Reid laboratory: Proteomics and lipidomics in health and disease
Our research focuses on the development and application of quantitative proteome and lipidome analysis strategies to identify and characterize functional biomarkers of disease, and for mass spectrometry based clinical diagnostics.
A broad variety of analytical biochemistry techniques are employed, including novel sample extraction, chemical derivatization, gas-phase separation and ultra-high resolution tandem mass spectrometry (MS/MS), to comprehensively identify and quantify changes in protein expression and post translational modifications, or complex lipid abundances, that are associated with the dysregulation of normal cellular function.
Ultimately, the results obtained from these studies can provide critical insights toward improving our understanding of the onset and progression of disease pathogenesis, including in cancer, diabetes and diabetic complications, and may enable the identification of candidate biomarkers for improved disease diagnostic or prognostic monitoring, or novel targets for therapeutic intervention.
Figure 1: Ultra-high resolution mass spectra of crude lipid extracts from primary human colon carcinoma cell line SW480, and its lymph node metastatic derivative SW620. From these spectra, >1000 lipids can be identified, and relative quantification performed between the cell lines, with significant changes in both plamanyl- and plasmenyl-ether lipid abundances. siRNA knockdown of the rate limiting peroxisomal enzyme for ether lipid biosynthesis, alkylglyceronephosphate synthase (AGPS), within the SW620 cells followed by comprehensive lipidome profiling and PCR array analysis, results in the attenuation of multiple genes known to be associated with molecular and phenotypic characteristics of cancer malignancy and metastasis.
Dr Eileen Ryan, Research Fellow
Dr Troy Attard, Research Fellow
Mr Shuai Nie, PhD, visiting from Michigan State University
Mr Xinghe Zhang, MSc
Mr Yepy Rustam, MSc Biotechnol
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- Lydic TA, Townsend S, Adda CG, Collins C, Mathivanan S, Reid GE. Rapid and Comprehensive 'Shotgun' Lipidome Profiling of Colorectal Cancer Cell Derived Exosomes. Methods 2015; In Press. doi: 10.1016/j.ymeth.2015.04.014.
- Zhou X, Mester C, Stemmer PM, Reid GE. Oxidation Induced Conformational Changes in Calcineurin Determined by Covalent Labelling and Tandem Mass Spectrometry. Biochemistry 2014; 53: 6754-6765. PMID: 25286016.
- Lydic TA, Busik JV, Reid GE. A Monophasic Extraction Strategy for the Simultaneous Lipidome Analysis of Polar and Nonpolar Retina Lipids. J Lipid Res 2014; 55: 1797-1809. PMID: 24879804.
- Bennett LD, Brush RS, Chen M, Lydic TA, Reese K, Reid GE, Busik JV, Elliott MH, RE. Effect of reduced retinal VLC-PUFA on rod and cone photoreceptors. Invest Ophthalmol Vis Sci. 2014; 55: 3150-3157. PMID: 24722693.
- Chen W, Zhou H, Liu S, Fhaner CJ, Gross BC, Lydic TA, Reid GE. Altered lipid metabolism in residual white adipose tissues of Bscl2 deficient mice. PLOS One 2013; 8: e82526.
- Teague H, Fhaner CJ, Harris M, Duriancik DM, Reid GE, Shaikh SR. N-3 PUFAs enhance the frequency of murine B cell phenotypes and restore the impairment of antibody production to a T-independent antigen in obesity. J Lipid Res 2013; 54: 3130-3138. PMID: 23986558.
- Sanjaya R, Miller R, Durrett TP, Kosma DK, Lydic TA, Muthan B, Koo AJK, Bukhman YV, Reid GE, Howe GA, Ohlrogge J, Benning C. Altered Lipid Composition and Enhanced Nutritional Value of Arabidopsis Leaves Following Introduction of an Algal Diacylglycerol Acyltransferase 2. Plant Cell 2013; 25: 677-693. PMID: 23417035.
- Fhaner CJ, Liu S, Ji H, Simpson RJ, Reid GE. Comprehensive Lipidome Profiling of Primary and Metastatic Colon Adenocarcinoma Cell Lines. Anal Chem 2012; 84: 8917-8926. PMID: 23039336.
- Tan Y-J, Wang W-H, Zheng Y, Dong J, Stefano G, Brandizzi F, Garavito RM, Reid GE, Bruening ML. Limited Proteolysis via msec-Digestions in Protease-Modified Membranes. Anal Chem 2012; 84: 8357-8363. PMID: 22950601.
- Opreanu M, Tikhonenko M, Bozack S, Lydic TA, Reid GE, McSorley KM, Sochacki A, Perez GI, Esselman WJ, Kolesnick R, Grant MB, Busik JV. The unconventional role of acid sphingomyelinase in regulation of retinal microangiopathy in diabetic human and animal models. Diabetes 2011; 60: 2370-2378. PMID: 21771974.
- Zhang X, Hiser C, Tamot B, Benning C, Reid GE, Ferguson-Miller SM. Combined Genetic and Metabolic Manipulation of Lipids in Rhodobacter sphaeroides Reveals Non-phospholipid Substitutions in Fully Active Cytochrome c Oxidase. Biochemistry 2011; 50: 3891-3902. PMID: 21476580.
- Lydic TA, Renis R, Busik JV, Reid GE. Analysis of Retina and Erythrocyte Glycerophospholipid Alterations in a Rat Model of Type 1 Diabetes. JALA 2009; 14: 383-399. PMID: 20161420.
- Meyer JA, Subasinghe W, Sima AFA, Keltner Z, Reid GE, Daleke D, Spence DM. Zinc-activated C-peptide Resistance to the Type 2 Diabetic Erythrocyte is Associated with Hyperglycemia-induced Phosphatidylserine Externalization and Reversed by Metformin. Mol Biosystems 2009; 5: 1157-1162. PMID: 19756305.
- A mass spectrometry assay for quantitative analysis of P. falciparum Histidine Rich Protein 2
- Comprehensive lipidome profiling to identify functional biomarkers of colorectal cancer metastasis
- Lipidome profiling of inflammatory biomarkers for beta cell autoimmunity in type 1 diabetes
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