Profile for Associate Professor Mark Molloy

Research Interests

My lab uses proteomic technologies for cancer research.  Our research sits at the interface of biochemistry/cell biology/analytical chemistry/clinical chemistry.  We have collaborators in clinical medicine, organic chemistry and molecular cell biology.  Quantitative mass spectrometry techniques are heavily used in my group, but other important bioanalytical techniques including electrophoresis and chromatography are also applied.  Most of my research utilises the state-of-the-art infrastructure located within the Australian Proteome Analysis Facility (APAF) at Macquarie University.

There are honours and post-graduate research opportunities in the following projects.

1. Protein biomarkers of colorectal cancer tumours

   In collaboration with Prof. S. Clarke at Concord Hospital we investigate tumour specimens to identify prognostic protein biomarkers of patient survival.  In this study, iTRAQ mass spectrometry is used to identify proteins and measure their levels from different patient samples. This provides us with knowledge of differentially expressed proteins that can be further evaluated by other classical methods such as immunohistochemistry.  This is a translational medical research project that has potential to change clinical treatment practises.  This project would suit students with cell biology/biochemistry backgrounds.

2. Plasma biomarkers for chemotherapy prediction

   Dosing for cancer patients that receive chemotherapy is based on the patients body-surface area, however, this is a crude indicator to predict efficacy, with many patients either under or over-dosed.  Approximately 20% of patients develop treatment related chemotoxicity and only 50% of patients derive benefit from chemotherapy.  This project aims for early identification of these patient sub-groups by examining changes in their plasma proteome associated with treatment.  We use selected reaction monitoring mass spectrometry for multiplexed quantitation of protein biomarker candidates and correlate these with clinical outcomes.  This is a translational medical research project that has potential to change clinical treatment practises.  This project would suit students with strong biochemistry/analytical chemistry background.

3. Phosphoproteomics and protein-interactomics in cancer signalling

   To unravel cell signalling pathways we have established methods to profile the phosphoproteome.  We are interested in identifying novel signalling routes associated with transforming growth factor beta pathways, as the cytokine illicit both pro-apotopic and pro-growth responses in certain tumours.  Protein-protein interactions are fundamental processes for cell signalling.  Projects in this area use molecular biology, protein expression and immunoprecipitation methods coupled with quantitative mass spectrometry techniques such as SILAC to investigate interactions for specific protein targets important in cancer progression.  This project would suit students with molecular cell biology/biochemistry backgrounds.

4. Chemical proteomics

   In collaboration with Dr. F. Liu we have constructed small molecule kinase inhibitor chemical probes to enrich cell samples for particular classes of proteins.  The use of these probes facilitates access to proteins that are often present at low levels and thus not normally detected using standard proteomic techniques. Using mass spectrometry we have investigated how these proteins change in breast cancer cells following stimulation with various signalling ligands. This project would suit students with cell biology/biochemistry backgrounds.

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Selected Publications

1. Sherman, J., McKay, M. J., Ashman, K., Molloy, M. P. How specific is my SRM? The issue of precursor and product ion redundancy. Proteomics, 2009, 9, 1120-1123.
2. Song, X., Bandow, J., Sherman, J., Baker, J. D., Brown, P. T., McDowell, M. T., Molloy, M. P. iTRAQ experimental design for plasma biomarker discovery. J. Proteome Res. 2008, 7 (7), 2952-2958.
3. McKay, M. J., Sherman, J., Laver, M. T., Baker, M. S., Clarke, S. J., Molloy, M. P. The development of multiple reaction monitoring assays for liver derived plasma proteins. Proteomics – Clinical Applications 2007, 1(12), 1570-1581.
4. Saldanha, R. G., Molloy, M. P., Bdeir, K, Cines, D. B., Song, X., Uitto, P. M., Weinreb, P. H., Voilette, S. M., Baker, M. S. Proteomic Identification of Lynchpin Urokinase Plasminogen Activator Receptor Protein Interactions Associated with Epithelial Cancer Malignancy. J. Proteome Res. 2007, 6, 1016-1028.
5. Aristoteli, L. P., Molloy, M. P., Baker M. S. Evaluation of endogenous plasma peptide extraction methods for mass spectrometric biomarker discovery. J. Proteome Res. 2007, 6, 571-581.
6. Molloy, M. P., Donohoe, S., Brzezinski, E. E., Kilby, G. W., Stevenson, T. I., Baker, J. D., Goodlett, D. R., Gage, D. A.  Large-scale evaluation of quantitative reproducibility and proteome coverage using acid cleavable isotope coded affinity tag mass spectrometry for proteomic profiling. Proteomics 2005, 5, 1204-1208.

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