Bioanalysis Zone

2016 New Investigator: Hua Wang

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hua wangNominee: Hua Wang – WIL Research, A Charles River Company (OH, USA)

Nominated By: Liam Moran – WIL Research, A Charles River Company (OH, USA)

 

 

Supporting Comments: Hua Wang is an outstanding scientist who has contributed significantly to a variety of bioanalysis projects to support drug development programs. These include novel biomarker assays that can simultaneously measure multiple mutational states in patient samples; rapid screening of antibodies for immuno-capture methods with LC/MS detection, high resolution mass spectrometry techniques to discern endogenous/recombinant proteins, quantitative LC/MS assays of peptide-based therapies and high resolution MS assays of gene silencing oligonucleotides. In his role as a scientist in a CRO, he has cracked several problems that biotech/pharma partners have spent years trying to solve.


What made you choose a career in bioanalysis?

During my PhD study, my first bioanalytical experience was to develop a LC–MS/MS method to explore bioactive oxidized lipids in clinical samples. I felt extremely excited when I first saw those molecules appear in mass spectrometer. Since graduating, I have continued my journey in the bioanalytical industry and keep learning new techniques. My work as a research chemist is to develop LC–MS methods for quantitation of both small and large molecules in biological matrices. This is a fun job filled with challenges and new techniques so I will never feel bored. And it is also an honorable career in improving human health.

Describe the main highlights of your bioanalytical research, and its importance to the bioanalytical community.

My work at WIL Research, a Charles River Company is mainly focused on developing LC–MS methods for protein based drugs and biomarker bioanalysis. One study I would like to highlight is the development of a novel LC–MS assay to allow fast identification and quantification of various genetic mutants of transthyretin, a protein biomarker in ATTR disease. In this method, we are the first to combine MSIA technology and LC–HRAM MS to achieve a high-throughput and reliable intact TTR protein analysis. This method has been successfully applied in clinical sample analysis to support a clinical trial study. And the results will be presented at AAPS National Biotechnology Conference (Boston, MA, USA, 16–18 May 2016). Besides, I have several publications related to analysis of oxidized lipids in blood. One of my publications described the LC–MS/MS detection of novel phosphatidylethanolamine derivatives in human plasma and discovered these molecules can be potential biomarkers for age-related macular degeneration disease. This paper was featured as a cover paper by Chemical Research in Toxicology in 2014. This reported method was then applied to a hyperlipidemic mice model study and the results were published in the journal Blood in 2016.

What is the impact of your work beyond your home laboratory?

I have published more than 15 publications in scientific journals and conferences, which have attracted 90 citations to my work by scientists in more than 15 countries.

Describe the most difficult challenge you have encountered in the laboratory and how you overcame it.

Reactive aldehydes generated from lipids oxidation can modify primary amine groups of ethanolamine phospholipids (EP) at cell membranes. These reactive aldehydes modified phosphatidylethanolamine derivatives in blood are extremely difficult to be seen by LC–MS because there are dozens of different EPs in biological systems. Considering the low levels of these molecules and the difficulty in synthesizing every authentic standard, it is challenging to develop a single LC–MS method to quantify EP modification by a certain aldehyde.

In my study to detect carboxyethylpyrrole (CEP) modified EPs in human plasma, in order to overcome this problem, I used Phospholipase D from S. chromofuscus to selectively release the ethanolamine moiety from the polar heads of all types of ethanolamine phospholipids. A heavy isotope labeled CEP-EP molecule was chemically synthesized and spiked as an internal standard to compensate the variability of enzyme activity. This method not only helps to eliminate the diversity inherent in naturally occurring EPs by converting all of different CEP modified EPs into a single molecule, CEP-ethanolamine, but also helps to enhance the detection limit by amplifying the level of analyte (this research was published in Chemical Research in Toxicology in 2014.

Describe your role in bioanalytical communities/groups.

I am a member of American Association of Pharmaceutical Scientists.

Please list up to five of your publications in the field of bioanalysis:
  1. Wang H, Myers NR, Nelson P et al. Development and qualification of a mass spectrometric immunoassay for identification and quantification of wild-type and mutant transthyretin in human serum. Presented at: American Association of Pharmaceutical Scientists, National Biotechnology Conference. Boston, MA, USA, 16–18 May 2016.
  2. Biswas S, Xin L, Panigrahi S et al. Novel phosphatidylethanolamine derivatives accumulate in circulation in hyperlipidemic ApoE-/- mice and activate platelets via TLR2. Blood (2016) (In press).
  3. Wang H, Guo J, West X et al. Detection and biological activities of carboxyethylpyrrole ethanolamine Phospholipids: a correlation with age-related macular degeneration. Chem. Res. Toxicol. 27(12), 2015–2022 (2014).
  4. Wang H, Linetsky MD, Guo J et al. 4-Hydroxy-7-oxo-5-heptenoic acid (HOHA) lactone is a biologically active precursor for the generation of 2-(ω-carboxyethyl)pyrrole (CEP) derivatives of proteins and ethanolamine phospholipids. Chem. Res. Toxicol. 28(5), 967–977 (2015).
  5. Harris SS, Zhang GF, Sadhukhan S et al. Metabolomics and mass isotopomer analysis as a strategy for pathway discovery: pyrrolyl and cyclopentenyl derivatives of the pro-drug of abuse, levulinate. Chem. Res. Toxicol. 26(2), 213–220 (2013).
Please select one publication from above that best highlights your career to date in the field of bioanalysis and provide an explanation for your choice.
  1. Wang H, Myers NR, Nelson P et al. Development and qualification of a mass spectrometric immunoassay for identification and quantification of wild-type and mutant transthyretin in human serum. Presented at: American Association of Pharmaceutical Scientists, National Biotechnology Conference. Boston, MA, USA, 16–18 May 2016.

Protein biomarker bioanalysis by LC–MS is an attractive field for bioanalysis. Although many LC–MS methods for protein biomarkers quantitation use the bottom-up approach of monitoring tryptic peptides, intact protein analysis by high resolution and accurate (HRAM) MS can be a powerful tool to identify the genetic mutants of protein biomarkers in rare diseases. In this publication we developed a method that not only allows a high-throughput, automated approach for specific immunoaffinity enrichment of transthyretin from human serum, but also enables fast and reliable identification and quantitation of the transthyretin mutants with only trace mass differences.

Find out more about this year’s New Investigator Award, the prize, the judging panel and the rest of our nominees.

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