Mangum Lab: Translational Proteomics

Researcher

Research Overview

We work on the discovery, validation, and development of new therapeutics for a range of disorders, including cancer, brain injury, and craniofacial defects. The lab is equipped with cutting-edge proteomics equipment that allows high-throughput screening for biomarker & target discovery in clinical samples. We also use complementary molecular, cellular, pre-clinical, and clinical research approaches to translate our work towards health benefit.

Our biomedical research is coupled with an entrepreneurial approach - having co-founded two startup companies, patented widely, raised investment capital for research commercialisation, and developed strategic corporate partnerships; which collectively forms a platform for effective pursuit of research translation.

Proteomics

Many drug targets and biomarkers are proteins. It therefore makes sense to study proteins when trying to understand disease mechanisms and seeking new therapeutic opportunities. Proteomics is the discipline of characterising, en masse, protein dynamics in a given (patho)physiological situation. Our lab uses proteomics as a platform technology to enable biomedical research into clinically important problems, including cancer and brain injury. Thanks to a research collaboration with Agilent Technologies, we have access to the latest in mass spectrometry equipment and proteome analysis software. This allows the lab to have end-to-end proteomics workflow capability, going from clinical sample preparation through to quantitative analysis of the proteome at a systems biology level.

Cancer

Many types of primary tumours respond well to classical surgery, radiotherapy, and chemotherapy. However, recurrent and metastatic tumours can be difficult to treat due to development of drug resistance. We are using proteomics to understand the molecular determinants of drug resistance in cancer in order to discover and target therapeutic leads for improved treatment of otherwise recalcitrant tumours. This work is in collaboration with A/Prof Fred Hollande in the Department of Pathology and Victorian Comprehensive Cancer Centre.

Stroke

Stroke causes substantial morbidity and mortality globally, and presents significant challenges to clinicians who treat these emergency cases. One such clinical challenge is understanding patient prognosis once they are stabilised and in intensive care. We are conducting clinical proteomics on cerebrospinal fluid from patients with aneurysmal subarachnoid haemorrhage to develop targets for early detection and treatment of common post-admission pathology. This work is in collaboration with A/Prof James Ziogas in the Department of Pharmacology & Therapeutics and Dr Alex Adamides in the Department of Surgery, Royal Melbourne Hospital.

We are always looking for collaborative opportunities. If something on this page piques your interest, please feel free to drop the group leader an e-mail.

Staff

Dr Dalia Ponce Garcia, Research Officer
Ms Trudi Harris, Senior Technical Officer
Ms Yunqi Bao, Masters Candidate

Collaborators

Associate Professor James Ziogas
Dr Alex Adamides
Associate Professor Fred Hollande
Professor Daniel Hoyer
Dr Laura Jacobson
Professor Alastair Stewart
Dr Graham MacKay

Funding

NHMRC
ARC
Agilent Technologies
Incisive Technologies
University of Melbourne

Research Outcomes

Patents

2018 - Brazilian patent BR 22 2012 023550.8, granted in March
2017 - US 15/422,996: UNITED STATES OF AMERICA, Divisional National Phase Filing
2016 - Canadian patent PCT/AU2011/000303 granted in July
2016 - Chinese patent 201180024864.1 granted in July
2016 - Japanese patent PCT/AU2011/000303 granted in May
2016 - Australian patent PCT/AU2011/000303 granted in April
2013 - PCT/AU2011/000303: JAPAN, National Phase Filing
2013 - 201180024864.1: CHINA, National Phase Filing
2013 - PCT/AU2011/000303: CANADA, National Phase Filing
2013 - PCT/AU2011/000303: AUSTRALIA, National Phase Filing
2013 - 11755567.2: EUROPEAN PATENT OFFICE (40 jurisdictions), National Phase Filing
2013 - 9029/DELNP/2012: INDIA, National Phase Filing
2013 - 13/501676: UNITED STATES OF AMERICA, National Phase Filing
2013 - BR 22 2012 023550.8: BRAZIL, National Phase Filing
2013 - MX/a/2012/010817: MEXICO, National Phase Filing
2013 - 10-2012-7027309: SOUTH KOREA, National Phase Filing
2013 - 9029/DELNP/2012: INDIA, National Phase Filing
2013 - 2012144398: RUSSIA, National Phase Filing
2013 - PCT/AU2011/000303: NEW ZEALAND, National Phase Filing
2011 - PCT/AU2011/000303, International PCT filing
2010 - PCT/AU2011/000303 Provisional specification filing

