Lisa Alleva is a Senior Research Officer in the School of Biochemistry and Molecular Biology at the ANU. In April 2008 she was awarded a grant from the NHMRC in their Special Call for Research Applications into Complementary and Alternative Medicine (CAM), for work that focuses on using CAM to modulate immunopathology during influenza.  Lisa carried out her PhD in BaMBi (1994-1998), working on the role of proinflammatory cytokines in coccidiosis, and during this time was funded by an Australian Postgraduate Award and a Junior Research Fellowship from the Rural Industries Research and Development Corporation.  In 1999 she joined Kiaran Kirk's laboratory, working on calcium regulation in the human malaria parasite and in vivo assessment of an antifungal agent with antiplasmodial activity.  In 2001 she moved to Ian Clark's lab, working on the mechanisms of disease in human malaria, with emphasis on the proinflammatory mediator HMGB1.  In 2006 Lisa's focus shifted from mechanisms to treatment, when she began working with murine influenza models and investigating drugs that lower proinflammatory cytokine levels and modulate the immune response.  This work was inspired by the writings of David Fedson.

Contact Details

E: Lisa.Alleva@anu.edu.au T: (+61 2) 6125 4940 F: (+61 2) 6125 0313

Main Research interests

• Minimising influenza disease using generic medications, and Complementary and Alternative Medicines (CAM). • The role of High Mobility Group Box 1 protein (HMGB1) in infectious diseases.

Current Research Group

from left: Ian Clark, Michael Li, Lisa Alleva, Megan Downie (at Boffins on the ANU campus) Alleva Lab Members Megan Downie - Post-doctoral fellow Michael Li - Honours student Simon Arnett - Medical school research project Sampada Sudarshan - Masters in Biotechnology research project

Research Activities

It is now accepted that inflammatory cytokines produced by the host in response to an invading pathogen initiate both host protection and pathology. This concept was begun by Ian Clark in the early 1980s. By viewing these cytokines as causing the observed disease, this logically leads to investigation of treatments that lower their levels and thus prevent or reduce the severity of the disease. Such treatments are novel because they target the host response rather than the pathogen itself. We recently demonstrated "proof of concept" when we showed that the drug gemfibrozil, used to lower lipid levels in humans, halved the mortality associated with severe influenza virus infections in mice. Gemfibrozil is known to reduce levels of pro-inflammatory cytokines via activation of the nuclear receptor PPAR-alpha.

Further Reading

Clark, IA et al. (1981). Possible importance of macrophage-derived mediators in acute malaria. Infection and Immunity, 32:1058. Clark, IA (2007). How TNF was recognized as a key mechanism of disease. Cytokine and Growth Factor Reviews, 18:335. Fedson, DS (2006). Pandemic influenza: a potential role for statins in treatment and prophylaxis. Clinical Infectious Diseases, 43:199.

Recent Publications

2009 Alleva LM, Cai C and Clark IA.  Using complementary and alternative medicines to target the host response during severe influenza (2009).  Evidence-based Complementary and Alternative Medicine (accepted 30.08.09). Clark IA, Alleva LM. Is human malarial coma caused, or merely deepened, by sequestration? Trends Parasitol. (2009) 25:314-318. Clark IA, Alleva LM. Invited commentary on David Fedson's article “Confronting the next influenza pandemic with anti-inflammatory and immuno-modulatory agents: why they are needed and how they might work” (2009). Influenza Other Respi. Viruses 3:199-201. 2008 Clark IA, Budd AC, Alleva LM.  Sickness behaviour pushed too far - the basis of the syndrome seen in severe protozoal, bacterial, and viral, diseases, and post-trauma (2008).  Malaria Journal 7:208. Alleva, LM1, Budd, AC1 and Clark, IA. Systemic release of high mobility group box 1 protein during severe murine influenza (2008). Journal of Immunology 181:1454-59. Clark, IA, Alleva, LM, Budd, AC and Cowden, WB. Understanding the role of inflammatory cytokines in malaria and related diseases (2008). Travel Medicine and Infectious Diseases 6:67-81. 2007 Alleva, LM (2007). Biologically active versus immunoreactive high-mobility group box 1. Critical Care Medicine 35:1809. Budd, AC1, Alleva, LM1, Alsharifi, M, Koskinen, A, Smythe, V, Müllbacher, A, Wood, J and Clark, IA (2007). Increased survival after gemfibrozil treatment of severe mouse influenza. Antimicrobial Agents and Chemotherapy 5:2965-2968. 2006 Clark, IA, Budd, AC, Alleva, LM, Cowden, WB (2006). Human malarial disease: a consequence of inflammatory cytokine release. Malaria Journal 5:85. Alleva, LM (2006). Taking time to savor the rewards of slow science. Nature: 443:271. Alleva, LM (2006). Comment on “Cutting Edge: Extracellular high mobility group box-1 protein is a proangiogenic cytokine.” The Journal of Immunology 176:4512. 2005 Alleva, LM, Yang, H, Tracey, KJ and Clark, IA (2005). High mobility group box 1 (HMGB1) protein: possible amplification signal in the pathogenesis of falciparum malaria. Transactions of the Royal Society for Tropical Medicine and Hygiene 99:171-174. 2004 Clark, IA, Alleva, LM, Mills, AC & Cowden, WB (2004). Pathogenesis of malaria and clinically similar conditions. Clinical Microbiology Reviews 17:509-539.

Side Interests

• Slow Science: http://en.wikipedia.org/wiki/Slow_Science