Young Investigator
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Announcing our finalists! Held in association with Waters and the European Bioanalysis Forum
Each year, Bioanalysis and Bioanalysis Zone run the Young Investigator Award to identify and reward promising early-career researchers in our community. This year, 12 young scientists were nominated for the award and their profiles have been featured on our sister website, Bioanalysis Zone. Our Advisory Panel helped us narrow down the nominees to the five most exceptional candidates.
We are delighted to present our five finalists for the 2015 Bioanalysis Young Investigator Award (in alphabetical order): • Casey Burton (Missouri University of Science and Technology); • Judit Marsillach (University of Washington); • Yu Shrike Zhang (Harvard Medical School); • Weian Zhao (University of California); • Xiwei Zheng (University of Nebraska-Lincoln). You can view the finalists’ mini profiles below. To view their full profiles and short presentation, please go to www.bioanalysis-zone.com. The award will be presented at the EBF Open Symposium in Barcelona, Spain (November 18–20). The winner will receive a 1-year subscription to Bioanalysis, complementary open access publication of their next accepted paper, and US$1000 courtesy of our sponsor Waters Corporation. part of
10.4155/BIO.15.90 © 2015 Future Science Ltd
Bioanalysis (2015) 7(13), 1667–1673
ISSN 1757-6180
1667
Young Investigator
Announcing our finalists
Casey Burton Supporting Comments: I am writing to provide Casey Burton my strongest recommendation to receive the Bioanalysis Young Investigators Award. As an undergraduate student and now a graduate researcher, he has published nine bioanalytical papers (six as first author; three as second author), has an additional five in preparation, has delivered 28 research presentations and has received two NSF Fellowships including the prestigious NSF Graduate Research Fellowship. He is undoubtedly the most productive and capable researcher I have mentored in my 30 years of university-level teaching and research. Casey has already developed a strong presence in the bioanalytical community where he has co-authored two editorials, presided a session at the 2015 Pittcon international conference, is a co-editor for a special issue of Current Analytical Chemistry and will co-chair a symposium at the national American Chemical Society Conference this fall. He displays a remarkable scientific aptitude that has led to several novel insights in the area of biomarker discovery and validation that will undoubtedly benefit the bioanalytical field as well as human health. I am confident that Casey will make an exceptional bioanalytical leader in the future and this award will provide well-deserved recognition and encouragement to continue his research endeavors. Nominated by: Y Ma, Missouri University of Science & Technology, 320 Schrenk Hall, 400 West 11th Street, Rolla, MO 65409, USA; Tel.: +1 573 341 6620; [email protected]
QQ Describe the main highlights of your bioanalytical research & its importance to the bioanalytical community? My research efforts aim at the development of novel, cost-effective bioanalytical techniques for clinical analysis of emerging urinary biomarkers for earlier cancer detection. Urine-based cancer screening represents a new direction for cancer diagnostics that is particularly attractive for its noninvasive modality, abundant specimen volumes and relatively simple matrices compared with serum and tissue analyses. I have found the emerging area of urinary metabolomics to be especially engaging as a powerful, new platform for cancer biomarker discovery and validation. Here at Missouri S&T, I developed targeted bioanalytical techniques for several biomarker panels including sarcosine and alanine, 25 urinary and cellular pteridines, the urine metallome and others. My research frequently encounters and addresses emerging challenges to these new fields such as isomeric interferences, panel size limitations and selection of appropriate surrogate normalization biomarkers for renal function. My recent contributions to overcoming urine normalization factors, particularly in regard to urine specific gravity, have been especially impactful on the bioanalytical community, evidenced by Letters to Editors, numerous citations, over 2000 article downloads and a top viewed paper in Analytical Methods. Finally, my bioanalytical techniques have directly initiated several clinical trials at Mercy Hospital to determine clinical applicability of pteridine and metallomic cancer biomarkers.
QQ Describe the most difficult challenge you have encountered in the laboratory & how you overcame it?
Pteridine bioanalysis is notoriously complicated by trace concentrations, three oxidative states, poor solubility in common solvents and sensitivity to heat and light. These challenges are even more apparent for intracellular pteridines, which has been a key roadblock to establishing biological relevance for these cancer biomarkers. For this reason, I received an NSF EAPSI Fellowship to address these challenges at Peking University (Beijing, China). Unlike other techniques that fully oxidize pteridines to a single state, my technique sought to preserve their native speciation which may provide new insights to potential pathophysiological mechanisms. However, my use of ammonium hydroxide as a solubility enhancer further complicated these efforts. Dithiothreitol, an antioxidant was eventually selected and optimized to counter these problematic effects and permit native pteridine profiling. Yet, there still remained the substantial challenge of effectively extracting the intracellular pteridines. Extractive techniques had never been described for pteridines while common metabolite extraction methods would adversely promote oxidative processes. So, I developed a method based on techniques used for similarly polar nucleosides that eventually involved cryogenic cell lysis and enough ammonium hydroxide and dithiothreitol to carefully extract the fragile pteridine species. These advances are now being used to establish biological relevance of pteridines in cancer.
