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Network Member Profile

Current Field of Study

• My research interests lie in understanding the cellular mechanisms of oxygen sensing in metazoan, in particular the genomic response to hypoxia. Hypoxia is both an environmental stress and one associated with numerous disease pathologies. Importantly, hypoxia is also an important cue for the normal development of vasculature in organisms as diverse as mammals and insects, and disruptions to normal oxygen levels or specific components cause developmental abnormalities. The key components of the genomic response to hypoxia have been identified in mammals and few other organisms, and include the hypoxia inducible transcription factors (HIFs) and associated oxygen-sensing prolyl and asparaginyl hydroxylases. However, their specific cellular and physiological roles of each of these remain to be fully ascertained, particularly in development. This is one area of research focus, in particular the role of the HIF asparaginyl hydroxylase FIH-1 and the identity and role of hydroxylation of non-HIF substrates such as Notch.

Australian Collaborators

• Dr Michael Lardelli (School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA)
• Dr Grant Booker (School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA)
• Assoc. Prof. Murray Whitelaw (School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA)
• Dr Jeremy Thompson (Department of Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA)
• Dr Andrew Zannettino (Myeloma & Mesenchymal Research Laboratory, Hanson Institute, IMVS, Adelaide)
• Prof. Jeff Gorman (Queensland Institute for Medical research, Brisbane, QLD)
• Assoc. Prof. Jean-Pierre Levesque (Mater Medical Research Institute, South Brisbane, QLD).
  
  

International Collaborators

• Prof. Lorenz Poellinger & Prof. Urban Lendahl (Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden)
• Dr Peppi Karppinen (Department of Medical Biochemistry and Molecular Biology, University of Oulu, Finland)
• Dr Eric Metzen (Institute of Physiology, University of Luebeck, Luebeck, Germany)
• Assoc. Prof Michael Raghunath (Faculty of Engineering, National University of Singapore, Singapore)
• Prof. Randall Johnson (Division of Biological Sciences, University of California San Diego, USA)
• Dr Gail Walkinshaw (Fibrogen Inc., San Francisco, USA)
  

Recent Publications

Lando, D., Peet, D.J., Whelan, D.A., Gorman, J.J., and Whitelaw, M.L. Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch. (2002) Science, 295, 858-861.

Zheng X.*, Linke S.*, Dias J., Zheng X., Gradin K., Wallis T.P., Hamilton B.R.,Gustafsson M., Ruas J.L., Wilkins S., Bilton R.L., Brismar K., Whitelaw M.L.,Pereira T., Gorman J.J.§, Ericson J., Peet D.J., Lendahl U., and Poellinger L. Interaction with factor-inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways. (2008) Proc. Natl Acad. Sci. USA. 105:3368-73.

Lisy K., Peet D.J. Turn me on: regulating HIF transcriptional activity. (2008).Cell Death Differ. 15:642-915:805.

Linke S., Hampton-Smith, R.J. and Peet D.J. Characterisation of ankyrin-repeat containing proteins as substrates of the asparaginyl hydroxylase Factor Inhibiting HIF (FIH-1). (2007) Methods Enzymol. 435:61-85.

Hampton-Smith R.J. and Peet D.J. Hypoxia Inducible Factor. In McGraw-Hill Yearbook of Science and Technology 2007, The McGraw-Hill Editorial Staff, ed. (McGraw-Hill, USA), p108-111.

Bracken C.P., Fedele A.O., Linke S., Balrak W., Lisy K., Whitelaw M.L., Peet D.J. Cell-specific Regulation of Hypoxia-inducible Factor (HIF)-1{alpha} and HIF-2{alpha} Stabilization and Transactivation in a Graded Oxygen Environment. (2006) J Biol Chem. 281:22575-85.

Peet, D.J. and Linke, S., Regulation of HIF:asparaginyl hydroxylation. (2006) In Signalling Pathways in Acute Oxygen Sensing, Novartis Foundation Symposium No. 272, D. J. Chadwick and J.Goode, ed. (Weinheim, Germany: Wiley-VCH Verlag GmbH), p37-53.

Bracken, C.P., Whitelaw, M.L., and Peet, D.J. Activity of Hypoxia-Inducible Factor 2? (HIF-2?) is regulated by association with the NF-?B essential modulator (NEMO / IKK?).(2005) J. Biol. Chem. 280:14240-14251.

Linke, S., Stojkoski, C., Kewley, R.J., Booker, G.W., Whitelaw, M.L., and Peet, D.J. Substrate requirements of the oxygen-sensing asparaginyl hydroxylase Factor Inhibiting HIF. (2004) J. Biol. Chem. 279, 14391-14397.

Peet,D.J., Lando, D., Whelan, D.A., Whitelaw, M.L. Gorman, J.J., Oxygen-Dependent Asparagine Hydroxylation. (2004) Methods Enzymol. 381:467-87.

Lees, M.J., Peet, D.J., and Whitelaw, M.L. Defining the role for XAP2 in stabilisation of the dioxin receptor. (2003) J. Biol. Chem. 278: 35878-88.

Bracken, C.P., Whitelaw, M.L. and Peet, D.J. The Hypoxia-Inducible Factors: key transcriptional regulators of hypoxic response. (2003) Cell. Mol. Life Sci. 60:1376-1393.

Lando, D., Gorman, J.J., Whitelaw, M.L. and Peet, D.J. Oxygen-dependent regulation of hypoxia-inducible factors by prolyl and asparaginyl hydroxylases. (2003) Eur. J. Biochem., 270, 781-790.

Fedele, A.O., Whitelaw, M.L. and Peet, D.J. Regulation of gene expression by the hypoxia inducible factors. (2002) Mol. Interv. 2:229-243.

Lando*, D., Peet*, D.J., Gorman, J.J., Whelan, D.A., Whitelaw, M. L. and Bruick, R.K. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of Hypoxia Inducible Factor. (2002) Genes Dev. 16, 1466-1471 (*joint first authors).

Lando, D., Peet, D.J., Pongratz, I., and Whitelaw, M.L. Mammalian two-hybrid assay showing redox control of HIF-like factor. (2002) Methods Enzymol. 53, 3-10.