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Research

Research Summary

Over 100,000 chemicals have been registered for production and use worldwide. Assessment of the toxicities of such a immense number of contaminants is infeasible for conventional 'bottom-up' strategies. In our group, we propose a 'top-down' toxicity testing strategy by characterizing the physical contaminant-protein interactions on a global level. We aim to dissect the billions of chemical-protein interactions derived from >100,000 chemical contaminants and >20,000 human proteins by focusing on two major research directions: 1) We aim to develop bioanalytical methods to identify chemical contaminants binding to key proteins from the ‘chemical cocktails’ of environmental mixtures. 2) We aim to employ chemical proteomics methods to identify the physical protein targets of emerging chemical contaminants on the proteome-wide level. Eventually, we aim to complete all 7 billion interactions between 350,000 chemicals and 20,000 human proteins, termed as environmental Chemical-Protein Interaction Network (eCPIN). All newly discovered interactions will be deposited in an online database (https://penggroup.shinyapps.io/ecpin/) which is freely accessible.

 

Nontargeted Identification of Unknown Contaminants

The majority of chemicals in the environment remain unidentified, which is the very first challenge we aim to address to more completely understand the toxicities of environmental mixtures. We aim to develop analytical methods with High-Resolution Mass Spectrometry (HRMS), as well as computational algorithms to detect hundreds of contaminants in a single run.   

 

Identification of Protein Targets with Chemical Proteomics

The majority of contaminants exert toxicities by attacking proteins. However, identification of protein targets is extemely challenging due to the huge number of proteins (~20,000 in humans) and dynamic range (>105 copies). We aim to develop different chemistry toolboxes (i.e., thermal stability, photoreactive probes) integrated with quantitative proteomics to identify protein targets of bioactive chemicals.  The toolboxes are currently applied to a broad class of chemicals including atmospheric pollutants, disinfection by-products, organophosphate flame retardants, per- and polyfluoroalkyl substances and natural products.    

 

Identification of Bioactive Chemicals Binding to Key Proteins from Environmental 'Chemical Cocktails'

As mentioned above, toxicity testing of each individual compound by conventional 'bottom-up' strategy is infeasible. We aim to develop analytical chemistry and biochemistry toolboxes for high-throughput characterization of bioactive chemicals from the 'chemical cocktails' of environmental mixtures. We have developed affinity pull-down methods by using biomolecules to direclty isolate bioactive chemicals from the environmental extracts consisting of millions of chemicals.