Dr. Robert B. (Chip) Cody received his Ph.D. from Purdue University in 1982 under the direction of Prof. Ben S, Freiser. After graduate school, he worked at Nicolet Instruments developing methods for Fourier Transform Mass Spectrometry until 1989 when he joined JEOL USA, Inc. where he is presently Product Manager for Mass Spectrometry. Among other achievements, Dr. Cody is responsible for developing the trapped-ion tandem-in-time MS/MS and MSn techniques, laser-desorption FTICR, and is coinventor of the DART ion source. He served as Vice-President for Arrangements for the American Society of Mass Spectrometry and was awarded the 2011 Anachem Award and a 2012 Purdue University Distinguished Alumni Award. He has over 100 publications and several patents, edited (with Marek Domin of Boston College) the book Ambient Ionization Mass Spectrometry, and is author of the Mass Mountaineer software suite.

It has now been 17 years since a patent was filed describing the Direct Analysis in Real Time (DART) ion source, yet no clinical applications of DART MS are currently in use. This is not to say that DART has no potential for clinical applications! As an ambient ionization method, DART has several attractive characteristics for clinical chemistry. DART analysis is rapid and robust, and can be applied to a wide range of analytes. In combination with a high-resolution and/or tandem mass spectrometer, DART can be quite sensitive and selective. Point-of-care applications are possible if DART is combined with a compact mass spectrometer.
Several promising DART applications have been reported. Because it produces a broad profile of small-molecule biomarkers, DART is well matched with chemometric analysis for speciation and classification. Two published feasibility studies have shown the potential for microbial identification using DART MS. The first (from CDC and GA Tech) used in-situ methylation and DART to identify bacterial fatty acid profiles. The second study found that free fatty acids from a simple extraction method could identify ten different pathogens. Another study from the Fernandez lab at GA Tech showed a DART method for ovarian cancer screening with statistics that showed 100% accuracy!
Clinical toxicology is another area of potential application. DART is well established for forensic drug screening. That same capability could be used to screen for drugs and toxins to guide treatment in victims of poisoning or overdose. With relatively simple sample handling methods, detection limits for drugs in body fluids are suitable for rapid screening. DART has demonstrated the potential for monitoring drug excretion kinetics and in at least one case, detection of biomarkers for disease conditions. In a recent study, we have found that DART can be combined with another ambient ionization method (Coated Blade Spray) to provide complementary data from minimal sample volumes.
So, why has DART not yet found a place in clinical chemistry? Commercially available laboratory systems have been on the market for 15 years, and portable systems are also now commercially available. Perhaps the answer is just a need for early adopters who are willing to carry out clinical validation studies, much as the VA DFS did for forensic drug screening.

Lorin Bachmann joined the VCU Department of Pathology in 2007. She currently serves as Co-Director of Clinical Chemistry, Co-Director of Point-of-Care Testing, Director of the New Kent Emergency Department Laboratory, Technical Advisor for the Operating Room Laboratory, Pathology Outreach and Clinical Trials, and Laboratory Director for multiple VCUHS outreach laboratories. Dr. Bachmann received her PhD in Molecular Medicine from the University of Virginia, followed by a fellowship in clinical chemistry and proteomics research at the University of Virginia. Dr. Bachmann is certified by the American Board of Clinical Chemistry.

Dr. Bachmann is active within the American Association for Clinical Chemistry (AACC), where she serves on the Board of Directors. She also serves as the Chair of the Chemistry and Toxicology Expert Panel for the Clinical Laboratory and Standards Institute (CLSI).

Dr. Bachmann’s research interests include evaluation and validation of new clinical laboratory assays, clinical laboratory analyzer design, development of mass spectrometry-based assays for the clinical laboratory and standardization of laboratory testing. She serves as the Chair of the National Kidney Disease Education Program (NKDEP)/International Federation of Clinical Chemistry Laboratory (IFCC) Joint Lab Working Group, whose goal is to accomplish standardization of urine albumin methods to enable utility of clinical decision thresholds.

Dr. Bachmann has received numerous awards for her contributions to professional societies, education and research. She serves as principal investigator for multiple industry-sponsored studies.

Accurate 25-OH Vitamin D measurements are important for assessment and management of patients with hypovitaminosis D. LC-MS/MS measurement procedures are more selective than immunoassay measurement procedures for 25-OH Vitamin D and generally exhibit improved recovery of 25-OH Vitamin D2. However, challenges related to increased labor requirements for preanalytical processing, additional method validation requirements for LDTs and lack of complete automation of quality assurance monitoring have presented significant barriers for implementation of LC-MS/MS in the routine clinical laboratory. Hear from a clinical laboratory and LC-MS/MS expert about the quality assurance needs of the routine clinical laboratory, the challenges associated with managing laboratory developed tests (LDTs) and the perspectives on future LC-MS/MS developments.

