Dr Kristina Cook

Research Fellow
Northern Clinical School
University of Sydney

Telephone 02 8627 4858

Website Google Scholar profile

Map

Biographical details

Dr Kristina Cook is a research fellow in the Charles Perkins Centre. Dr Cook completed her D.Phil. in Chemical Biology at the University of Oxford in 2010 in a collaborative program with the NIH (USA) as an OxCam Biomedical Research Scholar.

She graduated Summa Cum Laude from San Diego State University in 2005, with a B.S. in Molecular and Cellular Biology and a minor in Chemistry (awarded a ‘distinction’, the highest honour).

Dr Cook's work has been extensively cited (> 750 times) and is published in many top journals including Nature Communications, Journal of Biological Chemistry, Blood, Journal of the American Chemical Society, Antioxidants and Redox Signaling, among others.

Dr Cook’s review on angiogenesis inhibitors is cited by the National Cancer Institute’s official patient guide to angiogenesis inhibitors (NIH, USA) and by UpToDate, a physician’s resource.

Research interests

Dr Cook’s research aims are to understand the regulation of hypoxia inducible factor (HIF), a transcription factor activated by hypoxia and involved in cancer development and progression, and to develop anti-cancer drugs that inhibit HIF. She has a particular interest in understanding the role of HIF and intermittent hypoxia in tumours linked to obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is increasingly prevalent in the adult population and is commonly associated with stroke and cardiovascular disease. It is characterised by episodic obstruction of the upper airway, resulting in intermittent hypoxia and cyclical decreases in blood oxygen followed by re-oxygenation.

Recent epidemiological studies have shown that OSA patients have higher rates of cancer and cancer mortality, yet the underlying mechanisms are poorly understood. Dr Cook’s work focuses on the fundamental mechanisms underpinning this association and in particular the role of intermittent hypoxia.

While at Oxford and the NIH she studied the regulation of HIF in tumour hypoxia, and identified a new class of HIF-targeting drugs. These small molecules inhibit HIF activity, decreasing expression of HIF-controlled genes, and reduce blood vessel growth in angiogenesis models. They also decrease tumour growth in mouse models. This work led to Dr Cook spearheading the design of a high-throughput drug screen to identify new HIF inhibitors at the NIH. The screen was highly successful and isolated 27 novel inhibitors.

Additional areas of interest include studying the regulation of protein function through post-translational modifications, including phosphorylation, hydroxylation, and allosteric disulfide bonds. Dr Cook discovered that the mast cell protease, ß-tryptase, important in allergies and anaphylaxis, is regulated by an allosteric disulfide bond. This finding has led to ongoing studies into the evolutionary conservation of this regulatory mechanism in a wide range of related serine proteases, including many of the coagulation factors.

Awards and honours

  • Cancer Institute NSW Early Career Fellowship (2017-2020).
  • University of Sydney Fellowship (2017).
  • Females in Science award (2016). Bank of Queensland and Centenary Institute.
  • Career Advancement Award (2015). UNSW.
  • AACR Busch Scholar in Training award (2008)
  • NIH/NCI Director’s Innovation Award (2007) with Dr William D Figg.
  • NIH OxCam Biomedical Research Scholar award (2005-2009).
  • Howell Undergraduate Research Fellowship (2004).
  • IRA International Travel Scholarship (2004).
  • First place poster. MBRS Undergraduate Research Symposium; San Diego, Ca (2004).
  • Ronald Dietz Scholarship. SDSU College of Sciences (2004).
  • The Harry E. Hamber Memorial Scholarship. SDSU (2004).
  • Scholarship Award from Mortarboard Honor Society. SDSU (2004).
  • Mabel Myers Memorial Scholarship. SDSU (2004).
  • Wilmia Tyler Trott Memorial Scholarship. SDSU (2004).
  • Mabel Myers Memorial Scholarship. SDSU (2003).
  • The Harry E. Hamber Memorial Scholarship. Biology Dept. and Chemistry Dept. SDSU (2002).

