneal damage), and an inability to produce saliva (leading to problems with oral health and food digestion). Evidence from human studies suggests that infections may trigger or aggravate autoimmune diseases, but animal models to investigate the link between viral infection and autoimmune disease have been limited.

Using the MCMV infection model, we have been able to faithfully replicate a Sjogren’s Syndrome-like condition, where the clinical symptoms and organ pathology are very similar to the human disease (Immunity 2014). We are utilizing this model to elucidate the immune pathways that can be targeted to improve treatments for this common and debilitating human condition.

Histopathological (lymphocytic infiltrate) and functional (loss of saliva production) features of our pre-clinical Sjogren's Syndrome-like model

TRAIL+ NK cells control CD4+ T cells that damage the salivary glands leading to loss of exocrine function

2019 UNSW Eureka Prize for Scientific Research winner Professor Mariapia Degli-Esposti explaining the ground-breaking discovery she and her team made into cytomegalovirus.

Techniques/expertise

We utilise a combination of unique viral reagents (including recombinant viruses lacking specific viral genes or carrying specific epitopes or other molecules) and mouse systems (including gene-deficient and transgenic mouse models) together with state of the art molecular and cellular technologies to examine immune responses, viral replication, pathogenesis and disease.

  • In vivo virus infection
  • Viral engineering (BAC-based mutagenesis of MCMV genome)
  • Molecular biology
  • Tissue culture
  • Cellular immunology
  • High-parameter flow cytometry

Disease models

  • In vivo model of human cytomegalovirus (HCMV) infection
  • Transplantation models
  • In vivo models of autoimmunity
  • In vivo models of chronic inflammation

Collaborations

We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).

  • Professor Geoff Hill, Fred Hutchinson Cancer Research Center, Seattle USA
  • Professor Joe Sun, Memorial Sloan Kettering Cancer Center, New York, USA
  • Professor John Forrester, University of Aberdeen, Aberdeen, Scotland
  • Professor Ian Constable, Lions Eye Institute, Perth, Western Australia
  • Professor Elizabeth Rakoczy, Lions Eye Institute

STUDENT RESEARCH PROJECTS

The Degli-Esposti Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short-term research opportunities available. You are encouraged to contact Professor Mariapia Degli-Esposti regarding potential projects that align with the presented research themes.

MCMV, Immunity and Ageing (Honours project)

With average life spans increasing we face novel challenges in managing age-associated health decline. A key factor in maintaining overall health is a well-functioning immune system. How immunological challenges such as viral infections impact and shape the aging immune system is not well understood. In this regard, we are particularly interested in cytomegalovirus (CMV), a virus that is never fully cleared and remains with its host life-long. The ultimate aim is to gain a better understanding of how CMV infection shapes the immune system over time and how this affects the aging immune system.

Viral Infection and Autoimmunity (Honours project)

Viral infections have long been suspected to play a role in autoimmunity, with members of the herpes virus family such as cytomegalovirus (CMV) specifically implicated. We use the model of murine CMV, a natural pathogen of the mouse with high similarity to its human counterpart, to investigate the mechanisms underlying the generation of protective antiviral responses and how these correlate with the onset of autoreactive responses.  The goal of this project is to further extend our understanding of the processes and mechanisms underlying the generation of autoreactive immune populations in the context of viral infection.