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Bioanalysis (2015) 7(13)
future science group
Announcing our finalists
Young Investigator
Judit Marsillach Supporting Comments: It is a pleasure to provide supporting comments for this outstanding nominee. J Marsillach has accomplished two major feats in analytical protein chemistry in the past few years. First, she has developed a protocol for characterizing organophosphate adducts to active site serines of biomarker proteins including butyrylcholinesterase, acetylcholinesterase, acylpeptide hydrolase and carboxylesterase using rapid immunomagnetic bead isolation protocols followed by LC–MS analysis of modified proteins. In the case of butyrylcholinesterase, she was able to measure as little as a 2% modification of the active site serine by chlorpyrifos oxon. She is able to do these analyses from dried blood spot samples, which will dramatically improve OP exposure analyses. Her most recent accomplishment has been quantification of paraoxonase-3 in human serum. In her most recent publication, she demonstrated a good correlation between the MS measurements and quantitative Western blot analysis. Even more remarkable is J Marsillach’s publication record – she has published more than 60 papers, a unique accomplishment for someone so early in their career. To date, J Marsillach has been able to master all of the challenges that she has taken on. Her training in LC–MS analyses will provide a background for generating more breakthroughs in the future. Nominated by: Clement E Furlong, Departments of Medicine (Division of Medical Genetics) & Genome Sciences, University of Washington, 1959 NE Pacific Street, HSB Room I-204, Box 357720, Seattle, WA 98195, USA; Tel.: +1 206 543 1193; [email protected].
QQ Describe the main highlights of your bioanalytical research & its importance to the bioanalytical community? My primary research interest is in the area of environmental health and chronic human disease, with an emphasis in oxidative stress and adductomics. In the environmental health field, my work is focused on characterizing adducted biomarker proteins from plasma or erythrocytes to monitor exposures to organophosphorus compounds. The biomonitoring of these exposures lacks proper methodology. The automatable methods that I have developed to monitor organophosphorus exposures combine immunoprecipitation with MS, providing a ten-fold increase in sensitivity, together with use of state-of-the-art equipment and the potential to be readily translated to the clinical laboratory. In addition, the blood samples can be collected as dried blood spots, facilitating collection, shipment and storage of the samples. In the chronic human disease field, I have been able to accurately quantify 18 proteins by MS from high-density lipoproteins from both healthy subjects and patients with autoimmune diseases. I have demonstrated a good correlation with Western blot analysis, providing more evidence that MS has the potential to replace immunoassays. My next step on this field will be to demonstrate that oxidative stress products adduct proteins, with an emphasis on the paraoxonases enzymes and how these modified proteins can become relevant biomarkers of disease development.
QQ Where do you see your career in bioanalysis taking you?
I feel my career in bioanalysis is taking me to translating laboratory discoveries into methods and treatments that can benefit human health. The work that I am doing in adductomics on biomarker proteins will allow for more rapid and accurate disease diagnostics. Proteomics is an emerging method not only for studying posttranslational modification of proteins, but also for accurate protein quantification and characterization of modified biomarkers of exposure and disease. The focus of the mass spectrometric bioanalysis of the experiments that I am conducting represents a significant progress in the fields of laboratory medicine and epidemiology, developing useful methods for diagnosing and evaluating disease states in human health and exposures to xenobiotics. I also feel that the bioanalysis field has matured significantly in the past years and it is progressing at fast pace, with new technologies and more sensitive, accurate and efficient instruments being developed every year. For instance, techniques such as immunohistochemistry and MS can now be combined into mass spectrometry immunohistochemistry, a new approach that I am very excited to include in my future experiments. Financial & competing interests disclosure J Marsillach’s research was supported by NIH Grants ES009883, ES004696, ES006901/EPA RD-83451401; NIOSH/PNASHOHO7544 and gifts from pilots and crew unions.
