Bioanalysis Zone

2013 Young Investigator Award Nominee: Jeanethe Anguizola

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Jeanethe Anguizola YIA

 

Nominee: Jeanethe Anguizola, University of Nebraska, USA

Nominated By: David S. Hage, University of Nebraska, USA

 

Supporting Comments: As a researcher, Jeanethe has proven to be enthusiastic, diligent and hard working. Much of her research has involved studies of the changes in binding of sulfonylurea drugs to proteins that have been modified with glucose during diabetes. In these studies, she has developed methods using affinity microcolumns and HPLC to obtain binding isotherms for these interactions and has determined both the number of binding sites and binding constants for several drugs with normal and modified proteins, such as may be produced in diabetes. She has not only created methods for isolating and using modified proteins from individual patient samples, but she has demonstrated how affinity microcolumns containing these proteins can be used in biointeraction studies. This research is important in that it demonstrates how HPLC-based affinity columns can be used as synthetic models for drug–protein binding in the circulatory system and shows the possibility of using such columns as tools in personalized medicine. Jeanethe currently has seven published papers, one published book chapter and two submitted papers based on this research. She has a bright future in the area of bioanalysis and I have high expectations for her continued future work in this field.


What drove you to choose a career in bioanalysis?

Among all the fascinating and exciting areas in chemistry, I have been drawn to the bioanalysis of pharmaceutical agents within the body since my early years as an analytical chemist. In particular, I have been interested in the use and development of new analytical techniques to understand the effects of disease states on biological interactions, such as the binding of drugs to serum proteins. This curiosity is what has motivated me to develop methods for personalized medicine to study drug–protein interactions, as could be of interest for predicting the behavior of pharmaceuticals in humans or for screening possible drug candidates.

Describe the main highlights of your bioanalytical research, and its importance to the bioanalytical community both now and in the future.

My research has focused on the development of affinity microcolumns for use in HPLC as a new bioanalytical approach for personalized medicine and for examining the effects of diseases, such as diabetes on biological interactions. For instance, the high levels of blood glucose in diabetics is known to increase the non-enzymatic glycation of proteins such as human serum albumin (HSA), which is an important transport protein for many drugs. My research has been examining how the extent of glycation for HSA will affect the binding of various drugs with this protein. I first carried out this research with in vitro glycated HSA and sulfonylurea drugs that are used to treat type II diabetes. I have recently combined this approach with the immunoextraction of in vivo glycated HSA to create affinity microcolumns that can be made from only 20 µL of serum from individual diabetic patients. With these affinity microcolumns, I have been able to obtain a better understanding of how glycation can affect drug–protein interactions in diabetes. This bioanalytical approach is not limited to glycated HSA but could be adapted to other modified proteins and disease states of interest to the bioanalytical community and in personalized medicine.

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

One challenge I faced in my research was learning how to properly handle, process and use clinical samples. First, I needed to learn to work with clinical specimens, making sure that all the necessary precautions were taken into consideration for materials that may contain blood-borne pathogens. Also, the amount of clinical samples available was limited so I needed to design an approach that would require only a small volume of serum. In addition, it was desirable for the isolation method I would develop to not change the activity of the captured protein (HSA) and to provide a high recovery of this protein from serum. These are the reasons why I decided to create an immunoaffinity method that took advantage of a high-specificity antibody resin to bind HSA in serum. This method proved to be a fast and reliable approach for the isolation of glycated HSA from the serum of diabetic patients, which, in turn, allowed me to prepare individualized microcolumns for biointeraction studies. I can envision a future where this approach could be used to help design personalized treatment regimes for diabetic patients. This work also illustrates how a range of bioanalytical methods can be combined to address difficult problems.

Where do you see your career in bioanalysis taking you?

I see myself using the knowledge and the experience that I have acquired in the development of new analytical applications that allow a better understanding of the complex biological interactions that are present within the body. I am very interested to continue working with personalized approaches and in using a combination of bioanalytical techniques to provide a more complete perspective on the effects of different diseases on biological interactions. In addition, I would like to work in the miniaturization of analytical platforms that would allow high-throughput analysis and the development of handheld devices to provide faster diagnosis and more effective treatments. I would also like to work in the automation of bioanalytical assays to increase the productivity and reliability of results. It has been a life-long dream of mine to help others to achieve the same degree of education that I was so fortunate to obtain by studying in the USA. I envision myself working in scientific collaboration with Latin American researchers and professors, and, in that way, have the opportunity to encourage young scientists and students from these institutions to work in bioanalytical research.

How do you envisage the field of bioanalysis evolving in the future?

I truly believe that the field of bioanalysis will continue to expand and grow in the future. A great part of this growth will be due to the development and optimization of a large number of new and improved analytical techniques. I think these technological improvements will make it possible to achieve more research than ever before due to the use of small amounts of samples and faster analysis times that will be possible, as well as the miniaturization of analytical platforms and automation of bioanalytical methods. I also envision in the future an increase in the number of scientific collaborations, not only between chemists but also between interdisciplinary experts in fields such as biology, biochemistry, bioinformatics and medicine. In the future, hopefully, new bioanalytical assays will transition faster and more smoothly to a clinical setting, where they can be used to provide a faster diagnosis and more effective treatments.

Please list 5 of your recent publications, and select one that best highlights your career to date in the field of bioanalysis.

Anguizola J, Joseph KS, Matsuda R, Clarke W. Development of affinity microcolumns for drug-protein binding studies in personalized medicine: Interactions of sulfonylurea drugs with in vivo glycated human serum albumin. Anal. Chem. (submitted) (2013).

Matsuda R, Anguizola J, Joseph KS, Hage DS. Analysis of drug interactions with modified proteins by high-performance affinity chromatography: Binding of glibenclamide to normal and glycated human serum albumin. J. Chromatogr. A 1265, 114–122 (2012).

Hage DS, Anguizola JA, Jackson AJ et al. Chromatographic analysis of drug interactions in the serum proteome, Anal. Methods 3, 1449–1460 (2011).

Joseph KS, Anguizola J, Hage DS. Binding of tolbutamide to glycated human serum albumin. J. Pharm. Biomed. Anal. 54, 426–432 (2011).

Joseph KS, Anguizola J, Hage DS. Chromatographic analysis of acetohexamide binding to glycated human serum albumin. J. Chromatogr. B 878, 2775–2781 (2010).

First choice: Matsuda R, Anguizola J, Joseph KS, Hage DS. Analysis of drug interactions with modified proteins by high-performance affinity chromatography: Binding of glibenclamide to normal and glycated human serum albumin. J. Chromatogr. A 1265, 114–122 (2012).

Reasoning: This paper describes how HPLC-based affinity columns can be used for studying both global and site-specific interactions between non-polar drugs and in vitro glycated HSA. This work has since been expanded in my paper that has been submitted to Anal. Chem., in which this approach has been used to directly study drug interactions with in vivo glycated HSA from clinical samples.

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