2015 Young Investigator finalist: Xiwei Zheng
Nominee:
Nominated By:
Supporting Comments:
What made you choose a career in bioanalysis?
The study of biological interactions, such as those that occur in the circulation, can provide important information on the activity and metabolism of drugs and other agents within the body. The need to better understand these interactions has ignited my enthusiasm to be a bioanalytical chemist. Throughout my graduate studies I have been interested in developing new methods to study biological interactions and to characterize binding parameters in an efficient manner. A career in bioanalysis has provided me with many opportunities to learn and create new techniques for this work, which in the future could be employed in various clinical and pharmaceutical applications.
Describe the main highlights of your bioanalytical research, and its importance to the bioanalytical community.
My research has involved studying the interaction of drugs/hormones with serum proteins using high-performance affinity chromatography (HPAC). The reversible interactions of many drugs and hormones with these proteins results in a portion of these solutes being present in a free form, which usually represents the biologically-active form. The rate constants and binding constants for these systems are both of interest in helping us to better understand these interactions within the body. In my research, a new HPAC method has been created to simultaneously determine both the equilibrium constants and rate constants for this type of interaction. By using HPAC in a multi-dimensional system this method was also adapted to measure the free fraction of drugs in samples such as human serum. The techniques developed in my research are label-free and have short analysis times (i.e., minutes), needing only microliter amounts of a sample. In related work I developed a new immobilization method for making HPAC columns, which gives up to a 2-fold increase in protein content when compared with traditionally prepared supports. This immobilization scheme has been used to make HPAC microcolumns for drug-protein binding studies and enhanced binding capacities and activities for various applications involving protein-based columns.
Describe the most difficult challenge you have encountered in the laboratory and how you overcame it.
One of my projects was to develop a method to increase the binding capacity and activity of immobilized proteins by combining a traditional covalent immobilization method with protein cross-linking. This project was difficult for me because it was quite different from other projects on which I had worked, and I had to consider many factors for the immobilization and modification processes. I also had to do an extensive search of the literature to find possible strategies that I could use. Sometimes the results I obtained with these strategies were quite different from what I expected. To find the reasons for these differences, I discussed my results with colleagues in the areas of organic chemistry, biological chemistry and physical chemistry. In the end, I successfully developed a hybrid immobilization method that produced about a two-fold increase in total protein content and activity over traditional methods. This experience not only made me learn something new, but it showed me the power of research and that I can take on a new area and solve a challenging problem as long as I continue to learn.
Where do you see your career in bioanalysis taking you?
Throughout my graduate studies I was able to learn about and use various analytical techniques, especially HPAC, to study biological interactions and measure drugs and hormones in biologically relevant samples. These projects instilled in me a great interest in method development. They also gifted me with an interest in the use of new approaches to examine biological interactions and to study various pharmaceutical agents. To expand my experience in this field and in bioanalysis, I plan to keep learning and obtaining experience using other analytical methods, such as MS and capillary electrophoresis. By merging my knowledge in these current and new fields, it will be possible for me to continue to develop novel approaches for bioanalysis and biological interaction studies. In addition, I see my career leading me to work and co-operate with experts from many other areas. Through sharing and discussing our knowledge and experience with each other, new ideas and sources of inspiration should appear that will lead to further improvements in modern bioanalysis. I plan to work as a postdoctoral researcher after my graduation to expand my current knowledge. I hope to eventually become a scientist in industry and use my knowledge to improve our daily lives.
How do you envisage the field of bioanalysis evolving in the future?
I think the bioanalysis of smaller sample volumes with continue to improve, with one of these improvements being shorter analysis times. I also expect increases in sensitivity and selectivity to continue for the analysis of trace targets in clinical samples. For these developments to occur, people working within the field of bioanalysis will need to create new analytical techniques and materials for processing and handling biological samples such as serum, tissues, and urine. I also see a need for collaboration from various fields to achieve these goals. This would include researchers from the fields of biology, biochemistry, analytical chemistry, medicine, organic chemistry and electronic engineering to provide new ideas about possible materials and platforms for bioanalysis. Scientists who are trained in this collaborative environment would be expected to not only have strong knowledge of various techniques and methods, but also be able to break through the current limits that exist within these separate areas. I believe through these efforts that bioanalysis will undergo dramatic development and continue to be an important field in providing information allowing us to better understand the various processes that occur in biological systems.
Please list up to five of your publications in the field of bioanalysis:
1. Zheng X, Bi C, Li Z, Podariu M, Hage DS. Analytical methods for kinetic studies of biological interactions: A review. J. Pharm. Biomed. Anal. doi:10.1016/j.jpba.2015.01.042 (2015) (Epub ahead of print).
2. Zheng X, Matsuda R, Hage DS. Analysis of free drug fractions by ultrafast affinity extraction: interactions of sulfonylurea drugs with normal or glycated human serum albumin. J. Chromatogr. A 1371 (2014) 82—89.
3. Zheng X, Li Z, Podariu M, Hage DS. Determination of rate constants and equilibrium constants for solution-phase drug-protein interactions by ultrafast affinity chromatography. Anal. Chem. 86, 6454—6460 (2014).
4. Zheng X, Li Z, Hage DS. Analysis of biomolecular interactions using affinity microcolumns: a review. J. Chromatogr. B 968, 49—63 (2014).
5. Zheng X, Yoo MJ, Hage DS. Analysis of free fractions for chiral drugs using ultrafast extraction and multi-dimensional high-performance affinity chromatography. Analyst 138, 6262—6265 (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.
Zheng X, Li Z, Podariu M, Hage DS. Determination of rate constants and equilibrium constants for solution-phase drug-protein interactions by ultrafast affinity chromatography. Anal. Chem. 86, 6454—6460 (2014).
In this project, I developed a new method based on ultrafast affinity extraction and affinity microcolumns to rapidly characterize both the equilibrium constants and rate constants for drug-protein interactions in solution. This was a label-free analysis method that required small amounts of sample (1 μL) and had analysis times of only a few minutes while providing agreement with reference methods. This was a general method that could be used with various drugs and proteins for applications such as the screening of drug candidates and rapid biointeraction studies, as well as in studying interactions between proteins and other solutes (e.g., hormones).
Join us for our webinar with Emmi on 12 January 2016, during which Emmi will cover her work in-depth. To register for the webinar, click here.