future science group
www.future-science.com
1669
Young Investigator
Announcing our finalists
Yu Shrike Zhang Supporting Comments: I am writing to nominate an outstanding scientist, Yu Shrike Zhang, for Bioanalysis Zone Young Investigator Award. Zhang’s exceptional achievement and long-time dedication to the bioanalytical community makes him well deserve this honor. During his doctoral research he demonstrated excellence in bioanalysis by bringing photoacoustic microscopy to the field of regenerative medicine. He solved one of the greatest challenges by making noninvasive, high resolution and volumetric visualization of engineered tissues possible. Such technology is now appreciated by many tissue engineers worldwide and has inspired more to follow. Zhang’s postdoctoral training in my laboratory is centered on designing microfluidic electrochemical biosensors. He has developed a most bleeding-edge organs-on-a-chip platform for fully automated monitoring of biomolecule secretion and drug/toxins screening. Such a platform is fabricated based upon sophisticated organ bioreactors, valve/ pumping systems and biosensors, which has been highlighted by major media such as BBC and CBC. Zhang’s future direction is largely concentrated on bioanalysis as well: he plans to construct patient-specific tumor models integrated with these sensors for personalized cancer theranostics. In all, Zhang exceeds the challenging requirements and expectations for this award in many ways. His dedication, intelligence and accomplishments should surely earn him the award. Nominated by: Ali Khademhosseini, Brigham & Women’s Hospital, Harvard Medical School, Harvard-MIT, Division of Health Sciences & Technology, 65 Landsdowne Street, Rm. 265, Cambridge, MA 02139, USA; Tel.: +1 617 768 8395; [email protected]
QQ Describe the main highlights of your bioanalytical research & its importance to the bioanalytical community? The main highlights of my bioanalytical research lie in that I have always been seeking the integration of cutting-edge techniques from multiple disciplines to create novel bioanalytical tools for applications in biomedicine. During my PhD studies I introduced photoacoustic microscopy (PAM) to the field of regenerative medicine as a new imaging modality for characterizing engineered tissues. PAM is a recently developed, potent technique that relies on the collection of photoacoustic signals generated from transient expansion of an absorbing sample illuminated by pulse laser irradiation. PAM breaks through the optical diffusion limit and provides imaging depths up to approximately 7 cm, with an excellent depth-to-resolution ratio of approximately 200. I immediately realized the advantages of PAM and became the first researcher to ever bring PAM to regenerative medicine, and my pilot researches have opened an entirely new avenue for the field by providing an unprecedented approach to analyze thick engineered tissues at high resolution and a completely noninvasive manner. For my postdoctoral training, I developed an unparalleled biosensor platform by integrating microfluidic circuitry, valve/flow control system and electrochemical biosensors for fully automated, continual and multiplexed monitoring of organ-secreted biomarkers and biological species, which has a potential to transform the field by providing high-capacity biosensing.
QQ How do you envisage the field of bioanalysis evolving in the future?
The beauty of bioanalysis stands upon its high accuracy and precision in analyzing desired and only desired biological species of interests. The analysis should be specific, not interfering with background signals. In addition, a biosensor should possess superb sensitivity that is matched with its proposed application and cost. Based on these premise, however, the world nowadays requires much more than single analyses. For example, millions of different new pharmaceutical compounds are being developed and tested every year, marking the ineffectiveness of the conventional manual measurements; on battlefield, antidotes against biological and chemical weapons need to be screened in large scales to ensure fast response towards prompt cures of the affected soldiers; with fast economic boost particularly in developing countries, environmental toxins of infinite species need to be analyzed to reduce their impact on nature and human health. All these unprecedented challenges require the development of fully automated systems that are able to perform parallel analyses of large pools of biological agents and ideally, minimize human efforts in order to boost the throughput of the sensors. The sensors should also be integrated and miniaturized to allow for high-throughput analysis at minimum sample volume and cost.
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Bioanalysis (2015) 7(13)
future science group
Announcing our finalists
Young Investigator
Weian Zhao Supporting Comments: It is with great pleasure to give my strongest support to W Zhao for your award. W Zhao worked as a HFSP postdoctoral fellow in my group from 2008 to 2011 before he became independent at UC Irvine. W Zhao is a leader in the development of in vitro diagnostics and biosensor technologies to study biology in vivo. He has published >50 journal articles in highly respected journals. In my laboratory, he developed cell-surface sensor technologies to study transplanted stem cells in vivo. More recently, in his independent laboratory, he invented the IC 3D technology that can rapidly detect single bacteria from unprocessed blood that was previously an unmet need. W Zhao’s innovation has been recognized by the MIT’s Technology Review TR35 Award: the world’s top 35 innovators under the age of 35 and the NIH Director’s New Innovator Award. Weian is also determined to serve the bioanalytical field: he has served on the editorial boards of Interface Focus and Nanotechnology, and co-chaired sessions in numerous conferences including 24th World Congress on Biosensors and MicroTAS 2014. Therefore, W Zhao has and will continue to make major impact in the bioanalytical field. He is an outstanding candidate by all measures for this award. Nominated by: Jeffrey M Karp, Associate Professor of Medicine, Brigham & Women’s Hospital, Harvard Medical School, Landsdowne Street, PRB 313 Cambridge, MA 02139, USA; Tel.: +1 617 817 9174; [email protected]
QQ Describe the main highlights of your bioanalytical research & its importance to the bioanalytical community? Throughout my career, I have been focused on the development of bioanalytical tools that allow us to better address unmet biomedical questions, especially those that can be quickly translated to the market to help people. During my PhD studies, I invented a simple-to-use paper based strip test using DNA aptamer sensors, which was awarded a Natural Sciences and Engineering Research Council Innovation Challenge Award. This technology is now being commercialized in a start-up company in Canada for detection of food pathogens. In my postdoctoral study, I developed a novel approach to use naturally homing stem cells to deliver fluorescent sensors to cell microenvironments in vivo, which represented a new paradigm in the study of cell signaling and communication in native niches. Most recently, in my own laboratory, we developed the Integrated Comprehensive Droplet Digital Detection (IC 3D) that introduces a new paradigm for rapid detection of low-abundance biomarkers directly from unprocessed complex biological samples. The IC 3D technology, which has been licensed to Velox Biosystems, a start-up company that I founded recently, has great potential to address a long-standing unmet need of rapid detection of bloodstream infections and antibiotic resistance that represents one of the greatest threats to humankind.
