Professor Christina Mitchell

Head, School of Biomedical Sciences

Telephone: +61-3-9905 5238 Facsimile:   +61-3-9905 9324 Office:         Room D426, Building 13D Email: christina.mitchell@med.monash.edu.au

Professor Christina Mitchell trained as a physician scientist specialising in clinical hematology. She received her medical training from Melbourne University and consultant training in Hematology at the Alfred Hospital Melbourne. Her advanced clinical training in Hematology included a Ph.D. characterizing the natural anticoagulants protein C and protein S. Her post-doctoral studies were undertaken in the field of intracellular signalling in Prof. Phil Majerus's laboratory at Washington University Medical School, St Louis USA. In 1991 she returned to Australia and became an independent investigator at the Department of Medicine, Box Hill Hospital. In 1999 she was appointed Professor and Head of the Department of Biochemistry and Molecular Biology, Monash University.

Research Focus

The research group led by Professor Mitchell is currently pursuing the identification and characterization of novel proteins that regulate cell growth and differentiation. The team has two major fields of research.

A Characterization of phosphoinositide phosphatases that regulate cell growth.

The laboratory has recently cloned and is currently characterizing several lipid phosphatases that terminate signals generated by the proto-oncogene PI 3-kinase. These projects aim to determine the intracellular location of these enzymes using real time imaging in live cells, characterize substrate specificity and investigate the effect on cell growth and differentiation in various cellular models, in which these signal terminating enzymes are over, or under expressed

B Characterization of novel adapter proteins SLIM 1-3 (FHL1-3): role in muscle differentiation and cardiac failure.

We have cloned and characterized a recently identified family of proteins, comprising four and a half LIM domains, which are predominantly expressed in skeletal muscle. The proteins called SLIM 1, 2 and 3 may bind and regulate signaling proteins at specific sites within the cell, during muscle differentiation. Preliminary evidence suggests a distinct isoform SLIMMER may shuttle from the nucleus to the cytoplasm during muscle differentiation. Work in the laboratory is concentrating on determining the intracellular location of these novel adapter proteins in skeletal and cardiac muscle and the role these signaling proteins play in human diseases such as heart failure and muscular dystrophy.

Research Links

Intracellular signalling and cancer

Recent Selected Publications

Dyson JN, O'Malley CJ, Becanovic J, Munday AD, Berndt MC, Coghill ID, Nandurkar HH, Ooms LM and Mitchell CA.  (2001) The SH2 containing inositol polyphosphate 5-phosphatase, SHIP-2, binds filamin and regulates submembraneous actin. J Cell Biol 155, 1065-1079. (IF13)

Dyson JM, Munday AD, Kong AM, Huysmans RD, Matzaris M, Layton MJ, Nandurkar HH, Berndt MC and Mitchell CA.  (2003) SHIP-2 forms a tetrameric complex with filamin, actin, and GPIb-IX-V.  Localization of SHIP-2 to the activated platelet actin cytoskeleton. Blood 102, 940-948. (IF 10)

Nandurkar HH, Layton M, Laporte J, Selan C, Corcoran L, Caldwell KK, Mochizuki Y, Majerus PW and Mitchell CA.  (2003) Identification of myotubulin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adpater protein, 3-PAP. Proc Natl Acad Sci USA 100, 8660-8665. (IF 11)

McGrath MJ, Mitchell CA, Coghill ID, Robinson PA and Brown S.  (2003) Skeletal muscle LIM protein (SLIM1/FHL1) induces alpha 5 beta 1- integrin dependent myocyte elongation Am J Physiol Cell Physiol 285, C1513-26.

Ooms LM, Fedele CG, Ivetac I, Astle MV, Pearson RB, Layton MJ, Forrai A,  Nandurkar HH and Mitchell CA.  (2006) The inositol polyphosphate 5-phosphatase, PIPP, is a novel regulator of phosphoinositide 3-kinase-dependent neurite elongation. Mol Biol Cell 17, 607-22. (IF 7.5)

McGrath MJ, Cottle DL, Nguyen MA, Dyson JM, Coghill ID, Robinson PA, Holdsworth M, Cowling BS, Hardeman EC, Mitchell CA and Brown S.  (2006) Four and half LIM protein 1 binds myosin-binding protein C and regulates myosin filament assembly and sarcomere formation. J Biol Chem 17, 7666-83. (IF 6)

Kong AM, Horan KA, Sriratana A, Bailey CG, Collyer LJ, Nandurkar HH, Shisheva A, Layton M, Rasko JEJ, Rowe T and Mitchell CA.  (2006) Phosphatidylinositol (3) phosphate is generated at the plasma membrane by inositol polyphosphate 5-phosphatase hydrolysis of phosphatidylinositol (3,5) bisphosphate. Mol Cell Biol 26,6065-81. (IF 7.5)

Cottle D, McGrath M, Cowling B, Brown S and Mitchell CA.  (2007) FHL3 binds MyoD and negatively regulates myotube formation. J Cell Sci 120, 1423-35. (IF 7)

Wiradjaja F, Ooms LM, Tahirovic S, Kuhne D, Devenish RJ, Munn AL, Piper RC, Mayinger P and Mitchell CA.  (2007) Inactivation of the phosphoinositide phosphatases Sac1p and Inp54p leads to accumulation of PtdIns(4,5)P2 on vacuole membranes and vacuolar fusion defects. J Biol Chem 282, 16295-307.  (IF 6)

Horan KA, Watanabe KI, Kong AM, Bailey CG, Rasko JE, Sasaki T and Mitchell CA.  (2007) Regulation of Fc{gamma}R-stimulated phagocytosis by the 72 kDa inositol polyphosphate 5-phosphatase:  SHIP1, but not the 72 kDa 5-phosphatase, regulates complement receptor-3-mediated phagocytosis, by differential recruitment of these 5-phosphatases to the phagocytic cup.  Blood. 110, 4480-91. (IF 10.3)

Waters JE, Astle MV, Ooms LM, Balamatsias D, Gurung R, and Mitchell CA. (2008) P-Rex1, a multidomain protein that regulates neurite differentiation. J Cell Sci 121, 2892-903. (IF 7)

Cowling BS, Nguyen M-A, McGrath MJ, Cottle DL, Kee AJ, Brown S, Schessl J, Zou Y, Joya J, Bönnemann CG, Hardeman EC and Mitchell CA.  Identification of FHL1 as a novel regulator of skeletal muscle mass: implications for human myopathy. J Cell Biol (IF 11) (in press).