You are here
Dr Ann Frazier
Dr Ann Frazier has been studying various aspects of mitochondrial biology for more than 10 years, leading to over 20 peer-reviewed publications on these topics. She obtained her PhD in 2004 on mitochondrial protein transport in the yeast Saccharomyces cerevisiae from the University of Freiburg, Germany, followed by a post-doc at La Trobe University, Melbourne studying mammalian mitochondrial morphology. She joined the laboratory of Prof David Thorburn at the Murdoch Childrens Research Institute in 2009 where she currently leads a group studying mouse and cellular model systems to better understand the pathology of mitochondrial OXPHOS disorders.
Dr Frazier is active in supervising students and is a member of various professional societies, including HGSA (VIC/TAS branch committee), ANZSCDB and ASMR.
- Career Development Award Level 1, National Health and Medical Research Council, 2009
- Travel grant to attend EuroMit8 Conference (Zaragoza, Spain), Cass Foundation, 2011
- Mito Foundation Award for Excellence in Mitochondrial Research 2017
Disorders of mitochondrial energy generation cause a wide range of diseases, primarily affecting the brain and heart, and affect approximately 1/5000 individuals. Milder mitochondrial dysfunction is also implicated in the pathogenesis of common age-related neurological and cardiac diseases. The pathological mechanisms resulting in these diverse diseases are not well established. Therefore, their study at a cellular level may lead to improved treatment and greater understanding of the role of both nuclear and mitochondrial-DNA mutations in rare and common conditions. Furthermore, no effective treatments for mitochondrial disease are currently available.
Dr Frazier’s research focuses on the study of human and mouse primary cell culture models, along with stem cell models that can be differentiated into cardiac or neuronal lineages. These model systems allow for the exploration and comparison of cellular parameters that are relevant to disease pathogenesis. As well, these diverse cell models will be used to screen a variety of drug interventions that target signalling pathways affected by mitochondrial dysfunction. In conjunction with this, Dr Frazier is also exploring these treatment strategies in mouse models of mitochondrial Complex I deficiency presenting with primarily neurodegenerative or cardiac disease.
- The development and analysis of cellular models of mitochondrial disease to study pathogenic mechanisms in disease relevant cells
- Therapeutic treatment trials in a mouse model of mitochondrial neurodegenerative disease
Palmer, C.S., Osellame, L.D., Laine, D., Koutsopoulos, O.S., Frazier, A.E. & Ryan, M.T. (2011) MiD49 and MiD51, new components of the mitochondrial fission machinery. EMBO Rep. 12, 565-73.
Frazier, A.E. & Thorburn, D.R. (2012) Biochemical analyses of the electron transport chain complexes by spectrophotometry. Methods Mol. Biol. 837, 49-62.
Tucker, E.J., Wanschers, B.F., Szklarczyk, R., Mountford, H.S., Wijeyeratne, X.W., van den Brand, M.A., Leenders, A.M., Rodenburg, R.J., Reljic, B., Compton, A.G., Frazier, A.E., Bruno, D.L., Christodoulou, J., Endo, H., Ryan, M.T., Nijtmans, L.G., Huynen, M.A., Thorburn, D.R. (2013) Mutations in the UQCC1-Interacting Protein, UQCC2, Cause Human Complex III Deficiency Associated with Perturbed Cytochrome b Protein Expression. PLoS Genet. 9(12):e1004034.
Bird, M.J., Thorburn, D.R., & Frazier, A.E. (2014) Modelling biochemical features of mitochondrial neuropathology. Biochim. Biophys. Acta. 1840, 1380-92.
Bird, M.J., Needham, K., Frazier, A.E., van Rooijen, J., Leung, J., Hough, S., Denham, M., Thornton, M.E., Parish, C.L., Nayagam, B.A., Pera, M., Thorburn, D.R., Thompson, L.H., & Dottori, M. (2014) Functional characterization of Friedreich Ataxia iPS-derived Neuronal Progenitors and their integration in the adult brain. PLoS One. 9(7):e101718.
Bird, M.J., Wijeyeratne, X.W., Komen, J.C., Laskowski, A., Ryan, M.T., Thorburn, D.R. & Frazier, A.E. (2014) Neuronal and astrocyte dysfunction diverges from embryonic fibroblasts in the Ndufs4fky/fky mouse. Biosci. Rep. 34(6):e00151.
Wright, D.J., Renoir, T., Smith, Z.M., Frazier, A.E., Francis, P.S., Thorburn, D.R., McGee, S.L., Hannan, A.J. & Gray, L.J. (2015) N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington's disease. Transl. Psychiatry. 2015 Jan 6;5:e492.