QQ Describe the most difficult challenge you have encountered in the laboratory & how you overcame it?
My PhD thesis aimed to develop a test that could specifically detect single bacteria from a large volume of complex media within 60 min. The most difficult challenge was a technical one: it was extremely challenging to meet all five key analytical parameters including sensitivity, specificity, assay time, throughput and robustness all at once. These parameters are seemingly incompatible: for instance, if you want to achieve single-cell sensitivity, you will need to enrich them to a detectable level, which compromises assay time. My ‘aha’ moment to conceive the IC 3D technology that overcomes the challenge resulted from conversations with researchers from different fields, including engineering and physics. In the IC 3D assay, unprocessed samples are mixed with the fluorescent biosensors within a microfluidic channel, which are rapidly encapsulated into billions of individual picoliter droplets. The sensors will fluoresce in the droplets that contain bacterium. The droplets can then be counted by a high-throughput particle counter that can robustly detect single fluorescent droplets from millileter volumes within several minutes. What I learned is that interdisciplinary and collaborative research is an effective strategy to address the biggest challenges and that the real solution to a big problem should be simple. Financial & competing interests disclosure W Zhao is the founder of Velox Biosystems, LLC, a start-up company that aims to develop and commercialize rapid and sensitive diagnostics and bioassays.
future science group
www.future-science.com
1671
Young Investigator
Announcing our finalists
Xiwei (Emmi) Zheng Supporting Comments: I have enjoyed working with Xiwei (Emmi) as she has worked on her doctorate degree in chemistry. Emmi is a highly effective, independent and hardworking researcher, who has also been extremely productive in her work. For instance, in one of her first projects she created a multidimensional separation system that could simultaneously measure the biologically active fractions of several related drugs in the same sample. This was a challenging project, but Emmi was able to create a powerful system that can be adapted for use in many other applications, ranging from rapid biointeraction studies to pharmaceutical analysis and personalized medicine. For instance, she has extended these methods to examine the binding by drugs used to treat Type II diabetes with both normal and glycated forms of human serum albumin. She has also used her approach to measure the free fractions of drugs in serum and to examine binding by the hormone testosterone with its serum transport proteins. I have high expectations for Emmi in her future career, and I believe that her work has already had a big impact in the field of bioanalysis, as well as in the study of complex systems of clinical, pharmaceutical or biomedical interest. Nominated by: David S Hage, Chemistry Department, University of Nebraska-Lincoln, 704 Hamilton Hall, Lincoln, NE 68588, USA; Tel.: +1 402 472 2744; [email protected]
QQ Describe the main highlights of your bioanalytical research & its importance to the bioanalytical community? My research has involved studies of the interactions between drugs/hormones and serum proteins by 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 multidimensional system, this method was also adapted to measure free fraction of drugs in samples such as human serum. The techniques developed in my research are label-free, have short analysis times (i.e., minutes) and need only microliter amounts of a sample. In related work, I developed a new immobilization method for making HPAC columns, which gives up to a twofold 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.
QQ How do you envisage the field of bioanalysis evolving in the future?
I think the field of bioanalysis will continue to develop and improve in measuring smaller amounts of samples and in shorter analysis time. I also expect increases in sensitivity and selectivity to continue for the analysis of trace targets in clinical samples. For these developments to occur, 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 and medicine as well as from 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 a strong knowledge of various techniques and methods, but should also be able to break through the current limits that exist within these separate areas. I believe through these efforts that bioanalysis will undergo a dramatic development and continue to be an important field in providing information for us to better understand the various processes that occur in biological systems. Financial & competing interests disclosure X Zheng’s work was supported, in part, by the National Institutes of Health under Grants R01 GM044931 and R01 DK069629, and by the National Science Foundation/EPSCoR Program under grant EPS-1004094.