Research Publications

  • Alexander SPH, Roberts RE, Broughton BRS, Sobey CG, George CH, Stanford SC, Cirino G, Docherty JR, Giembycz MA, Hoyer D, Insel PA, Izzo AA, Ji Y, MacEwan DJ, Mangum J, Wonnacott S, Ahluwalia A. (2018) Goals and practicalities of immunoblotting and immunohistochemistry: A guide for submission to the British Journal of Pharmacology. Br J Pharmacol. 175:407-411.
  • Perez VA, Mangum JE, Hubbard MJ (2018) Direct evidence that KLK4 is a hydroxyapatite-binding protein. Biochem Biophys Res Commun 495:1896-1900.
  • Hubbard MJ, Mangum JE, Perez VA, Nervo GJ, Hall RK.  Molar Hypomineralisation: A call to arms for enamel researchers. Front Physiol 2017; 8: 1-6
  • Mangum JE, Kon JC, Hubbard MJ. Proteomic analysis of dental tissue microsamples. Methods Mol Biol 2017; 1537:461-479.
  • Gorasia D, Dudek N, Safavi-Hemami H, Schittenhelm R, Saunders P, Wee S, Mangum JE, Hubbard M, Purcell AW.A Prominent Role of PDIA6 in Processing of Misfolded Proinsulin. Biochim Biophys Acta 2016; 1864(6): 715-723.
  • Volpert M, Mangum JE, Jamsai D, D'Sylva R, O'Bryan MK, McIntyre P.  Eukaryotic expression, purification and structure/function analysis of native, recombinant CRISP3 from human and mouse. Sci Rep 2014; 4:4217; 1–7.
  • Hubbard MJ, McHugh NJ, Mangum JE. Exclusion of all three calbindins from a calcium-ferry role in rat enamel cells. Eur J Oral Sci 2011; 119(Suppl1): 112–119.
  • Mangum JE, Crombie FA, Kilpatrick N, Manton DJ, Hubbard MJ. Surface integrity governs the proteome of hypomineralized enamel. J Dent Res 2010; 89(10): 1160-1165
  • Mangum JE, Kon JC, and Hubbard MJ. Proteomic analysis of dental tissue microsamples. Methods Mol Biol 2010; 666: 309-325.
  • Shnyder SD, Mangum JE, Hubbard MJ. Triplex profiling of functionally distinct chaperones (ERp29/PDI/BiP) reveals marked heterogeneity of the endoplasmic reticulum proteome in cancer. J Proteome Res 2008; 7(8): 3364-3372.
  • Mangum JE, Veith PD, Reynolds EC, Hubbard MJ. Towards second-generation proteome analysis of murine enamel-forming cells. Eur J Oral Sci 2006; 114(Suppl 1): 259-265.
  • Mangum JE, Farlie PG, Hubbard MJ. Proteomic profiling of facial development in chick embryos. Proteomics 2005; 5(10): 2542-2550.
  • Turnbull CI, Looi K, Mangum JE, Meyer M, Sayer RJ, Hubbard MJ. Calbindin independence of calcium transport in developing teeth contradicts the calcium ferry dogma. J Biol Chem 2004; 279(53): 55850-55854.
  • Hubbard MJ, Mangum JE, McHugh NJ. Purification and biochemical characterization of native ERp29 from rat liver. Biochem J 2004; 383(Pt. 3): 589-597.
  • Brown CM, Jacobs GH, Schrieber MJ, Mangum JE, et al. Using bioinformatics to investigate post-transcriptional control of gene expression. NZ BioScience 1999; 7: 11-12.

Research Projects



Faculty Research Themes

Cancer

School Research Themes

Cancer in Biomedicine, Therapeutics & Translation



Key Contact

For further information about this research, please contact Dr Jon Mangum

Department / Centre

Pharmacology and Therapeutics

Unit / Centre

Mangum Lab: Translational Proteomics


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