Liquid chromatography-mass spectrometry system for metabolite-based precision medicine

Metabolites are small biochemicals present in every human cell, tissue and biofluid. These metabolites are essential for life, are primarily involved in metabolism and include sugars and fats which are important for the generation of energy through metabolism of food. Metabolites have other important roles which help us live including the construction of other biochemicals (proteins and DNA), construction of cell walls with fats and the control of chemical processes in the body in response to environmental changes including eating and exercise. The amounts of metabolites in our bodies change in response to environmental changes or in relation to the development and progression of diseases. As examples, the metabolite lactic acid quickly increases in amounts in muscle tissue and blood during exercise and the metabolite glucose increases in blood in the disease diabetes.

In scientific research we study metabolites to understand how we age and how disease processes start and progress. This research can help us understand how diseases develop, help us identify new treatments for diseases and help us diagnose a disease or define the risk of developing a disease early which reduces the level and intensity of treatment and increases the probability of long term survival. The research to be performed will apply the study of thousands of metabolites and this scientific technique is called metabolomics. We will apply a scientific instrument called liquid chromatography-mass spectrometry to allow detection of metabolites based on their weight as different metabolites have different weights (masses). Metabolomics allows the study of thousands of metabolites in discovery research, identification of a small number of important metabolites related to the clinical question and translation in to clinical practice. Metabolites are already used for disease diagnosis including glucose for diagnosis of diabetes. Metabolomics will be applied to study a range of diseases including cancers (lung, blood colorectal), cardiovascular diseases, hormone-driven diseases and women's health/pregnancy disorders.

Importantly, not all humans are the same in how diseases develop and response to different treatments. Traditional medicine treated everyone as if they were the same. A new era of precision medicine is upon us and is an innovative approach to tailoring disease prevention and treatment that takes into account differences in people's genes, environments, and lifestyles. The goal of precision medicine is to target the right treatments to the right patients at the right time. The studies performed will help develop new precision medicine tools for early disease diagnosis or for development of different treatments.

Metabolites are involved in metabolism, in the synthesis of larger biochemicals and cell membranes and in regulatory and signaling pathways. They are important biochemicals which drive many processes important to maintain human health but when these processes are perturbed can lead to the development and progression of human diseases. The study of metabolites in disease onset and progression allows us to understand the pathophysiological mechanisms driving disease development, to identify drugable targets and to identify biomarker panels which can be used for early diagnosis or risk stratification to allow less severe and earlier treatments to be applied which can lead to higher survival rates and lower healthcare costs. In the proposed research we will apply metabolomics in discovery and validation studies using a ultra high performance liquid chromatography-mass spectrometry platform. With this platform we can detect low thousands of metabolites in thousands of samples each year and will apply the platform to a range of clinical diseases including cancers, hormone-related diseases, cardiovascular diseases, women's health, pregnancy disorders and pancreatic exocrine function. These studies will focus on the development of new precision medicine applications which will tailor disease prevention and treatment based on differences in people's genes, environments, and lifestyles. The goal of precision medicine is to target the right treatments to the right patients at the right time.