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Announcing our finalists
Young Investigator
Financial & competing interests disclosure Apart from the above disclosures from J Marsillach, W Zhao and X Zheng, the authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
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1673
For reprint orders, please contact [email protected]
Announcing our finalists! Held in association with Waters and the European Bioanalysis Forum
Each year, Bioanalysis and Bioanalysis Zone run the Young Investigator Award to identify and reward promising early-career researchers in our community. This year, 12 young scientists were nominated for the award and their profiles have been featured on our sister website, Bioanalysis Zone. Our Advisory Panel helped us narrow down the nominees to the five most exceptional candidates.
We are delighted to present our five finalists for the 2015 Bioanalysis Young Investigator Award (in alphabetical order): • Casey Burton (Missouri University of Science and Technology); • Judit Marsillach (University of Washington); • Yu Shrike Zhang (Harvard Medical School); • Weian Zhao (University of California); • Xiwei Zheng (University of Nebraska-Lincoln). You can view the finalists’ mini profiles below. To view their full profiles and short presentation, please go to www.bioanalysis-zone.com. The award will be presented at the EBF Open Symposium in Barcelona, Spain (November 18–20). The winner will receive a 1-year subscription to Bioanalysis, complementary open access publication of their next accepted paper, and US$1000 courtesy of our sponsor Waters Corporation. part of
10.4155/BIO.15.90 © 2015 Future Science Ltd
Bioanalysis (2015) 7(13), 1667–1673
ISSN 1757-6180
1667
Young Investigator
Announcing our finalists
Casey Burton Supporting Comments: I am writing to provide Casey Burton my strongest recommendation to receive the Bioanalysis Young Investigators Award. As an undergraduate student and now a graduate researcher, he has published nine bioanalytical papers (six as first author; three as second author), has an additional five in preparation, has delivered 28 research presentations and has received two NSF Fellowships including the prestigious NSF Graduate Research Fellowship. He is undoubtedly the most productive and capable researcher I have mentored in my 30 years of university-level teaching and research. Casey has already developed a strong presence in the bioanalytical community where he has co-authored two editorials, presided a session at the 2015 Pittcon international conference, is a co-editor for a special issue of Current Analytical Chemistry and will co-chair a symposium at the national American Chemical Society Conference this fall. He displays a remarkable scientific aptitude that has led to several novel insights in the area of biomarker discovery and validation that will undoubtedly benefit the bioanalytical field as well as human health. I am confident that Casey will make an exceptional bioanalytical leader in the future and this award will provide well-deserved recognition and encouragement to continue his research endeavors. Nominated by: Y Ma, Missouri University of Science & Technology, 320 Schrenk Hall, 400 West 11th Street, Rolla, MO 65409, USA; Tel.: +1 573 341 6620; [email protected]
QQ Describe the main highlights of your bioanalytical research & its importance to the bioanalytical community? My research efforts aim at the development of novel, cost-effective bioanalytical techniques for clinical analysis of emerging urinary biomarkers for earlier cancer detection. Urine-based cancer screening represents a new direction for cancer diagnostics that is particularly attractive for its noninvasive modality, abundant specimen volumes and relatively simple matrices compared with serum and tissue analyses. I have found the emerging area of urinary metabolomics to be especially engaging as a powerful, new platform for cancer biomarker discovery and validation. Here at Missouri S&T, I developed targeted bioanalytical techniques for several biomarker panels including sarcosine and alanine, 25 urinary and cellular pteridines, the urine metallome and others. My research frequently encounters and addresses emerging challenges to these new fields such as isomeric interferences, panel size limitations and selection of appropriate surrogate normalization biomarkers for renal function. My recent contributions to overcoming urine normalization factors, particularly in regard to urine specific gravity, have been especially impactful on the bioanalytical community, evidenced by Letters to Editors, numerous citations, over 2000 article downloads and a top viewed paper in Analytical Methods. Finally, my bioanalytical techniques have directly initiated several clinical trials at Mercy Hospital to determine clinical applicability of pteridine and metallomic cancer biomarkers.
QQ Describe the most difficult challenge you have encountered in the laboratory & how you overcame it?
Pteridine bioanalysis is notoriously complicated by trace concentrations, three oxidative states, poor solubility in common solvents and sensitivity to heat and light. These challenges are even more apparent for intracellular pteridines, which has been a key roadblock to establishing biological relevance for these cancer biomarkers. For this reason, I received an NSF EAPSI Fellowship to address these challenges at Peking University (Beijing, China). Unlike other techniques that fully oxidize pteridines to a single state, my technique sought to preserve their native speciation which may provide new insights to potential pathophysiological mechanisms. However, my use of ammonium hydroxide as a solubility enhancer further complicated these efforts. Dithiothreitol, an antioxidant was eventually selected and optimized to counter these problematic effects and permit native pteridine profiling. Yet, there still remained the substantial challenge of effectively extracting the intracellular pteridines. Extractive techniques had never been described for pteridines while common metabolite extraction methods would adversely promote oxidative processes. So, I developed a method based on techniques used for similarly polar nucleosides that eventually involved cryogenic cell lysis and enough ammonium hydroxide and dithiothreitol to carefully extract the fragile pteridine species. These advances are now being used to establish biological relevance of pteridines in cancer.