*Thermo Fisher Scientific products are distributed globally so uses, applications, and availability of product in each country depend on local regulatory marketing authorization status.

Dr. Yu Xia earned her B.S. (1999) in Chemistry from Lanzhou University, China, M.S.
(2002) from Shanghai Institute of Material Medical, CASs, China, and Ph.D. (2006)
under the supervision of Professor Scott A. McLuckey from Purdue University, USA.
After postdoctoral training with Prof. Graham R. Cooks at Purdue, Dr. Xia took positions
as Assistant Professor and Associate Professor at the Department of Chemistry, Purdue
University. She is currently a Professor at the Department of Chemistry, Tsinghua
University, Beijing, China. Dr. Xia utilizes radical reactions as a unique approach to
achieve enhanced bioanalysis via mass spectrometry. In particular, her recent research emphasizes on
developing lipidomic tools capable of resolving structural isomers. Her work has resulted in over 90 peer-
reviewed publications and book chapters. Dr. Xia received ASMS Research Award (2013) and served as
Secretary of ASMS from 2015-2017. She is currently on the editorial board of the Journal of the American
Society of Mass Spectrometry.
Representative Publications:
1. X. Zhao, W. Zhang, D. Zhang, X. Liu, W. Cao, Q. Chen, Z. Ouyang, Y. Xia * , “A Lipidomic
Workflow Capable of Resolving sn- and C=C Location Isomers of Phosphatidylcholines”, Chem.
Sci., 2019, 10, 10740-10748
2. X. Xie, Y. Xia* “Analysis of Conjugated Fatty Acid Isomers by the Paternò-Büchi Reaction and
Trapped Ion Mobility Mass Spectrometry”, Anal. Chem. 2019, 91, 7173-7180.
3. W. Zhang, D. Zhang, Q. Chen, J. Wu, Z. Ouyang*, Y. Xia* “Online photochemical derivatization
enables comprehensive mass spectrometric analysis of unsaturated phospholipid isomers” Nat.
Commun., 2019, 10, 79-07963
4. X. Ma, L. Chong, R. Tian, R. Shi, T. Y. Hu, Z. Ouyang*, Y. Xia*, “Identification and quantitation
of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction”,
Proc. Natl. Acad. Sci. USA, 2016, 113, 2573-2578.
5. X. Ma and Y. Xia*, “Pinpointing Double Bonds in Lipids by Paternò–Büchi Reactions and Mass
Spectrometry”, Angew. Chem., Int. Ed , 2014, 53, 2592-2596.

Join the FeMS network (Females in Mass Spectrometry) for a presentation from special guest Dr. Yu Xia including time for discussion and a breakout networking session. This is a fun, informal way to stay connected and meet people in the field.

All are encouraged to join!

Follow FeMS on Twitter: @FemalesMassSpec
Join the FeMS LinkedIn Group.

Dr. Rosano is board certified in forensic toxicology by the American Board of Forensic Toxicologists and in clinical chemistry by the American Board of Clinical Chemistry. For over 35 years Dr. Rosano has been director of Clinical Chemistry and Toxicology at the Albany Medical Center Hospital where in 1993 he expanded toxicology services to include postmortem toxicology services for a 22 county region. During his career at the Albany Medical Center Dr. Rosano has progressed to tenured professor of Laboratory Medicine at the Albany Medical College where he has lectured and mentored medical and graduate students along with residents and fellows. In 2018 Dr. Rosano transitioned to toxicologist and director of the National Toxicology Center at the Center for Medical Science in Albany, New York and was promoted to Professor Emeritus in Laboratory Medicine at the Albany Medical College. His current focus is on court-ordered and addiction medicine casework and the advancement of clinical and forensic toxicology through innovations in high-volume definitive screening and applications of high-resolution mass spectroscopy.

Advancing analytical technology serves as the foundation of our toxicology practice and the explosion in pharmaceutical and illicit drug use now mandates the application of definitive testing technology in both our screening and confirmatory test protocols. While nominal mass GC-MS traditionally served as the analytical technology for confirmatory drug testing, the transition to liquid chromatography coupled with tandem mass spectroscopy has largely occurred and has brought with it an emerging application of high resolution mass spectroscopy. As definitive methods further the molecular identification and certainty of drug and metabolite confirmation work, our screening protocols in many areas of clinical toxicology still rely on presumptive methods with their high false negative rates and lack of selectivity. Conversion to definitive methods of screening with expanded drug panels is clearly needed but the challenges of high-volume screening with mass spectrometry has slowed the conversion to definitive screening across many areas of clinical toxicology. The hurdles on the way to definitive screening include automated sample preparation, rapid chromatography separation, analyte-specific matrix normalization, data management, alternative confirmatory methodology and interpretive reporting of findings. The presentation will focus on one laboratory’s journey and experience with definitive screening and confirmation protocols using a novel calibration technique for matrix normalization and application of high resolution mass spectroscopy for confirmation testing. Findings in addiction medicine and pain management casework will be presented and compared with the authors experience in court-ordered and postmortem casework.

