Anuri Shah is currently pursuing a fully funded Joint Ph.D. between The University of Hong Kong and King’s College London. Her doctoral thesis is aimed at understanding pathways involved in Parkinson’s disease and subsequently studying the protective effects of herbal medicine. Her expertise lies in cellular and animal models, coupled with molecular biology and metabolomics. She has a Masters in Pharmacology from the University of Southern California, where she also studied protein chemistry in the context of Parkinson’s disease.
Parkinson’s disease (PD) is a debilitating neurodegenerative disorder, with no cure at present. An in-depth understanding of the pathology of PD will pave ways for effective treatment options. In recent years metabolomics has emerged as a powerful tool to identify biomarkers and mechanisms for a range of diseases. The aim of this study was to use systems metabolomics to identify changes in an in-vivo model of PD. Male Sprague- Dawley rats were injected with the toxin 6-hydroxydopamine (6-OHDA) into the mid-brain, to induce Parkinsonism. Animals injected with saline were used as the control group. Two weeks after the injection, behaviour tests were carried out to assess motor dysfunction, followed by plasma and brain collection for untargeted metabolic profiling. Palmitic acid (p = 1.76 x 10-2, q = 3.72 x 10-2, FC = 1.81) and stearic acid (p = 2.56 x 10-2, q = 3.84 x 10-2, FC = 2.15) were significantly upregulated in the plasma of the PD group, while mono-palmitin (p = 2.4 x 10-2, q = 4.8 x 10-2, FC = -11.7), mono-stearin (p = 3.1 x 10-2, q = 3.72 x 10-2, FC = -15.1) and myo-inositol (p = 3.81 x 10-2, q = 3.81 x 10-2, FC = -3.32) showed a significant imbalance in their mid-brains. Receiver operating characteristic (ROC) curves showed that all these metabolites had an area under the curve (AUC) of > 0.8, which indicates good prediction ability. Furthermore, the plasma metabolites were significantly correlated with the behaviour test scores. These results show that plasma saturated free fatty acids and their mono-glycerides in the brain were associated with 6-OHDA induced toxicity. All these metabolites showed a good prediction ability. The plasma fatty acids also had a strong correlation with motor dysfunction, an integral symptoms of PD, suggestive of their potential as biomarkers.
Ya-Ju Hsieh has her expertise in mass spectrometry of metabolomics and proteomics analysis. Her study is major in using quantitative metabolomics profiling approaches to investigate urine samples of cardio surgery patients with or without cardioplegia treatment. The platform was developed by Prof. Liang Li from University of Alberta, Canada, which is based on modified metabolites with dansyl group which can efficiently improve the ionization efficiency of metabolites for 1~3 orders. Using this method, we detected more than 14,000 metabolites from 100 samples which provides systemic analysis of metabolomicsalteration. This method was focused on metabolites with amine and phenol functional groups, and the platform to label alcohol, aldehyde and acid are still working on.
The discovery of Bretschneider’s histidine-tryptophan-ketoglutarate (HTK) cardioplegia solution had been one of major advancement in cardiac surgery to offer myocardial protection. However, metabolic alteration of these additive in the whole body has not been systematically investigated. Using non-targeted mass spectrometry-based method, the deep urinary metabolome may provide a systemic view of metabolic shifts in patients receiving HTK. Prospective urine samples were collected from 100 patients underwent cardiac surgery and the metabolomic changes were profiled by a high-performance chemical isotope labeling liquid chromatography (LC-MS) method. Over 14642 metabolites were quantified using differential 13C-/12C-dansyl labeling LC-MS, which targeting the amine/phenol submetabolome from the urine specimens. We identified 285 significantly differential metabolites (fold change more than 5) and assembled several potential metabolic pathway map derived from dysregulated metabolite hits. Our data indicated an up-expressed histidine metabolism with subsequent increased glutamine/glutamate metabolism, altered purine and pyrimidine metabolism, and up-expressed vitamin B6 metabolism in patients receiving HTK. Such information provides solid evidence outlining the shift in metabolic pathways and establishes a basis for further study regarding the key mechanisms of HTK solution in organ protection or potential harm.