Research Program Overview
Dietary, environmental, and lifestyle factors have large impacts on human health and therapeutic response. To better understand the dynamic metabolic interactions between nutritional status, drugs that target metabolism, and etiology of disease, the Liu lab is dedicated to the development and application of new metabolomics methods in biomedical research. Our research program has two major research areas.
First, we seek to quantitatively understand the nutritional and metabolic regulation of cancer cell responses to targeted therapies. The goal of this is to foster effective and targeted therapy development, such as the rational combination of multiple inhibitors or dietary interventions. For example, metformin, a biguanide, is a commonly prescribed agent for the management of type II diabetes that also shows promise in reducing the incidence of cancers. Previously, we identified that low glucose levels and high levels of reactive oxygen species enhance the efficacy of metformin in ovarian cancer. We are actively exploiting this discovery by testing additional factors such as serum vitamin levels and lipid profiles, to improve both the precision therapy targeting of metformin and the basic understanding of cancer biology driving this patient stratification.
Second, we investigate the associations of endogenous metabolic toxins with modifiable diet and lifestyles and examine the mechanisms of action of these factors in altering human health. This provides critical insight at the molecular level of how an individual’s lifestyle and nutritional status affect their health, providing a way to measure the internalized interaction with the wider environment in the context of a unique individual phenotype. Recently, we observed metabolic imbalances lead to the release of endogenous aldehyde toxins in cells and animals. Currently, we are quantitively determining these metabolic toxins in animals on different diet regimens and further characterizing the cellular damage caused by these toxins.
To conduct these projects, we have developed a high-resolution mass spectrometry-based metabolomics workflow which enables us to simultaneously quantify hundreds of metabolites and lipids from various types of samples on a daily basis. In addition to metabolomics, we also routinely employ biochemistry, cellular and molecular biology tools, mouse models, and bioinformatics approaches to comprehensively explore biological questions. This provides a complete translational pipeline, from in silico, cell, animal, and to human studies. As a necessary part of this translational effort, the projects in our group represent extensive collaborative efforts among knowledgeable individuals with diverse skill sets.
B.S. Chemistry University of Science and Technology of China 2007
Ph.D. Chemistry University of Pennsylvania 2012
Post-Doctoral Pharmacology and Cancer Biology Duke University