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Bioanalysis (2015) 7(13)
future science group
Announcing our finalists
Young Investigator
Judit Marsillach Supporting Comments: It is a pleasure to provide supporting comments for this outstanding nominee. J Marsillach has accomplished two major feats in analytical protein chemistry in the past few years. First, she has developed a protocol for characterizing organophosphate adducts to active site serines of biomarker proteins including butyrylcholinesterase, acetylcholinesterase, acylpeptide hydrolase and carboxylesterase using rapid immunomagnetic bead isolation protocols followed by LC–MS analysis of modified proteins. In the case of butyrylcholinesterase, she was able to measure as little as a 2% modification of the active site serine by chlorpyrifos oxon. She is able to do these analyses from dried blood spot samples, which will dramatically improve OP exposure analyses. Her most recent accomplishment has been quantification of paraoxonase-3 in human serum. In her most recent publication, she demonstrated a good correlation between the MS measurements and quantitative Western blot analysis. Even more remarkable is J Marsillach’s publication record – she has published more than 60 papers, a unique accomplishment for someone so early in their career. To date, J Marsillach has been able to master all of the challenges that she has taken on. Her training in LC–MS analyses will provide a background for generating more breakthroughs in the future. Nominated by: Clement E Furlong, Departments of Medicine (Division of Medical Genetics) & Genome Sciences, University of Washington, 1959 NE Pacific Street, HSB Room I-204, Box 357720, Seattle, WA 98195, USA; Tel.: +1 206 543 1193; [email protected].
QQ Describe the main highlights of your bioanalytical research & its importance to the bioanalytical community? My primary research interest is in the area of environmental health and chronic human disease, with an emphasis in oxidative stress and adductomics. In the environmental health field, my work is focused on characterizing adducted biomarker proteins from plasma or erythrocytes to monitor exposures to organophosphorus compounds. The biomonitoring of these exposures lacks proper methodology. The automatable methods that I have developed to monitor organophosphorus exposures combine immunoprecipitation with MS, providing a ten-fold increase in sensitivity, together with use of state-of-the-art equipment and the potential to be readily translated to the clinical laboratory. In addition, the blood samples can be collected as dried blood spots, facilitating collection, shipment and storage of the samples. In the chronic human disease field, I have been able to accurately quantify 18 proteins by MS from high-density lipoproteins from both healthy subjects and patients with autoimmune diseases. I have demonstrated a good correlation with Western blot analysis, providing more evidence that MS has the potential to replace immunoassays. My next step on this field will be to demonstrate that oxidative stress products adduct proteins, with an emphasis on the paraoxonases enzymes and how these modified proteins can become relevant biomarkers of disease development.
QQ Where do you see your career in bioanalysis taking you?
I feel my career in bioanalysis is taking me to translating laboratory discoveries into methods and treatments that can benefit human health. The work that I am doing in adductomics on biomarker proteins will allow for more rapid and accurate disease diagnostics. Proteomics is an emerging method not only for studying posttranslational modification of proteins, but also for accurate protein quantification and characterization of modified biomarkers of exposure and disease. The focus of the mass spectrometric bioanalysis of the experiments that I am conducting represents a significant progress in the fields of laboratory medicine and epidemiology, developing useful methods for diagnosing and evaluating disease states in human health and exposures to xenobiotics. I also feel that the bioanalysis field has matured significantly in the past years and it is progressing at fast pace, with new technologies and more sensitive, accurate and efficient instruments being developed every year. For instance, techniques such as immunohistochemistry and MS can now be combined into mass spectrometry immunohistochemistry, a new approach that I am very excited to include in my future experiments. Financial & competing interests disclosure J Marsillach’s research was supported by NIH Grants ES009883, ES004696, ES006901/EPA RD-83451401; NIOSH/PNASHOHO7544 and gifts from pilots and crew unions.
