Projects per year
Personal profile
Biography
The common factor in all disease
Dr Ashley Mansell views inflammation as the basis of nearly all disease, including cancer, heart disease and diabetes. Inflammation provides the body's first line of defence against disease. Recent discoveries show it is also critical in signalling the body to mount more sophisticated and long-term defences.
When this signalling goes wrong, disease follows.
Ashley studies the immune system and its most fundamental disease-fighting process - how the body first detects it is injured or under attack from microbes.
Despite decades of research, this mechanism was misunderstood until the discovery of a family of receptors - called the Toll-like receptors - that acts as the body's central alarm system. The receptors allow the body to mount a rapid response to disease in the form of inflammation. They also amount to a central mechanism that can determine the outcome of fights against many diseases.
Ashley was working with Professor Luke O'Neill in Dublin, Ireland, when the breakthrough happened. He was using his science degree 'to see the world' and the discovery launched him into a career in this important area of research, including a role with Monash University.
'Inflammation has a lot of firepower when it comes to fighting disease,' Ashley says. 'But it lacks subtlety or specificity. I jokingly call inflammatory responses the shock-and-awe arm of the immune system. It sees the problem and it just responds - a bit blindly and a bit violently - and in the process it causes collateral damage to the body.'
A typical example is the joint pain, headache and fever associated with fighting the influenza virus. But the problem can run deeper. Inflammation is known to overwhelm the body in a runaway reaction that results in auto-inflammatory disorders such as septic shock.
Even more critical is the growing evidence that more sophisticated immune responses, such as those needed to fight cancer, are initiated and guided by inflammation.
By studying inflammation, Ashley and other researchers in his field are shedding new light on why diseases such as cancer escape the immune system's efforts to control them. Inflammation is also a factor in more than 100 auto-immune diseases, including arthritis and asthma. These involve antibodies inappropriately attacking healthy tissue.
For these reasons, Ashley focuses on the genes that control the inflammatory response. Called pattern recognition receptors, they have stirred international interest from laboratories seeking better treatment for patients with specific diseases.
'Globally, we have realised that inflammation is probably the basis of nearly all disease. Cancer, heart disease and obesity included. That means inflammation is an emerging field with the potential to clinically redefine disease.'
Ashley is working in collaboration with a German heart disease laboratory that has detected cholesterol micro-crystals in blocked arteries. The crystals are suspected of triggering disease as they are proving to be potent inducers of self-harming forms of inflammation. Other collaborations see him assisting laboratories working on influenza virus, hepatitis B and asthma.
Internationally, the research is changing how pharmaceutical companies think about disease. Opportunities are being created to develop a new class of therapies and drugs. Such a prospect fascinates Ashley. 'I like to think my research can make a difference, that it can benefit humanity,' he says. 'I may ultimately provide just a small part of a solution. But the idea that I can contribute at all is very motivational.'
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Education/Academic qualification
Biochemistry, PhD, Bacterial Products as Activators of NF-kappaB, Trinity College Dublin
Award Date: 31 Oct 2001
Chemistry, BSc, MONASH UNIVERSITY
Award Date: 18 Nov 1988
Research area keywords
- Host-Pathogen Interactions
- Infectious Disease
- Immunology
- Molecular Biology
- Biochemistry
- Biomedicine
- Inflammation
- Underlying Basis of Disease
- Innate Immunity
- Regulation of Immune Responses
- Pattern Recognition Receptors
- Immunometabolism
Collaborations and top research areas from the last five years
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Targeting pyroptosis to limit the severity of influenza virus infections
Tate, M. (Primary Chief Investigator (PCI)), Lawlor, K. (Associate Investigator (AI)), Mansell, A. (Associate Investigator (AI)) & Hertzog, P. (Associate Investigator (AI))
1/01/23 → 31/12/26
Project: Research
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Potential of the NLRP3 inflammasome as a biomarker and therapeutic target in silicosis
Tate, M. (Primary Chief Investigator (PCI)) & Mansell, A. (Chief Investigator (CI))
Department of Health and Aged Care (Australia)
1/08/21 → 31/07/24
Project: Research
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Finding the balance – Reducing inflammation during severe influenza infections
Tate, M. (Primary Chief Investigator (PCI)) & Mansell, A. (Chief Investigator (CI))
National Health and Medical Research Council (NHMRC) (Australia)
1/01/20 → 31/12/22
Project: Research
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Targeting the inflammasome; the key to curing Cerebral Palsy?
McDonald, C. (Primary Chief Investigator (PCI)), Dowling, J. (Chief Investigator (CI)), Miller, S. (Chief Investigator (CI)), Mansell, A. (Chief Investigator (CI)), Fahey, M. (Chief Investigator (CI)) & Hodges, R. (Chief Investigator (CI))
1/03/18 → 28/02/20
Project: Research
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INFLAMMASOMES AND INTERLEUKIN-18 SIGNALLING: NOVEL BIOMARKERS AND THERAPEUTIC TARGETS FOR KIDNEY DISEASE
Drummond, G. (Primary Chief Investigator (PCI)), Hickey, M. (Chief Investigator (CI)), Mansell, A. (Chief Investigator (CI)), Sobey, C. G. (Chief Investigator (CI)) & Vinh, A. (Chief Investigator (CI))
1/01/18 → 31/12/21
Project: Research
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Aggregated Hendra virus C-protein activates the NLRP3 inflammasome to induce inflammation
Barry, K., Harpur, C., Lam, M., Tate, M. D. & Mansell, A., 10 Nov 2023, In: Journal of Inflammation. 20, 1, 12 p., 38.Research output: Contribution to journal › Article › Research › peer-review
Open Access3 Citations (Scopus) -
A novel dual NLRP1 and NLRP3 inflammasome inhibitor for the treatment of inflammatory diseases
Docherty, C. A. H., Fernando, A. J., Rosli, S., Lam, M., Dolle, R. E., Navia, M. A., Farquhar, R., La France, D., Tate, M. D., Murphy, C. K., Rossi, A. G. & Mansell, A., 22 Jun 2023, In: Clinical & Translational Immunology. 12, 6, 18 p., e1455.Research output: Contribution to journal › Article › Research › peer-review
Open Access26 Citations (Scopus) -
Gasdermin D promotes hyperinflammation and immunopathology during severe influenza A virus infection
Rosli, S., Harpur, C. M., Lam, M., West, A. C., Hodges, C., Mansell, A., Lawlor, K. E. & Tate, M. D., 9 Nov 2023, In: Cell Death & Disease. 14, 11, 11 p., 727.Research output: Contribution to journal › Article › Research › peer-review
Open Access19 Citations (Scopus) -
IL11 activates the placental inflammasome to drive preeclampsia
Menkhorst, E., Santos, L. L., Zhou, W., Yang, G., Winship, A., Rainczuk, K. E., Nguyen, P., Zhang, J.-G., Moore, P., Williams, M., Cao, K. A. L., Mansell, A. & Dimitriadis, E., 2023, In: Frontiers in Immunology. 14, 16 p., 1175926.Research output: Contribution to journal › Article › Research › peer-review
Open Access4 Citations (Scopus) -
NLRP1- A CINDERELLA STORY: a perspective of recent advances in NLRP1 and the questions they raise
Barry, K., Murphy, C. & Mansell, A., Dec 2023, In: Communications Biology. 6, 1, 7 p., 1274.Research output: Contribution to journal › Short Survey › Other › peer-review
Open Access21 Citations (Scopus)