2016 New Investigator: Casey Burton
Nominee:
Nominated By:
Supporting Comments:
What made you choose a career in bioanalysis?
My interest in cancer biomarker discovery stems from a dear friend who recently lost her seventh battle with recalcitrant breast cancer. Her perseverance continues to inspire my search for novel metabolic biomarkers and their eventual application in accessible, noninvasive screening technologies. My appreciation for this field has only widened through the exciting interplay between analytical chemistry, clinical chemistry and biochemistry. However, the most rewarding aspects of my research involve the personal stories and appreciation given by cancer patients and their families who participate in our clinical studies, continually reminding me that my work can make a significant real-world impact.
Describe the main highlights of your bioanalytical research, and its importance to the bioanalytical community.
My work aims at the application of urinary metabolomics to cancer biomarker discovery and early cancer screening. Specifically, I have developed multiplexed methodologies for the quantitation of putative biomarkers, such as pteridines, sarcosine, metals and modified nucleosides using a variety of instrumental platforms. My proof-of-concept study with urinary metals holds special significance as the first major epidemiological investigation of urinary metals in relation to cancer. My work with normalizing urinary biomarkers to urine concentration-dilution through surrogate measures such as urine specific gravity and metabolic precursors represents another major contribution to the community.
Similarly, I have contributed to several major breakthroughs in pteridine bioanalysis, including comparative studies of several commonly used sample preparation techniques, HPLC-MS/MS separation techniques for 15 pteridine derivatives, which included five structural isomers, and detailed information on the circadian rhythms of pteridine excretion into urine. The new understanding provided by this research is currently being used to support pteridine biomarker validation in national clinical trials. Beyond analytical methodologies, I have contributed to the development of a patented new form of capillary electrophoresis – laser-induced fluorescence that features improved analytical selectivity, multiplexing capacity and cost-effectiveness to support noninvasive point-of-care cancer screening in clinical settings.
What is the impact of your work beyond your home laboratory?
The analytical methodologies I have developed for putative cancer biomarkers have been used to support several related clinical trials. For example, a recently concluded trial with Mercy Breast Center (Springfield, MO, USA) examined the association between urinary pteridine levels and risk for developing breast cancer using my HPLC-MS/MS technique. This same technique has been used to study pteridine molecular epidemiology in relation to prostate, bladder and ovarian cancers in similar studies in the USA.
However, the greatest impact of my work involves my contributions to a now licensed technology that innovatively improves upon capillary electrophoresis – laser-induced fluorescence for enhanced selectivity. This technology is being developed and deployed in clinical trials in North America, Europe and Asia as a high-throughput diagnostic screening device for a range of pathologies, including cancer, traumatic brain injury and metabolic syndromes. The implementation of this bioanalytical technology and its related translational research has been especially rewarding.
Describe the most difficult challenge you have encountered in the laboratory and how you overcame it.
Pteridines have evoked considerable interest from the bioanalytical community owing to their prominent roles in human health and disease. Clinical evidence to support pteridines as putative cancer biomarkers, including my own, has often been inconclusive owing to the problematic practice of using inconsistent sample pretreatments and creatinine as a urine concentration-dilution marker. My recent work with pteridines has attempted to standardize pteridine bioanalysis through comparative studies of sample pretreatments and normalization approaches. These investigations have revealed that common oxidative pretreatments, such as manganese dioxide, were inefficient and preferentially formed non-pteridinic byproducts. These findings provided the first compelling evidence that conventional pteridine bioanalytical techniques and related clinical studies have been fundamentally flawed and that no oxidative pretreatments should be used. Similarly, molecular epidemiological investigations have generally normalized urinary pteridine levels to urinary creatinine. However, this approach can be problematic in large cross-sectional studies since creatinine can vary with muscle mass, age, gender and so forth. In a series of papers, I and my colleagues investigated the use of urine specific gravity, and more recently, certain metabolic precursors, as more accurate markers for urine concentration-dilution. Overcoming these two challenges represent significant breakthroughs in pteridine bioanalysis and application as diagnostic biomarkers.
Describe your role in bioanalytical communities/groups.
As a third year doctoral student, I have been engaged with the American Chemical Society and the Pittsburgh Conference for Analytical Chemistry and Applied Spectroscopy (Pittcon). Through both of these organizations, I have co-organized and co-presided multiple sessions at their national and international meetings on the topics of urinary metabolomics and urine cancer biomarkers, alongside other bioanalytical fields. These efforts have brought together diverse audiences that use a combination of untargeted and targeted metabolomics approaches to address a number of bioanalytical challenges.
I have also been heavily involved with the educational branch of the American Chemical Society through outreach programs with area K-12 students. Through these programs, students gain hands-on exposure to advanced research instrumentation, analytical method design and development and real-world applications of bioanalysis.
Please list up to five of your publications in the field of bioanalysis:
- Burton C, Dan Y, A. Donovan A et al. Urinary metallomics as a novel biomarker discovery platform: breast cancer as a case study. Clinica Chimica Acta 452, 142–148 (2016).
- Burton C, Weng R, Yang L, Bai Y, Liu H, Ma Y. High-throughput intracellular pteridinic profiling by liquid chromatography – quadrupole time-of-flight mass spectrometry. Analytica Chimica Acta 853, 442—450 (2015).
- Burton C, Shi H, Ma Y. Simultaneous detection of six urinary pteridines and creatinine by ultra-fast liquid chromatography-tandem mass spectrometry for clinical breast cancer detection. Analytical Chemistry 85(22), 11137–11145 (2013).
- Burton C, Shi H, Ma Y. Normalization of urinary pteridines by urine specific gravity for early cancer detection. Clinica Chimica Acta 435, 42–47 (2014).
- Burton C, Gamagedara S, Ma Y. A novel enzymatic technique for determination of sarcosine in urine samples. Analytical Methods 4, 141–146 (2012).
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.
My publication titled “High-Throughput Intracellular Pteridinic Profiling by Liquid Chromatography – Quadrupole Time-of-Flight Mass Spectrometry” highlights several aspects of my bioanalytical career. Notably, this publication resulted from a National Science Foundation East Asia and Pacific Summer Institutes Fellowship that enabled me to conduct collaborative international research at Peking University in Beijing, China. The work itself addresses my ability to overcome bioanalytical challenges, including comprehensive pteridine extraction and quantitation in cell lysates. Finally, the work highlights the translational capacity of my work, as this methodology is now being used to elucidate the cellular mechanisms of pteridines in cancer development and progression.
Find out more about this year’s New Investigator Award, the prize, the judging panel and the rest of our nominees.