Application of High-Resolution UPLC–MSE/TOF Confirmation in Forensic Urine Drug Screening by UPLC–MS/MS
Journal of Analytical Toxicology, 2019;43:353–363

Screening with Quantification for 64 Drugsand Metabolites in Human Urine using UPLC–MS-MS Analysis and a Threshold Accurate Calibration
Journal of Analytical Toxicology, 2017;41:536–546

Definitive Drug and Metabolite Screening in Urine by UPLC–MS-MS Using a Novel Calibration Technique
Journal of Analytical Toxicology, 2016;40:628–638

John R. Yates is the Ernest W. Hahn Professor in the Departments of Molecular Medicine and Neurobiology at The Scripps Research Institute. His research interests include development of integrated methods for tandem mass spectrometry analysis of protein mixtures, bioinformatics using mass spectrometry data, and biological studies involving proteomics. He is the lead inventor of the SEQUEST software for correlating tandem mass spectrometry data to sequences in the database and developer of the shotgun proteomics technique for the analysis of protein mixtures. His laboratory has developed the use of proteomic techniques to analyze protein complexes, posttranslational modifications, organelles and quantitative analysis of protein expression for the discovery of new biology. Many proteomic approaches developed by Yates have become a national and international resource to many investigators in the scientific community. He has received the American Society for Mass Spectrometry research award, the Pehr Edman Award in Protein Chemistry, the American Society for Mass Spectrometry Biemann Medal, the HUPO Distinguished Achievement Award in Proteomics, Herbert Sober Award from the ASBMB, and the Christian Anfinsen Award from The Protein Society, the 2015 ACS’s Analytical Chemistry award, 2015 The Ralph N. Adams Award in Bioanalytical Chemistry, the 2018 Thomson Medal from the International Mass Spectrometry Society, and the 2019 John B. Fenn Distinguished Contribution to Mass Spectrometry award from the ASMS. He was ranked by Citation Impact, Science Watch as one of the Top 100 Chemists for the decade, 2000-2010. He was #1 on a List of Most Influential in Analytical Chemistry compiled by The Analytical Scientist 10/30/2013 and is on the List Of Most Highly Influential Biomedical Researchers, 1996-2011, European J. Clinical Investigation 2013, 43, 1339-1365 and the Thomson Reuters 2015 List of Highly Cited Scientists. He has published over 950 scientific articles with >125,000 citations, and an H index of 174 (Google Scholar). Dr. Yates served as an Associate Editor at Analytical Chemistry for 15 years and is currently the Editor in Chief at the Journal of Proteome Research.

Developments in mass spectrometers over the last decade have been numerous, but there are some clear trends. The drive to increase confidence in the identification of peptides and post-translational modifications pushed the development of high-resolution and high-mass accuracy instruments, most notably Orbitrap and time-of-flight (TOF) mass analyzers. Improvements in mass resolution in these instruments resulted in an increase in the mass range for effective analysis, precipitating greater interest in the “top down” proteomics which now could be performed without expensive high-field magnets previously required for ion cyclotron resonance MS of intact proteins. Additionally, the emergence of biological therapeutics has fueled a greater need to characterize intact proteins to verify structure, sequence, and modifications. Fragmentation of the amide bonds in intact proteins requires more robust methods than fragmentation of peptides to obtain sequence information. Two methods in particular—electron transfer dissociation (ETD) and ultraviolet photodissociation (UVPD)—have been used to achieve more efficient fragmentation of intact proteins, especially when used in combination. These substantial improvements in MS capability have led to greatly improved prospects for top-down MS.

Karen holds an MBA from the Yale University School of Management and is founder and principal at Articulate Consulting. Karen has provided training in presentation development skills to professionals around the world from executives and managers to analysts, consultants, and graduate students. In addition, over her career as both a management consultant and a marketing professional for a Fortune 20 company, Karen has created a multitude of clear and compelling presentations to help senior executives and board members of large companies make better strategic decisions. She understands first-hand the challenges of creating presentations when the stakes are high and clients' expectations are even higher. Karen's style is both visionary and practical. She seeks to inspire others to have confidence in what they can accomplish with their presentations, and also to give them the concrete know-how and tools they need to immediately begin creating presentations that give them the influence they desire.

This is a one hour primer packed with actionable steps that will have a positive impact on how you communicate your science in presentations.

Karen will discuss aspects of Story Boarding, Visual Design, and Oral Delivery.