future science group
www.future-science.com
1669
Young Investigator
Announcing our finalists
Yu Shrike Zhang Supporting Comments: I am writing to nominate an outstanding scientist, Yu Shrike Zhang, for Bioanalysis Zone Young Investigator Award. Zhang’s exceptional achievement and long-time dedication to the bioanalytical community makes him well deserve this honor. During his doctoral research he demonstrated excellence in bioanalysis by bringing photoacoustic microscopy to the field of regenerative medicine. He solved one of the greatest challenges by making noninvasive, high resolution and volumetric visualization of engineered tissues possible. Such technology is now appreciated by many tissue engineers worldwide and has inspired more to follow. Zhang’s postdoctoral training in my laboratory is centered on designing microfluidic electrochemical biosensors. He has developed a most bleeding-edge organs-on-a-chip platform for fully automated monitoring of biomolecule secretion and drug/toxins screening. Such a platform is fabricated based upon sophisticated organ bioreactors, valve/ pumping systems and biosensors, which has been highlighted by major media such as BBC and CBC. Zhang’s future direction is largely concentrated on bioanalysis as well: he plans to construct patient-specific tumor models integrated with these sensors for personalized cancer theranostics. In all, Zhang exceeds the challenging requirements and expectations for this award in many ways. His dedication, intelligence and accomplishments should surely earn him the award. Nominated by: Ali Khademhosseini, Brigham & Women’s Hospital, Harvard Medical School, Harvard-MIT, Division of Health Sciences & Technology, 65 Landsdowne Street, Rm. 265, Cambridge, MA 02139, USA; Tel.: +1 617 768 8395; [email protected]
QQ Describe the main highlights of your bioanalytical research & its importance to the bioanalytical community? The main highlights of my bioanalytical research lie in that I have always been seeking the integration of cutting-edge techniques from multiple disciplines to create novel bioanalytical tools for applications in biomedicine. During my PhD studies I introduced photoacoustic microscopy (PAM) to the field of regenerative medicine as a new imaging modality for characterizing engineered tissues. PAM is a recently developed, potent technique that relies on the collection of photoacoustic signals generated from transient expansion of an absorbing sample illuminated by pulse laser irradiation. PAM breaks through the optical diffusion limit and provides imaging depths up to approximately 7 cm, with an excellent depth-to-resolution ratio of approximately 200. I immediately realized the advantages of PAM and became the first researcher to ever bring PAM to regenerative medicine, and my pilot researches have opened an entirely new avenue for the field by providing an unprecedented approach to analyze thick engineered tissues at high resolution and a completely noninvasive manner. For my postdoctoral training, I developed an unparalleled biosensor platform by integrating microfluidic circuitry, valve/flow control system and electrochemical biosensors for fully automated, continual and multiplexed monitoring of organ-secreted biomarkers and biological species, which has a potential to transform the field by providing high-capacity biosensing.
QQ How do you envisage the field of bioanalysis evolving in the future?
The beauty of bioanalysis stands upon its high accuracy and precision in analyzing desired and only desired biological species of interests. The analysis should be specific, not interfering with background signals. In addition, a biosensor should possess superb sensitivity that is matched with its proposed application and cost. Based on these premise, however, the world nowadays requires much more than single analyses. For example, millions of different new pharmaceutical compounds are being developed and tested every year, marking the ineffectiveness of the conventional manual measurements; on battlefield, antidotes against biological and chemical weapons need to be screened in large scales to ensure fast response towards prompt cures of the affected soldiers; with fast economic boost particularly in developing countries, environmental toxins of infinite species need to be analyzed to reduce their impact on nature and human health. All these unprecedented challenges require the development of fully automated systems that are able to perform parallel analyses of large pools of biological agents and ideally, minimize human efforts in order to boost the throughput of the sensors. The sensors should also be integrated and miniaturized to allow for high-throughput analysis at minimum sample volume and cost.
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Bioanalysis (2015) 7(13)
future science group
Announcing our finalists
Young Investigator
Weian Zhao Supporting Comments: It is with great pleasure to give my strongest support to W Zhao for your award. W Zhao worked as a HFSP postdoctoral fellow in my group from 2008 to 2011 before he became independent at UC Irvine. W Zhao is a leader in the development of in vitro diagnostics and biosensor technologies to study biology in vivo. He has published >50 journal articles in highly respected journals. In my laboratory, he developed cell-surface sensor technologies to study transplanted stem cells in vivo. More recently, in his independent laboratory, he invented the IC 3D technology that can rapidly detect single bacteria from unprocessed blood that was previously an unmet need. W Zhao’s innovation has been recognized by the MIT’s Technology Review TR35 Award: the world’s top 35 innovators under the age of 35 and the NIH Director’s New Innovator Award. Weian is also determined to serve the bioanalytical field: he has served on the editorial boards of Interface Focus and Nanotechnology, and co-chaired sessions in numerous conferences including 24th World Congress on Biosensors and MicroTAS 2014. Therefore, W Zhao has and will continue to make major impact in the bioanalytical field. He is an outstanding candidate by all measures for this award. Nominated by: Jeffrey M Karp, Associate Professor of Medicine, Brigham & Women’s Hospital, Harvard Medical School, Landsdowne Street, PRB 313 Cambridge, MA 02139, USA; Tel.: +1 617 817 9174; [email protected]
QQ Describe the main highlights of your bioanalytical research & its importance to the bioanalytical community? Throughout my career, I have been focused on the development of bioanalytical tools that allow us to better address unmet biomedical questions, especially those that can be quickly translated to the market to help people. During my PhD studies, I invented a simple-to-use paper based strip test using DNA aptamer sensors, which was awarded a Natural Sciences and Engineering Research Council Innovation Challenge Award. This technology is now being commercialized in a start-up company in Canada for detection of food pathogens. In my postdoctoral study, I developed a novel approach to use naturally homing stem cells to deliver fluorescent sensors to cell microenvironments in vivo, which represented a new paradigm in the study of cell signaling and communication in native niches. Most recently, in my own laboratory, we developed the Integrated Comprehensive Droplet Digital Detection (IC 3D) that introduces a new paradigm for rapid detection of low-abundance biomarkers directly from unprocessed complex biological samples. The IC 3D technology, which has been licensed to Velox Biosystems, a start-up company that I founded recently, has great potential to address a long-standing unmet need of rapid detection of bloodstream infections and antibiotic resistance that represents one of the greatest threats to humankind.