Publications

  • SA Read, KS O'Connor, V Suppiah, CLE Ahlenstiel, S Obeid,KM Cook, A Cunningham, MW Douglas, PJ Hogg, D Booth, J George, G Ahlenstiel.Zinc is a potent and specific inhibitor of IFN-λ3 signalling. 2017.Nature Communications.8: 15245.
  • RH Bekendam, P Bendapudi, L Lin, P Nag, DR Kennedy, J Chiu, KM Cook, B Furie, M Huang, PJ Hogg, R Flaumenhaft. A substrate-driven allosteric switch that enhances PDI catalytic activity. 2016. Nature Communications. 7: 12579.
  • AKL Goey, CH Chau, TM Sissung, KM Cook, DJ Venzon, A Castro, TR Ransom, CJ Henrich, TC McKee, JB McMahon, T Grkovic, MM Cadelis, BR Copp, KR Gustafson, and WD Figg. Screening and Biological Effects of Marine Pyrroloiminoquinone Alkaloids: Potential Inhibitors of the HIF-1a/p300 Interaction. 2016. Journal of Natural Products. In Press.
  • STS Chan, PR Patel, TR Ransom, CJ Henrich, TC McKee, AKL Goey,KM Cook, WD Figg, JB McMahon, MJ Schnermann, KR Gustafson.Structural Elucidation and Synthesis of Eudistidine A: An Unusual Polycyclic Marine Alkaloid that Blocks Interaction of the Protein Binding Domains of p300 and HIF-1a. 2015. Journal of the American Chemical Society. 137:16, 5569-5575.
  • MKP Jayatunga, S Thompson, TC McKee, MC Chan, KM Reece, AP Hardy, PT Sedan, KM Cook, JB McMahon, WD Figg, CJ Schofield and AD Hamilton. Inhibition of the HIF1a-p300 interaction by quinine and indandione mediated ejection of structural zinc (II). 2015. European Journal of Medicinal Chemistry. 94: 509-516.
  • D Butera*,KM Cook*, J Chiu, JWH Wong and PJ Hogg. Control of blood proteins by functional disulfide bonds. 2014. Blood. 123:13, 2000-2007. *joint first author
  • KM Reece, ED Richardson, KM Cook, TJ Campbell, ST Pisle, AJ Holly, DJ Venzon, DJ Liewehr, CH Chau, DK Price and WD Figg. Epidithiodiketopiperazines (ETPs) exhibit in vitro antiangiogenic and in vivo antitumor activity by disrupting the HIF-1a/p300 complex in a preclinical model of prostate cancer. 2014. Molecular Cancer. 13:1, 91-103.
  • KM Cook, HP McNeil and PJ Hogg. Allosteric control of ßII-tryptase by a redox active disulfide bond. 2013. Journal of Biological Chemistry. 288: 48. 34920-34929.
  • KM Cookand PJ Hogg. Posttranslational control of protein function by disulfide bond cleavage. 2013. Antioxidants & Redox Signaling. 18:15, 1987-2015.
  • KM Cookand WD Figg. Angiogenesis Inhibitors: Current Strategies and Future Prospects. 2010. CA: A Cancer Journal for Clinicians, 60:4, 222-243. *Cited by NCI/NIH fact sheet on angiogenesis inhibitors for patients and cited by UptoDate.
  • KM Cook, ST Hilton, J Mecinovic, WD Figg and CJ Schofield. Epidithiodiketopiperazines Block the Interaction Between Hypoxia-inducible Factor-1a (HIF-1a) and p300 by a Zinc Ejection Mechanism. 2009. Journal of Biological Chemistry, 284:39, 26831-26838.
  • ML Coleman, MA McDonough, KS Hewitson, C Coles, J Mecinovic, M Edelmann, KM Cook, ME Cockman, DE Lancaster, BM Kessler, NJ Oldham, PJ Ratcliffe, and CJ Schofield. Asparaginyl Hydroxylation of the Notch Ankyrin Repeat Domain by Factor Inhibiting Hypoxia Inducible Factor.2007.Journal of Biological Chemistry, 282:33, 24027-24038.
  • CL Carroll, JVC Johnston, A Kekec, JD Brown, E Perry, J Cajica, I Medina, KM Cook, R Corral, PS Pan, SR McAlpine. Synthesis and Cytotoxicity of Novel Sansalvamide A Derivatives. 2005.Organic Letters, 7:16, 3481-3484.
  • LA Liotta, I Medina, JL Robinson, CL Carroll, PS Pan, R Corral, JVC Johnston, KM Cook, FA Curtis, GJ Sharples; SR McAlpine. Novel Antibiotics: Second Generation Macrocyclic Peptides Designed to Trap Holliday Junctions. 2004. Tetrahedron Letters 45, 8447-8450.

Book Chapters

  • KM Cook, and CJ Schofield. Therapeutic Strategies that Target the HIF System (Chapter 32). 2008. Figg WD, Folkman J (Editors). Angiogenesis: An Integrative Approach from Science to Medicine. Springer, Boston, MA.

Selected grants

2017

  • Losing Sleep Over Cancer: Regulation of HIF-1 in Sleep Apnoea and Tumour Development; Cook K; Cancer Institute New South Wales/Early Career Fellowship.
  • Losing sleep over cancer: The role of HIF in obstructive sleep apnoea and tumour development; Cook K; DVC Research/Postdoctoral Research Fellowship Scheme.