Several aspects of Karens full-length course will be covered, pulling from:

1. Storyboarding
Learn how to use storyboarding—the method used by the world’s largest management consulting firms and Fortune 500 companies—to structure your content so it's highly compelling.

2. Visual Design
Visual polish goes a long way in establishing the credibility of your ideas. Learn to design visually appealing, professional-looking slides—whether you consider yourself artistically inclined or not!

3. Oral Delivery
Discover the secrets to delivering your presentation in a way that fully engages your audience with your ideas so they leave energized and ready to take the next steps you want them to.

More specific Learner Objective coming soon.

Theodore Alexandrov is a group leader at the European Molecular Biology Laboratory (EMBL) in Heidelberg, the head of the EMBL Metabolomics Core Facility and an Assistant Adjunct Professor at the Skaggs School of Pharmacy, University of California San Diego. The Alexandrov team at EMBL aims to reveal secrets of metabolism in time and space in tissues and single cells by developing experimental and computational methods. The team unites interdisciplinary scientists from biology, chemistry, and computer science as well as software and machine learning engineers. Theodore Alexandrov is a grantee of an ERC Consolidator project focused on studying metabolism in single cells, as well as of various other European, national, NIH, and industrially-funded projects. He has co-founded and scientifically directed the company SCiLS and has over 70 journal publications and patents in spatial omics.

PhD 2007, St. Petersburg State University, Russia
Postdoctoral research at the University of Bremen, Germany
Group leader, University of Bremen, Germany
Assistant Adjunct Professor, University of California San Diego, USA
Team leader at EMBL since 2014.

The METASPACE platform hosts an engine for metabolite annotation of imaging mass spectrometry data as well as a spatial metabolite knowledgebase of the metabolites from hundreds of public datasets provided by the community.

An overview of the fundamentals that are driving research and development in the field of Lipidomics.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.

Learning objectives include:

1. Be able to define what Lipidomics is, why it matters, and why you personally should care. What is the clinical relevance?
2. Understand what role mass spectrometry plays in this field. Where does mass spec fit in to the big picture of the field?
3. Define any terminology that is specific to this field.
4. Describe how it works, what are the methods and workflows used when studying this field and/or how is it implemented in clinical labs.
5. Identify any challenges to implementation/adoption, where do the opportunities lie?

Bachelor Degree in Chemistry obtained from NC State University in Raleigh, North Carolina, with early research experience in Molecular Paleontology under the mentorship of Dr. Mary H. Schweitzer analyzing soft tissue extracts from a 66 million year old T. rex specimen. This early research experience inspired a passion for analytical sciences.

Upon Completion of B.S. Degree in 2006, continued Graduate School at NC State with a focus in Bioanalytical Chemistry and a Graduate Minor in Biotechnology under the mentorship of Dr. David Muddiman at the W. M. Keck FT-ICR Mass Spectrometry Laboratory, working on biological systems ranging from fungal crop pathogens to human embryonic stem cell biology, with methodological focuses on quantitative Top-Down and Bottom-Up Proteomic Methodologies. This exposure to applying new analytical methods to pursue questions related to human health inspired a decision to pursue research in that area further.

After completion of Ph.D. work in 2010, training continued as a Post-Doctoral Research Scholar in the division of Molecular Oncology at Washington University School of Medicine in St. Louis, MO, in the lab of Dr. Ron Bose, and with additional mentorship from Dr. Michael Gross, where quantitative proteomic and siRNA methods were developed to identify drug-resistance mechanisms in HER2 positive breast cancers. Further structural mass spectrometry methods were combined with molecular dynamics simulations to identify specific multimeric interactions between HER2 and HER3 kinases to illuminate structural relationships between tumor-driving mutations and unregulated signaling activity.

Upon completing post-doctoral work in 2013, moved to Cleveland, OH to become a Research and Development Scientist at Cleveland HeartLab, Inc., working with a dynamic team to develop diagnostic tests based on novel biomarkers to improve assessment of cardiovascular risk, and was promoted to current role Senior Research and Development Scientist in 2016.

An overview of the fundamentals that are driving research and development in the field of Proteomics.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.

Learning objectives include:
1. Be able to define what Proteomics is, why it matters, and why you personally should care. What is the clinical relevance?
2. Understand what role mass spectrometry plays in this field. Where does mass spec fit in to the big picture of the field?
3. Define any terminology that is specific to this field.
4. Describe how it works, what are the methods and workflows used when studying this field and/or how is it implemented in clinical labs.
5. Identify any challenges to implementation/adoption, where do the opportunities lie?