QQ Describe the most difficult challenge you have encountered in the laboratory & how you overcame it?
My PhD thesis aimed to develop a test that could specifically detect single bacteria from a large volume of complex media within 60 min. The most difficult challenge was a technical one: it was extremely challenging to meet all five key analytical parameters including sensitivity, specificity, assay time, throughput and robustness all at once. These parameters are seemingly incompatible: for instance, if you want to achieve single-cell sensitivity, you will need to enrich them to a detectable level, which compromises assay time. My ‘aha’ moment to conceive the IC 3D technology that overcomes the challenge resulted from conversations with researchers from different fields, including engineering and physics. In the IC 3D assay, unprocessed samples are mixed with the fluorescent biosensors within a microfluidic channel, which are rapidly encapsulated into billions of individual picoliter droplets. The sensors will fluoresce in the droplets that contain bacterium. The droplets can then be counted by a high-throughput particle counter that can robustly detect single fluorescent droplets from millileter volumes within several minutes. What I learned is that interdisciplinary and collaborative research is an effective strategy to address the biggest challenges and that the real solution to a big problem should be simple. Financial & competing interests disclosure W Zhao is the founder of Velox Biosystems, LLC, a start-up company that aims to develop and commercialize rapid and sensitive diagnostics and bioassays.
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Young Investigator
Announcing our finalists
Xiwei (Emmi) Zheng Supporting Comments: I have enjoyed working with Xiwei (Emmi) as she has worked on her doctorate degree in chemistry. Emmi is a highly effective, independent and hardworking researcher, who has also been extremely productive in her work. For instance, in one of her first projects she created a multidimensional separation system that could simultaneously measure the biologically active fractions of several related drugs in the same sample. This was a challenging project, but Emmi was able to create a powerful system that can be adapted for use in many other applications, ranging from rapid biointeraction studies to pharmaceutical analysis and personalized medicine. For instance, she has extended these methods to examine the binding by drugs used to treat Type II diabetes with both normal and glycated forms of human serum albumin. She has also used her approach to measure the free fractions of drugs in serum and to examine binding by the hormone testosterone with its serum transport proteins. I have high expectations for Emmi in her future career, and I believe that her work has already had a big impact in the field of bioanalysis, as well as in the study of complex systems of clinical, pharmaceutical or biomedical interest. Nominated by: David S Hage, Chemistry Department, University of Nebraska-Lincoln, 704 Hamilton Hall, Lincoln, NE 68588, USA; Tel.: +1 402 472 2744; [email protected]
QQ Describe the main highlights of your bioanalytical research & its importance to the bioanalytical community? My research has involved studies of the interactions between drugs/hormones and serum proteins by 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 multidimensional system, this method was also adapted to measure free fraction of drugs in samples such as human serum. The techniques developed in my research are label-free, have short analysis times (i.e., minutes) and need only microliter amounts of a sample. In related work, I developed a new immobilization method for making HPAC columns, which gives up to a twofold 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.
QQ How do you envisage the field of bioanalysis evolving in the future?
I think the field of bioanalysis will continue to develop and improve in measuring smaller amounts of samples and in shorter analysis time. I also expect increases in sensitivity and selectivity to continue for the analysis of trace targets in clinical samples. For these developments to occur, 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 and medicine as well as from 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 a strong knowledge of various techniques and methods, but should also be able to break through the current limits that exist within these separate areas. I believe through these efforts that bioanalysis will undergo a dramatic development and continue to be an important field in providing information for us to better understand the various processes that occur in biological systems. Financial & competing interests disclosure X Zheng’s work was supported, in part, by the National Institutes of Health under Grants R01 GM044931 and R01 DK069629, and by the National Science Foundation/EPSCoR Program under grant EPS-1004094.
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Bioanalysis (2015) 7(13)
future science group
Announcing our finalists
Young Investigator
Financial & competing interests disclosure Apart from the above disclosures from J Marsillach, W Zhao and X Zheng, the authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
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