BS(MIT), MS, PhD(Washington)
Professor Anne La Flamme is a senior immunologist at Victoria University of Wellington who has been a research consultant for the Malaghan Institute since 2003. Since 2008 she has been the leader of our multiple sclerosis research programme.
Anne's extensive research career has spanned the University of Washington, Cornell University, and the Whitehead Biomedical Research Institute.
My primary research interest is in the immune regulation of disease. In particular, my research focuses on the pivotal role of one specific immune cell, the macrophage, in the regulation of pro-inflammatory diseases such as multiple sclerosis. These studies investigate the factors that regulate macrophage activation to induce or suppress disease. Recent work, in collaboration with other New Zealand and international researchers, is aimed at identifying new therapeutic targets and drugs to treat multiple sclerosis.
Additionally, I am investigating several aspects of schistosomiasis, a parasitic worm infection. This disease affects over 200 million people worldwide, and one of the applied goals of this research is to identify and develop biomarkers that predict the development of severe disease in patients. Finally, in partnership with other researchers in the Allan Wilson Centre, I am involved in elucidating the immune responses of tuatara.
Targeting macrophage activation for the treatment of MS
Contributors: Dr Anne La Flamme, Sarrabeth Stone, Delgertsetseg Chuluundorj, DrScottHarding (CCDHB) collaborating with Dr Jacquie Orian (LaTrobe University)
Macrophages are multifunctional immune cells and are key mediators of inflammatory immune processes. During inflammation the immune 'climate' of an organism shapes the type of immune response that develops and directs immune cells such as macrophages to promote or resolve disease.
Malaghan Institute Research Associate Dr Anne La Flamme and colleagues have shown that treatments that alter a macrophage's state of activation, and thus alter the immune climate, can prevent central nervous system inflammation and progressive paralysis in the murine model of human MS - experimental autoimmune encephalomyelitis (EAE).
Identification of the pathway(s) by which these macrophage altering treatments prevent disease may uncover much-needed therapeutic targets to inhibit or reduce the severity of MS.
Investigating immune regulation of microglial function
Contributors: Sarrabeth Stone, Dr Anne La Flamme collaborating with Assoc Prof Bronwen Connor (University of Auckland)
Immune cells including T cells, macrophages, and microglia (brain-resident macrophages) are responsible for the damage to the nerves and subsequent clinical features of MS.
While many current MS treatments target T cells, because microglia are involved in controlling central nervous system inflammation and damage, microglia may also be a valuable target for new therapies.
Dr Anne La Flamme and colleagues are investigating the immune factors that regulate microglia function in the brain using the EAE model of MS, in the hope that targeting these factors will prevent central nervous system inflammation and damage.
Exploiting anti-cancer and immune-modulating drugs for the treatment of MS
Contributors: Marie Kharkrang (VUW), Dr Anne La Flamme, collaborating with Prof John Miller & Assoc Prof Peter Northcote (Victoria University of Wellington) and David O'Sullivan & Assoc Prof Bronwen Connor (The University of Auckland)
Current disease-modifying therapies used to treat individuals with MS have variable efficacy in reducing the neurological and physical disability associated with the disease.
Recently Dr La Flamme's research group have demonstrated that drugs that prevent cellular proliferation, such as those used to treat cancer patients or immune-modulatory drugs that work to suppress immune responses, are also effective at reducing the incidence and severity of MS in experimental disease models.
Dr La Flamme is currently investigating the potential of these classes of compounds for treating MS with the hope that the use of drugs that are already in clinical practice, or are in the process of gaining FDA approval for clinical use, will accelerate the path from drug design to clinical application.
A key role for blood monocytes in EAE
Contributors: Dr Clare Slaney, Aras Toker, Dr Anne La Flamme, Assoc Prof Thomas Bäckström, Dr Jacquie Harper, collaborating with Prof John Fraser (The University of Auckland)
Experimental autoimmune encephalomyelitis (EAE) is a well established murine model of multiple sclerosis (MS) that has been used by scientists at the Malaghan Institute to better understand the causes of MS, and to test the therapeutic potential of compounds designed to halt its progression. An important outcome of this work has been the identification of a key role for blood monocytes in maintaining immune tolerance in EAE.