- B.S. in Biochemistry and Molecular Biology, Centre College, 1986

- Ph.D. in Biochemistry and Molecular Biology, University of Kentucky,1990

- Post-doctoral Fellow, Department of Biochemistry, University of Texas Health Science Center at San Antonio with Alan Elbein, 1990-1992

- Assistant/Associate Professor, Department of Biochemistry, University of Arkansas for Medical Sciences, 1992-2001

- Associate/Full Professor, Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 2001-2011

- Professor, Department of Cell and Molecular Pharmacology, Medical University of South Carolina, 2011-present

An overview of the fundamentals that are driving research and development in the field of Glycomics.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.

Learning objectives include:
1. Be able to define what Glycomics is, why it matters, and why you personally should care. What is the clinical relevance?
2. Understand what role mass spectrometry plays in this field. Where does mass spec fit in to the big picture of the field?
3. Define any terminology that is specific to this field.
4. Describe how it works, what are the methods and workflows used when studying this field and/or how is it implemented in clinical labs.
5. Identify any challenges to implementation/adoption, where do the opportunities lie?

Dr. Joe El-Khoury is Assistant Professor of Laboratory Medicine at Yale School of Medicine, Director of the Clinical Chemistry Lab and Co-Director of the Clinical Chemistry Fellowship program at Yale-New Haven Health. He is board certified by the American Board of Clinical Chemistry (ABCC) and a fellow of the AACC Academy. He currently serves on the Board of Directors of CLMA, as well as the SYCL Core Committee, IFCC Task Force for Young Scientists and as Chair of the AACC NY Metro Section. His research interests are pre-analytical errors, biomarkers of kidney disease, and liquid chromatography-mass spectrometry in the clinical laboratory.

This informal Practical Training session will include a presentation on Financial Considerations for Purchasing a Mass Spectrometer, as well as offer small group discussion and networking opportunities.

1. Describe the clinical and monetary benefits of purchasing a mass spectrometry system.
2. Identify different models for financing a mass spectrometry system purchase.
3. Participate in effective negotiations with vendors.

Alan Rockwood, PhD, DABCC is Professor (Clinical) Emeritus of Pathology at the University of Utah School of Medicine in Salt Lake City, Utah, USA. Originally trained in Physical Chemistry, he performed research on the fundamentals of mass spectrometry and instrumentation development before focusing his career on Clinical Chemistry. He is certified by the American Board of Clinical Chemistry and has held a Certificate of Qualification in Clinical Chemistry from the New York State Board of Health. Currently, his primary area of research is the development of mass spectrometry-based quantitative assays for targeted analytes of clinical interest, including small molecules and more recently proteins and peptides. Additionally, he maintains a smaller research effort on fundamentals of mass spectrometry, particularly novel approaches for isotopic profile calculations. He has published >150 papers in peer reviewed journals.

Join us for an award presentation presented by the Distinguished Contribution Award Committee, followed by a plenary presentation from the awardee.

Judy Stone, MT (ASCP), PhD, DABCC has worked with LC-MS in diagnostic laboratories since 1999. Her clinical practice involved small molecule method development, instrument to instrument and instrument to LIS interfacing, LC-MS automation, monitoring quality of LC-MS methods in production and staff training for clinical LC-MSMS. She served as faculty chair for the 2009 AACC online certificate program “Using Mass Spectrometry in the Clinical Laboratory”, as a scientific committee member for the MSACL Practical Training track, and is editor-in-chief for the AACC Clinical Laboratory News quarterly feature series on Clinical LC-MS. She enjoys documenting and presenting esoteric as well as absurdly common LC-MS problems in creative ways in order to help trainees learn troubleshooting (and avoid repeating her mistakes).

Grace is an LC-MS/MS Applications Development Specialist at St Paul’s Hospital in Vancouver BC. She is passionate about developing the most user friendly and streamlined LC-MS/MS assays as possible for routine use in the Special Chemistry Mass Spec Lab. She loves troubleshooting, especially when the cause of problem has been discovered and the issue solved!

Deborah French Ph.D., DABCC (CC, TC) is currently Assistant Director of Chemistry and Director of Mass Spectrometry at the University of California San Francisco Clinical Laboratories. Her work currently focuses on the development and validation of LC-MS/MS assays for small molecules, specifically therapeutic drug monitoring, steroid hormones and toxicology. Deborah received her Ph.D. in biochemistry from the University of Strathclyde in Glasgow, Scotland and then completed a postdoctoral fellowship at St. Jude Children’s Research Hospital in Memphis, TN. She subsequently completed a ComACC Clinical Chemistry postdoctoral fellowship under the direction of Dr Alan Wu at the University of California San Francisco and is now board certified in Clinical Chemistry and Toxicological Chemistry by the American Board of Clinical Chemistry.

Download Schedule

New Online Format

This is a virtual version of the short course that has been presented at MSACL. This online course includes 4 hours of live lecture each day for four days. Using Zoom (live online lectures, breakout rooms for interactive sessions) and Google Classroom (forms and job aids for download, on demand short lecture videos) provides additional opportunities for interactive and self-paced learning, both during the four-day course and beyond.

