2015 Young Investigator: Ryan Matsuda
Nominee:
Nominated By:
Supporting Comments:
What made you choose a career in bioanalysis?
During my undergraduate studies, I had the opportunity to conduct research in physical and analytical chemistry, while also being enrolled on a biochemistry curriculum. My undergraduate experience guided me into pursuing graduate research in the area of bioanalysis, where I wanted to apply my knowledge to explore metabolic diseases such as diabetes. Through my graduate studies in bioanalysis I have been able to develop and utilize new tools and techniques that could be used to examine the effect of diabetes on both the structure and function of serum proteins and to consider the implications of this work in personalized medicine.
Describe the main highlights of your bioanalytical research, and its importance to the bioanalytical community.
Most of my doctorate research has involved the development and utilization of new tools based on HPAC and MS to examine the effects on diabetes on the structure and function of glycated HSA. Diabetes can lead to the non-enzymatic glycation of HSA, resulting in changes to drug interactions with this protein. I have used HPAC to examine the binding of several sulfonylurea drugs with HSA that contained various levels of in vitro glycation. These studies indicated that glycation can affect the binding of sulfonylurea drugs to this protein and that these changes vary from one drug to next. This information could be used to improve the use of these drugs in the treatment of type II diabetes (e.g., in personalized medicine) and illustrate how complex drug-protein interactions can be examined by HPAC for pharmaceutical research. My research has also involved the use of multidimensional MS to compare the structures of normal and glycated HSA. This work has made it possible to locate and identify glycated-related modifications on HSA, as can be compared with my functional studies to determine how the presence of these modifications affects the interactions of drugs with HSA.
Describe the most difficult challenge you have encountered in the laboratory and how you overcame it.
A major advantage of HPAC for examining drug-protein interactions is its ability to provide detailed information on the equilibrium constants and number of binding sites for these interactions. However, this technique does require that a drug be fairly soluble in the mobile phase; this can be a major challenge in work with drugs that have only limited solubility in water. To overcome this issue, I developed procedures that could be used to dissolve such drugs in aqueous buffers at levels that were appropriate for HPAC. These methods utilized lower concentrations of the drugs and required additional steps for preparation, such as extended periods of stirring, sonication and heating. The limited solubility of these drugs also posed challenges when profiling the interactions of these drugs with HSA. For example, the interactions of glibenclamide and HSA were found to involve an additional non-polar and high affinity site that had not been noted previously for more soluble drugs in the same class. In addition, work with the low solubility drugs glipizide and glimepiride indicated that these agents interacted allosterically with a probe that was used to test for binding at Sudlow site I of HSA, leading to the need for additional competition studies.
Where do you see your career in bioanalysis taking you?
My current long-term goal is to be able to pursue a research career in bioanalysis in an academic environment as a chemistry professor or as a research chemist at a government agency. I would like to continue research in developing new tools and techniques for the characterization of metabolic diseases such as diabetes. I believe that there is a need to better characterize these diseases and to provide physicians and the pharmaceutical industry with more complete information on the effects of this disease to help them develop and deliver more effective treatments to patients. At the same time, however, I am also committed to sharing my knowledge of bioanalysis with others. I believe that teaching and mentoring new scientists or students about the techniques that are used in bioanalysis is important to keep the progress of research alive for the future. New scientists and students will bring in new ideas and technological advancements that have the possibility of overcoming many of current challenges that are present in bioanalysis. Therefore, the views and input of these new scientists and students are also needed to help us be able to better understand and characterize metabolic diseases, their effects and their treatment.
How do you envisage the field of bioanalysis evolving in the future?
I envision the field of bioanalysis evolving into an area of personalized medicine. The development of new techniques and tools for such work offers the capability of being able to diagnose and treat health problems efficiently and with an optimum treatment plan for each patient. I believe that the time that it takes for a patient to receive a diagnosis and effective treatment will also decrease with advancements in bioanalysis. By using small representative samples from patients, physicians and scientists should be able in the future to use improved tools and techniques, such as point of care (POC) devices, to provide the patient with a personalized treatment plan. These POC devices could be used to quickly screen through different drug classes to provide a treatment that is personalized to the patient’s health condition. This process, in turn, should decrease the amount of resources that are required to select or adjust the patient’s treatment regimen and should allow for more effective management of the patient’s disease. The information obtained from POC devices could also be used by the pharmaceutical industry to develop more effective drugs to meet the health needs of individuals.
Please list up to five of your publications in the field of bioanalysis:
1. Matsuda R, Li Z, Zheng X, Hage DS. Analysis of the binding by glimepiride to normal or glycated human serum albumin using high performance affinity chromatography. J. Chromatogr. A Submitted (2015).
2. Matsuda R, Li Z, Zheng X, Hage DS. Analysis of glipizide binding to normal and glycated human serum albumin by high performance affinity chromatography. Anal. Bioanal. Chem. Submitted (2015).
3. Matsuda R, Kye S, Anguizola J, Hage DS. Studies of drug interactions with glycated human serum albumin by high performance affinity chromatography. Rev. Anal. Chem. 33, 79—94 (2014).
4. 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).
5. Matsuda R, Anguizola J, Joseph KS, Hage DS. High-performance affinity chromatography and the analysis of drug interactions with modified proteins: Binding of gliclazide with glycated human serum albumin. Anal. Bioanal. Chem. 401, 2811—2819 (2011).
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.
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).
This paper illustrates my research and interests in bioanalysis. First, it utilizes the various procedures I have developed for work in binding studies with drugs that have limited solubility in aqueous solutions. This paper also shows how I have used HPAC as a tool to examine the binding of non-polar drugs to modified proteins such as glycated HSA. These studies, in turn, provided a complete binding profile for this protein with drugs like glibenclamide. In addition, the results of this work provided a quantitative analysis of the changes in binding that arose from protein glycation, as occurs during diabetes.