The monocytes were shown to suppress inflammatoryT cell responses in naive mice but lost this function when EAE was induced.
The MS drug Glatiramer acetate was shown to be taken up by the monocytes and cells exposed to the drug demonstrated increased intrinsic T cell suppressor activity. Similar outcomes were obtained with an immune-modifying superantigen compound developed by Prof John Fraser.
These findings have important clinical implications for the design of novel immunotherapeutic agents that target specific cell types for the treatment of individuals with MS.
Chuluundorj D, Harding SA, Abernethy D, La Flamme AC (2014) Expansion and preferential activation of the CD14+CD16+ monocyte subset during multiple sclerosis. Immunol Cell Biol
White M, Webster G, O’Sullivan D, Stone S, La Flamme AC (2014) Targeting innate receptors with MIS416 reshapes Th responses and suppresses CNS disease in a mouse model of multiple sclerosis. PLoS One
Johnston LR, Larsen PD, La Flamme AC, Harding SA (2013) Methodological considerations for the assessment of ADP induced platelet aggregation using the Multiplate® analyser. Platelets
Johnston LR, Larsen PD, La Flamme AC, Michel JM, Harding SA (2013) Suboptimal response to clopidogrel and the effect of prasugrel in acute coronary syndromes. Int J Cardiol
O’Sullivan D, Miller JH, Northcote PT, La Flamme AC (2013) Microtubule-stabilizing agents delay the onset of EAE through inhibition of migration. Immunol Cell Biol
La Flamme AC, Kharkrang M, Stone S, Mirmoeini S, Chuluundorj D, Kyle R (2012) Type II-activated murine macrophages produce IL-4. PLoS One.
Manivannan B, Jordan TW, Secor WE, La Flamme AC (2012) Proteomic changes at eight weeks after infection are associated with chronic liver pathology in experimental schistosomiasis. J Proteomics.
Meyer KJ, Singh AJ, Cameron A, Tan AS, Leahy DC, O'Sullivan D, Joshi P, La Flamme AC, Northcote PT, Berridge MV, Miller JH (2012) Mitochondrial genome-knockout cells demonstrate a dual mechanism of action for the electron transport complex I inhibitor mycothiazole. Mar Drugs.
Manivannan B, Rawson P, Jordan TW, Karanja DM, Mwinzi PN, Secor WE, La Flamme AC (2011) Identification of cytokeratin-18 as a biomarker of mouse and human hepatosplenic schistosomiasis. Infect Immun.
Slaney CY, Toker A, La Flamme AC, Bäckström BT, Harper JL (2011) Naïve blood monocytes suppress T-cell function. A possible mechanism for protection from autoimmunity. Immunol Cell Biol.
Wilms A, O'Sullivan D, Chan A, Chandrahasen C, Paterson I, Northcote PT, La Flamme AC, Miller JH (2011) Synergistic interactions between perloruside A and other microtuble-stabilizing and destablizing agents in cultured human ovarian carcinoma cells and murine T cells. Cancer Chemother Pharmacol.
La Flamme AC, de Thierry D, ONeill S, Miller H (2010) Toll-like receptor responses in tuatara. NZ J Zoology.
Manivannan B, Rawson P, Jordan TW, Secor E, La Flamme AC (2010) Differential patterns of liver proteins in experimental murine hepatosplenic schistosomiasis. Infect Immun.
Robinson MJ, Ronchese F, Miller JH, La Flamme AC (2010) Paclitaxel inhibits killing by murine cytotoxic T lymphocytes in vivo but not in vitro. Immunol Cell Biol.
Keating P, OSullivan D, Tierney JB, Kenwright D, Miromoeini S, Mawasse L, Brombacher F, La Flamme AC (2009) Protection from EAE by IL-4Ralpha-- macrophages depends upon T regulatory cell involvement. Immunol Cell Biol.
Crume KP, OSullivan D, Miller JH, Northcote PT, La Flamme AC (2009) Delaying the onset of experimental autoimmune encephalomyelitis with the microtubule-stabilizing compounds, paclitaxel and peloruside A. J Leuk Biol.
Tierney JB, Kharkrang M, La Flamme AC (2009) Type II-activated macrophages suppress the development of experimental autoimmune encephalomyelitis. Immunol Cell Biol.