The resources posted in Google Classroom will be available to registrants until December 31, 2020. We can’t give you hands-on experience with cutting PEEK tubing or changing check valves in an online course. But the potential with a virtual platform for networking and updates with actionable information to help you with your daily LC-MS/MS clinical practice seems almost limitless.


Course Content Description

Is your laboratory under pressure to purchase an LC-tandem MS or is the ROI you wrote last year haunting you now? This short course is designed for attendees implementing quantitative LC-tandem MS for patient testing who have laboratory medicine experience but no mass spectrometry training - CLS bench analysts, supervisors, R&D scientists, and laboratory directors. Theoretical concepts necessary for a robust implementation of clinical mass spectrometry will be presented – but the emphasis is on practical recommendations for:

1. LC-MS/MS system purchasing
2. site preparation and installation
3. defining preliminary MSMS and LC parameters for your first method
4. selecting and optimizing sample preparation for your first method
5. choosing internal standards, solvents, and water, making reagents and calibrators
6. adjusting sample preparation, LC and MSMS parameters to achieve the desired assay performance
7. establishing data analysis & batch review criteria
8. pre-validation stress testing and method validation
9. preventative maintenance and troubleshooting
10. maintaining quality in production.

Our goal is to present just enough theory so you can report high quality results, while opening a window to the depth and complexity of clinical mass spectrometry such that your appetite is whetted to learn more. The IFCC Committee for Distance Learning published a curriculum guideline for post-graduate trainees in laboratory medicine in 2017. This course includes all of the IFCC mass spectrometry curriculum listed in the “Principles of Analysis X-MS” section, except that we focus only on triple quadrupole mass spectrometry; metabolomics, proteomics and inborn errors of metabolism are not discussed. See also this reference by one of the team of short course instructors “Liquid chromatography-mass spectrometry education for clinical laboratory scientists”.

Previous exposure to the principles of clinical method validation, either didactic or practical, is assumed. A post-course online exam will be available, with a certificate of completion for those who take and pass the exam within the examination window of two weeks after the four day short course.

An overview of the fundamentals that are driving research and development in the field of Data Science.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.

Learning objectives include:
1. Be able to define what Data Science is, why it matters, and why you personally should care. What is the clinical relevance?
2. Define any terminology that is specific to this field.
3. Describe how it works, what are the methods and workflows used when studying this field and/or how is it implemented in clinical labs.
4. Identify any challenges to implementation/adoption, where do the opportunities lie?

Medical School
MD - Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA

Residency
Clinical Pathology - Massachusetts General Hospital, Boston, MA (Chief Resident)

Fellowship
Transfusion Medicine - Harvard Medical School, Cambridge, MA

Board Certification
Clinical Pathology

Graduate Degree
PhD in Cell and Molecular Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA

Michael Kane is an Assistant Professor in Yale University's Biostatistics Department. He is interested in Scalable Statistical/Machine Learning, Statistical Computing, and Applied Probability.

Joseph is RStudio’s “Ambassador at Large” for all things R, editor of the R Views blog, and RStudio’s representative on the R Consortium’s board of directors. Joseph came to RStudio via Revolution Analytics and Microsoft where he was a data scientist, blogger and community manager. Before joining Revolution Analytics Joseph worked as a statistician for a small healthcare economics consulting firm, and before that he held a variety of technical, marketing and sales positions while working for startups that spanned multiple industries including government contracting, local area networks, disk drives and test equipment. Joseph studied Classics and Mathematics as an undergraduate at Franklin & Marshall College and earned an M.A. in Humanities and an M.S. in Statistics from the California State University.

EDUCATION:
Graduate School: University of Virginia (Chemistry), Charlottesville, VA
Clinical Chemistry and Laboratory Medicine Fellowship: University of Virginia, Charlottesville, VA

CLINICAL:
Laboratory testing in Clinical Chemistry, Toxicology, Hemostasis, and Endocrinology.

RESEARCH:
Liquid chromatography mass spectrometry assay methods.

My lab performs research and clinical testing using mass spectrometry methods, develops new assays, and applies data analytics to enable improved quality and efficiency. My computational pathology efforts are aimed at building the capacity for advanced data analytics in the department through innovations in infrastructure, education, and research to facilitate data-informed decision making for clinical care, operations, and quality assurance.

R is a freely available open-source programming language and a powerful statistical computing environment that is extremely popular among statisticians and data scientists. R is ideally suited for building customized applications for clinical operations, however many (real and perceived) hurdles exist in operationalizing R in healthcare in general, and in the labs in particular. This session is hosted by the organizers of R/Medicine, an annual conference aiming to promote the R ecosystem in clinical research and practice. This will be a highly interactive session aimed to share insights and experiences both of the discussants and participants, with the aim of facilitating the integration of the R ecosystem into clinical laboratory practice.