Selected publications

Download citations: PDF RTF Endnote

Journals

  • Goey, A., Chau, C., Sissung, T., Cook, K., Venzon, D., Castro, A., Ransom, T., Henrich, C., McKee, T., et al (2016). Screening and Biological Effects of Marine Pyrroloiminoquinone Alkaloids: Potential Inhibitors of the HIF-1alpha/p300 Interaction. Journal of Natural Products, 79(5), 1267-1275. [More Information]
  • Jayatunga, M., Thompson, S., McKee, T., Chan, M., Reece, K., Hardy, A., Sekirnik, R., Seden, P., Cook, K., et al (2015). Inhibition of the HIF1alpha-p300 interaction by quinone- and indandione-mediated ejection of structural Zn(II). European Journal of Medicinal Chemistry, 94, 509-516. [More Information]
  • Chan, S., Patel, P., Ransom, T., Henrich, C., McKee, T., Goey, A., Cook, K., Figg, W., McMahon, J., et al (2015). Structural Elucidation and Synthesis of Eudistidine A: An Unusual Polycyclic Marine Alkaloid that Blocks Interaction of the Protein Binding Domains of p300 and HIF-1alpha. Journal of the American Chemical Society, 137(16), 5569-5575. [More Information]
  • Butera, D., Cook, K., Chiu, J., Wong, J., Hogg, P. (2014). Control of blood proteins by functional disulfide bonds. Blood, 123(13), 2000-2007. [More Information]
  • Reece, K., Richardson, E., Cook, K., Campbell, T., Pisle, S., Holly, A., Venzon, D., Liewehr, D., Chau, C., et, A. (2014). Epidithiodiketopiperazines (ETPs) exhibit in vitro antiangiogenic and in vivo antitumor activity by disrupting the HIF-1alpha/p300 complex in a preclinical model of prostate cancer. Molecular Cancer, 13(1), 1-12. [More Information]
  • Cook, K., McNeil, H., Hogg, P. (2013). Allosteric control of betaII-tryptase by a redox active disulfide bond. The Journal of Biological Chemistry, 288(48), 34920-34929. [More Information]
  • Cook, K., Hogg, P. (2013). Post-translational control of protein function by disulfide bond cleavage. Antioxidants & Redox Signaling, 18(15), 1987-2015. [More Information]

2016

  • Goey, A., Chau, C., Sissung, T., Cook, K., Venzon, D., Castro, A., Ransom, T., Henrich, C., McKee, T., et al (2016). Screening and Biological Effects of Marine Pyrroloiminoquinone Alkaloids: Potential Inhibitors of the HIF-1alpha/p300 Interaction. Journal of Natural Products, 79(5), 1267-1275. [More Information]

2015

  • Jayatunga, M., Thompson, S., McKee, T., Chan, M., Reece, K., Hardy, A., Sekirnik, R., Seden, P., Cook, K., et al (2015). Inhibition of the HIF1alpha-p300 interaction by quinone- and indandione-mediated ejection of structural Zn(II). European Journal of Medicinal Chemistry, 94, 509-516. [More Information]
  • Chan, S., Patel, P., Ransom, T., Henrich, C., McKee, T., Goey, A., Cook, K., Figg, W., McMahon, J., et al (2015). Structural Elucidation and Synthesis of Eudistidine A: An Unusual Polycyclic Marine Alkaloid that Blocks Interaction of the Protein Binding Domains of p300 and HIF-1alpha. Journal of the American Chemical Society, 137(16), 5569-5575. [More Information]

2014

  • Butera, D., Cook, K., Chiu, J., Wong, J., Hogg, P. (2014). Control of blood proteins by functional disulfide bonds. Blood, 123(13), 2000-2007. [More Information]
  • Reece, K., Richardson, E., Cook, K., Campbell, T., Pisle, S., Holly, A., Venzon, D., Liewehr, D., Chau, C., et, A. (2014). Epidithiodiketopiperazines (ETPs) exhibit in vitro antiangiogenic and in vivo antitumor activity by disrupting the HIF-1alpha/p300 complex in a preclinical model of prostate cancer. Molecular Cancer, 13(1), 1-12. [More Information]

2013

  • Cook, K., McNeil, H., Hogg, P. (2013). Allosteric control of betaII-tryptase by a redox active disulfide bond. The Journal of Biological Chemistry, 288(48), 34920-34929. [More Information]
  • Cook, K., Hogg, P. (2013). Post-translational control of protein function by disulfide bond cleavage. Antioxidants & Redox Signaling, 18(15), 1987-2015. [More Information]

To update your profile click here. For support on your academic profile contact .