Meet Mingliang (Thomas) Fang, Winner of the 2023 Chemical Research in Toxicology Young Investigator Award

Professor Mingliang (Thomas) Fang is the winner of the 2023 Chemical Research in Toxicology Young Investigator Award, which honors the contributions of an early-career individual who has had a major impact on research in chemical toxicology or a related field. This selection has been made by a committee jointly comprised of members from the Chemical Research in Toxicology Editorial Board and the Executive Committee of the ACS Division of Toxicology. The award will be presented at the 2023 Fall ACS National Meeting in San Francisco, California as part of the TOXI program.

Read the Interview with Dr. Fang

What inspired you to pursue your particular area of research?

Back in 2008, the melamine incident in baby formula inspired me towards the field of chemical analysis and the toxicity of chemical substances. During that incident, melamine was added to dairy products, which caused a huge public health crisis as the development of kidney stone from consuming contaminated products among infants, toddlers, and children. It has taken over half a year to identify melamine as the causal toxicant. This incident has made me realize how important it is to use advanced and fast analytical methods to detect harmful substances in food, drugs, and other consumer products.

When I was a graduate student majoring in environmental chemistry and toxicology (Duke University) and worked as a post-doc in the field of metabolomics (The Scripps Research Institute), I have learned various analytical techniques, especially mass spectrometry, which can be used to detect and quantify various contaminants or endogenous metabolites in complex matrices. Additionally, I have developed a keen interest in the toxicological aspects of chemicals and their impact on human health and the environment.

Those experiences have led me to pursue a career in related fields for more than ten years. I aim to apply my knowledge and skills to solve real-world problems related to chemical safety and risk assessment. I am excited about the prospect of working on innovative analytical techniques that can provide safe and reliable solutions to detect and quantify harmful substances as well as their toxicological mechanism. Among those topics, exposomic research and mixture effect at human or environmentally relevant levels are my top interests. Following transcriptome, proteome, and metabolome, exposome have become a hot topic since its coining in 2005 and been regarded as one useful solution to decipher the real contributions of environmental factors to diseases. However, to date, there are very few successful applications of exposome in practice due to several major challenges such as analytical methods, the integration and interpretation of multi-dimension data (e.g., exposure factors; multi-omics data; diseases; and epidemiological cofounding factors), understanding the biological mechanisms of “external exposure-endogenous change-diseases” (i.e., “Exposure-Biology-Disease”), and the integration of all the associated databases and visualization tools.

What’s next for your research?

In the next few years, I will continue the research on the human exposome and toxicological effects of environmental mixture exposure. In particular, the focus will be on characterizing human exposome using mass spectrometry and deepening the understanding of toxicological effects arising from the emerging and high-risk pollutants, their complex in vivo transformations, and the combined effects of mixtures. The goal is to promote toxicological research based on the concept of “exposome,” exploring the relationship between environmental exposure, disease development, and underlying mechanisms.

The future work will be divided into three aspects. First, I will advance the construction of one integrated exposome platform to expediate the discovery of the “Exposure-Biology-Disease” nexus. Important major functions including statistical learning, exposome database search, mass spectrometry data processing, meta-analysis, biological link via pathway integration and protein-protein interaction and data visualization will be implemented. Second, I would like to further investigate in vivo biotransformation process of the exposome and its implication on chemical toxicity modification, especially in the liver and intestines. Artificial Intelligence (AI) techniques in mass spectrometry data informatics and computational toxicology will be applied to establish effective biotransformation prediction models and provide valuable information for the identification of internal exposure biomarkers as well as their possible toxicity. Finally, I would like to accelerate the screening of chemical protein targets in environmental or biological mixture samples using systems biology and protein-affinity analysis, achieving rapid assessment of “multi-exposure-multi-targets” in the mixtures.

Overall, my future research aims to deepen the understanding of environmentally related disease development and the underlying mechanisms, promoting the development of innovative platforms, predictive models, and experimental approaches to predict and prevent the harmful effects of environmental contaminants.

What do you consider to be the most important advances in your field in the past five years?

During the past five years as an independent PI, I have been committed to research on the methodology of exposome, low-dose mixture exposure and toxicological effects of environmental pollutants. The important advances include: (1) the establishment of several “exposome” analytical platforms, including human exposure and metabolite database (HExpMetDB) (Environ Health Persp, 2021, 129(4):47014), one sensitive stable isotope labeling exposomic platform (CIL-EXPOSOME) (Environ. Sci. Technol. 2019, 49 (16): 10057‐10064), in vivo exposure prediction of human blood exposome using a random forest model in chemical risk prioritization (HExpPredict) (Environ Health Persp, 2023, doi: 10.1289/EHP11305), and the counting-out method to identify the toxicity of each chemical in the mixture (Environ Health Persp, 2020;128(12):127008); (2) the effects of in vivo biotransformation of pollutants and its effect on the toxicity, especially the formation of oligomers in the intestinal tract from biodegradable polymers and the mechanism of their toxic effects (Nat Nanotechnol, 2023, doi: 10.1038/s41565-023-01329-y)；(3) the interaction between chemical and bacteria in modulating host immunity (PNAS, 2021, doi:10.1073/pnas.2011957118/); and (4) the application of multiple omics methods including chemical proteomics, metabolomics, computer-assisted molecular docking, and high-throughput bioassays to screen the possible protein targets of emerging contaminants (Anal. Chem., 2021, 93, 6, 3072–3081；Environ. Sci. Technol. 2020, 54, 15925–15934；Environ. Sci. Technol. 2021, 55, 3, 1842–1851). Those studies contribute to the field of the new framework of exposome and the toxicity of mixture effect.

If you weren’t a chemist working in toxicology, what would you like to be?

If I weren’t a chemist working in toxicology, I would become a mass spectrometry engineer in the environmental or toxicological field. My passion for mass spectrometry based analytical methods has led me to pursue my career in those fields. I am fascinated by the application of advanced analytical techniques such as mass spectrometry in monitoring and assessing the impact of environmental toxicants on human health and ecosystems. I am also highly interested in the development and application of mass spectrometry technology on metabolomics and chemical proteomics. My primary goal is to develop cutting-edge analytical tools that can detect and quantify trace levels of contaminants in complex matrices and identify the endogenous protein-targets of those chemicals.