Hosted by R/Medicine

Panelists:

Stephan Kadauke, Assistant Professor of Pathology and Laboratory Medicine at the Children’s Hospital of Philadelphia, Chair of R/Medicine 2020

Michael Kane, Assistant Professor of Biostatistics at Yale University School of Public Health, past Chair of R/Medicine

Joseph Rickert, R Consortium, and RStudio, PBC

Lindsay Bazydlo, Associate Clinical Professor of Pathology, University of Virginia

Shannon Haymond, Associate Professor of Pathology, NorthWestern University

After completing this activity, participants will be able to:

1. Cite resources available for R and data science education tailored for clinicians and laboratorians.

2. Describe organizational, regulatory, and cultural challenges to integrating the R ecosystem into clinical practice.

3. Discuss best practices for building customized clinical laboratory-developed applications (“lab apps”) in R/Shiny.

Nina Ogrinc finished her PhD at the University of Ljubljana, and the Department of Low and Medium energy Physics, at Jozef Stefan Institute, Slovenia.
In 2014, she joined the group of Prof. Ron Heeren (M4I) in Maastricht, Netherlands as a postdoctoral researcher. During this time, she was involved in the Marie Curie BRAINPATH consortium and actively engaged in a variety of projects developing and applying new mass spectrometry imaging tools for biomarker discovery (lipids, metabolites, peptides) in neurodegenerative diseases
Since October 2018 she is working at laboratory PRISM (Inserm U1192, University of Lille), under the direction of Prof Michel Salzet and Prof. Isabelle Fournier, on a highly innovative SpiderMass project, an instrument designed for guided surgery and real-time diagnosis in the surgical operating room. She is currently developing a multimodal platform for mass spectrometry and imaging techniques which will enable complex, low cost, rapid, molecular profiling for faster cancer diagnostics and biomarker discovery.

Paula M. Ladwig, M.S., MT (ASCP), is a Development Technologist Coordinator with the Clinical Mass Spectrometry Development Laboratory, Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, MN. She has over 10 years of experience in the development and validation of new mass spectrometry tests. Her interests include the implementation of therapeutic drug monitoring of monoclonal antibody therapeutics by mass spectrometry.

Session Overview

The clinical laboratory will have many roles as monoclonal antibody therapeutics (t-mAbs) expand: identifying potential interferences in routine immunoassays; developing new assays to differentiate a t-mAb from an endogenous, disease-causing plasma cell clone and monitoring therapeutic drugs for better patient outcomes and assessing loss of response to therapy. This session will provide an overview of mass spec techniques available to the clinical laboratory for t-mAb detection and quantitation along with their advantages and disadvantages. Finally this session will offer a few examples of hurdles in the implementation into the clinical laboratory setting.

Target Audience

This session is intended for clinical laboratory directors and pathologists, clinical technologists, IVD manufacturers, pharmaceutical scientists, and anyone interested in the mass spectrometry applications for therapeutic monoclonal antibodies especially those involved in development of new methods for t-mAb monitoring.

Needs Assessment

There are over 60 different therapeutic monoclonal antibodies (t-mAbs) approved by the FDA; used to treat a variety of diseases. The market for monoclonal antibodies is rapidly growing, with over 500 new t-mAbs in several stages of development. Laboratorians are quite familiar with the detection, screening, and quantitative therapeutic drug monitoring for small molecules as the methodologies have been well established, therapeutic ranges for many drugs have been defined, and the metabolic pathways for many small molecules have been elucidated in detail. However, this is not the case for the t-mAbs. The detection, screening, and quantitative measurement of these monoclonal antibodies require different technologies.

Mass spectrometry is an important tool in the field of t-mAbs; mostly because it is relatively simple and so versatile once you understand how to apply the basic principles, challenges and limitations of each different approach and instrumentation. This session will provide examples of approaches for mass spectrometry assay development for chimeric, humanized and fully human t-mAbs quantitation; from peptide by quadrupole MS to intact or subunit detection by time-of-flight or orbitrap MS.

Following the completion of this session, the participant will be able to:

1. Describe mass spectrometry techniques available for the assessment of monoclonal antibody therapeutics along with their advantages and disadvantages.

2. Discuss screening and quantitation approaches.

3. Describe common hurdles and how to avoid them.

Judy Stone, MT (ASCP), PhD, DABCC has worked with LC-MS in diagnostic laboratories since 1999. Her clinical practice involved small molecule method development, instrument to instrument and instrument to LIS interfacing, LC-MS automation, monitoring quality of LC-MS methods in production and staff training for clinical LC-MSMS. She served as faculty chair for the 2009 AACC online certificate program “Using Mass Spectrometry in the Clinical Laboratory”, as a scientific committee member for the MSACL Practical Training track, and is editor-in-chief for the AACC Clinical Laboratory News quarterly feature series on Clinical LC-MS. She enjoys documenting and presenting esoteric as well as absurdly common LC-MS problems in creative ways in order to help trainees learn troubleshooting (and avoid repeating her mistakes).