Formosa, L.E., Mimaki, M., Frazier, A.E., McKenzie, M., Stait, T.L., Thorburn, D.R., Stroud, D.A., & Ryan, M.T. (2015) Characterization of mitochondrial FOXRED1 in the assembly of respiratory chain complex I. Hum. Mol. Genet. 24:2952-65.
Stroud, D.A., Maher, M.J., Lindau, C., Vögtle, F.N., Frazier, A.E., Surgenor, E., Mountford, H., Singh, A.P., Bonas, M., Oeljeklaus, S., Warscheid, B., Meisinger, C., Thorburn, D.R., & Ryan, M.T. (2015) COA6 is a mitochondrial complex IV assembly factor critical for biogenesis of mtDNA-encoded COX2. Hum. Mol. Genet. 24:5404-15.
Johnson, J., Lee, W., Frazier, A.E., Vaghjiani, V., Laskowski, A., Rodriguez, A.L., Cagnone, G.L., McKenzie, M., White, S.J., Nisbet, D.R., Thorburn, D.R.& St John, J.C. (2016) Deletion of the Complex I Subunit NDUFS4 Adversely Modulates Cellular Differentiation. Stem Cells Dev. 25:239-50.
Stiller, S.B., Höpker, J., Oeljeklaus, S., Schütze, C., Schrempp, S.G., Vent-Schmidt, J., Horvath, S.E., Frazier, A.E., Gebert, N., van der Laan, M., Bohnert, M., Warscheid, B., Pfanner, N., & Wiedemann, N. (2016) Cell Metab. 23:901-8.
Stroud, D.A., Surgenor, E.E., Formosa, L.E., Reljic, B., Frazier, A.E., Dibley, M.G., Osellame, L.D., Stait, T., Beilharz, T.H., Thorburn, D.R., Salim, A., & Ryan, M.T. (2016) Accessory subunits are integral for assembly and function of human mitochondrial complex I. Nature. 538:123-126.
Desai, R.*, Frazier, A.E.*, Durigon, R., Patel, H., Jones, A.W., Dalla Rosa, I., Lake, N.J., Compton, A.G., Mountford, H.S., Tucker, E.J., Mitchell, A.L.R., Jackson, D., Sesay, A., Di Re, M., van den Heuvel, L.P., Burke, D., Francis, D., Lunke, S., McGillivray, G., Mandelstam, S., Mochel, F., Keren, B., Jardel, C., Turner, A.M., Ian Andrews, P., Smeitink, J., Spelbrink, J.N., Heales, S.J., Kohda, M., Ohtake, A., Murayama, K., Okazaki, Y., Lombès, A., Holt, I.J.#, Thorburn, D.R.#, & Spinazzola, A.# (2017) ATAD3 gene cluster deletions cause cerebellar dysfunction associated with altered mitochondrial DNA and cholesterol metabolism. Brain. 140:1595-1610. *,#equal contribution
Kang, Y., Stroud, D.A., Baker, M.J., De Souza, D.P., Frazier, A.E., Liem, M., Tull, D., Mathivanan, S., McConville, M.J., Thorburn, D.R., Ryan, M.T., & Stojanovski, D. (2017) Sengers Syndrome-Associated Mitochondrial Acylglycerol Kinase Is a Subunit of the Human TIM22 Protein Import Complex. Mol Cell. 67:457-470.e5.
Frazier, A.E., Holt, I.J., Spinazzola, A., & Thorburn, D.R. (2017) Reply: Genotype-phenotype correlation in ATAD3A deletions: not just of scientific relevance. Brain.140(11):e67.
Frazier, A.E., Thorburn, D.R., & Compton, A.G. (2017) Mitochondrial energy generation disorders: genes, mechanisms and clues to pathology. J Biol Chem. pii: jbc.R117.809194.
Wali, J.A., Galic, S., Tan, C.Y., Gurzov, E.N., Frazier, A.E., Connor, T., Ge, J., Pappas, E.G., Stroud, D., Varanasi, L.C., Selck, C., Ryan, M.T., Thorburn, D.R., Kemp, B.E., Krishnamurthy, B., Kay, T.W., McGee, S.L., & Thomas, H.E. (2018) Cell Death Differ. 25:217-225.
- National Health and Medical Research Council
- MCRI Stem Cell Pilot funding (Genetics/Cell Biology Themes)
- MCRI Genetics Theme funding