Date/Time
Date(s) - 06/08/2020
10:00 am - 11:00 am

Title: MULTISEGMENT INJECTION-NONAQUEOUS CAPILLARY ELECTROPHORESIS-MASS

 SPECTROMETRYBASED METABOLOMICS FOR RAPID ANALYSIS OF FATTY ACIDS         FOR  DIETARYAND CARDIOMETABOLIC RISK ASSESSMENT 

Date:                     Thursday, August 6, 2020

Time:                    10:00a.m.  

Zoom:                   contact fehert@mcmaster.ca

 Host:                    Dr. PhilipBritz-McKibbin 

 Abstract:

 Biomarkers play a key role in human healthfor early disease screening for public health, improved diagnosis of humandiseases, and monitoring of treatment responses on an individual level.However, there is urgent need for high throughput technologies to acceleratebiomarker discovery based on comprehensive analyses of metabolites and lipidsin complex human biofluids. This thesis contributes to new advances inmetabolomics research and biomarker discovery in three major areas. Inspecific, this thesis describes (1) the development and validation of amultiplexed separation platform based on multisegment injection-nonaqueouscapillary electrophoresis-mass spectrometry (MSI-NACE-MS) for the rapid andaccurate determination of fatty acids and synthetic environmental lipids inblood specimens, (2) the application of this technique in support ofnutritional epidemiology for objective assessment of dietary fat intake inwomen that can be correlated with self-reported food frequency questionnaires,and (3) the discovery of a panel of serum biomarkers for differentiation ofperipheral artery disease (PAD) in older persons at high risk for limbamputation and death. Chapter I provides an introduction in biomarkersand metabolomics, including an overview of the data workflow when performingcomprehensive metabolite profiling with emphasis on methods applicable tocomprehensive fatty acid analysis. Chapter II introduces a novel assaybased on MSI-NACE-MS for high throughput analyses of nonesterified or totalhydrolyzed fatty acids in serum/plasma extracts following a rigorous methodoptimization and an inter-method comparison to conventional gas chromatography(GC) to demonstrate good mutual agreement. MSI-NACE-MS enables multiplexedanalyses of seven samples within a single run with stringent quality control,robust inter-batch correction, and accurate electromigration modeling for lipididentification without pre-column chemical derivatization and complicatedsample workup procedures. Chapter III further expands concentrationsensitivity when using MSI-NACE-MS/MS for rapid biomonitoring of low nanomolarlevels of perfluoroalkyl substance (PFASs) exposures as they are a class ofubiquitous environmental pollutants with endocrine-disruption functions.Perfluorooctanoic acid and perfluorooctanesulfonic acid were quantified in asubset of serum extracts from pregnant women before and after 2009 with lowerexposures measured in accordance with enforced PFAS regulation. Chapter IVdemonstrates the clinical utility of circulating NEFA for accurate nutritionalassessment of fat intake in women. MSI-NACE-MS was applied in observational andintervention studies to demonstrate that polyunsaturated omega-3 and saturatedodd-chain NEFAs serve as promising dietary biomarkers to monitor intake of oilyfish/fish oil supplement and full-fat dairy intake, respectively. Chapter V describesan untargeted characterization of the serum metabolome of nondiabetic PADpatients for differentiation of chronic limb-threatening ischemia fromintermittent claudication as compared to the ankle brachial index. A panel ofserum metabolites, including several amino acids and fatty acids were identifiedas promising clinical biomarkers for early diagnosis and/or prognostication ofPAD that also provides insights into its underlying pathophysiology. Lastly, ChapterVI provides an overview of the major contributions derived from thisthesis, as well as a perspective on future research initiatives.