Nicholas Laude is a Senior Scientist and the Technical Supervisor of the Clinical Toxicology Laboratory at Genotox Laboratories, LTD in Austin,TX. After completing his Ph.D. in Analytical Chemistry at The University of Arizona, he began using his Mass Spectrometry expertise in a clinical setting. Currently he specializes in LC-MS/MS applications for toxicology using triple quadrupole and ion trap mass spectrometers. Additionally his work includes the use of MALDI-TOF systems for Molecular Diagnostic applications, particularly in DNA-Authentication of clinical samples.

Douglas Toal, Ph.D., D(ABMM) is the Clinical Laboratory Director at Metabolon, Inc. (Morrisville, NC) where he works with other scientists to pioneer the clinical application of metabolomics for the screening of inborn errors of metabolism and undiagnosed disease. His teams have developed and validated novel small molecule assays for prediabetes and chronic kidney disease. He completed postdoctoral-fellowship training at the Mayo Clinic (Rochester, MN) and has served as Laboratory Director for clinical reference laboratories and CRO’s. He has over twenty-five years of experience in translational research, clinical laboratory operations and assay development.

Dr Kim Ekroos is the founder and CEO of Lipidomics Consulting Ltd. He received his Ph.D. degree in biology from the Technical University in Dresden, Germany, in 2003. His expertise includes high-throughput technologies for the precise assessment of lipidomes enabled by advanced mass spectrometry, automation, and software tools towards discovery of biological architectures and of diagnostic biomarkers for clinical purpose. He is one of the pioneers in the field of lipidomics, with more than 20 years of experience in the academic, industry and regulatory disciplines of lipidomics. He is a co-founder of the Lipidomics Standards Initiative (LSI) and the president of the International Lipidomics Society.

Jessica Lukowski is currently a spatial metabolomics postdoctoral researcher at Pacific Northwest National Laboratory working under the direction of Dr. Christopher Anderton. She received her BS in chemistry from Butler University in 2014. She continued her education by joining Dr. Amanda Hummon’s laboratory at the University of Notre Dame and earned her PhD in analytical chemistry in 2019.

Sankha (Bobby) Basu, MD, PhD received his BS in Biology and Chemical Engineering in 2003 at MIT and obtained his MD and PhD (Pharmacology) degrees in 2013 from the University of Pennsylvania School of Medicine. His thesis work involved the development and application of stable isotope LC-MS/MS methods to study mitochondrial disease, which was conducted in the laboratory of Dr. Ian Blair. He then went back to Boston to complete a residency in Clinical Pathology and a fellowship in Medical Microbiology at the Brigham and Women's Hospital (BWH). Following his clinical training, he joined the laboratory of Dr. Nathalie Agar at BWH as a post-doctoral research fellow working on a variety of applications including intraoperative MS and MALDI MSI. He recently joined the faculty at BWH as Assistant Director of Clinical Chemistry and Mass Spectrometry and Instructor of Pathology at Harvard Medical School. His clinical roles include the development and implementation of LC-MS methods in clinical chemistry and MALDI TOF based microbial identification in microbiology. Additionally, he continues his work with the Agar lab on clinical and translational applications of MS.

Kyana Garza graduated from the University of St. Thomas in Houston in 2016 with a B.S. in Chemistry. She is currently a fourth-year graduate student at the University of Texas at Austin and works under the supervision of Prof. Livia S. Eberlin. Kyana has worked on several projects that focus on developing and applying mass spectrometry techniques for enhanced and expedited breast cancer diagnosis, with the goal being to improve patient management and outcome.

Richard B. van Breemen is the Linus Pauling Endowed Chair of Pharmaceutical Sciences and Director of the Linus Pauling Institute at Oregon State University. Prof. van Breemen received his B.A. in chemistry from Oberlin College and Ph.D. in Pharmacology and Experimental Therapeutics with Catherine Fenselau from the Johns Hopkins University. He carried out post-doctoral research in laser desorption mass spectrometry with Robert Cotter at Johns Hopkins. His research concerns biomedical mass spectrometry applied to natural products, chemoprevention, drug metabolism, natural product-drug interactions, and toxicology.

In her former role as an associate professor at the University of Toronto, Amy Caudy was a principal investigator in the Stand Up to Cancer Canada Brain Tumor Stem Cell Dream Team where she directed full scan metabolomics of clinical samples as part of a multi-omics study. She is now managing operations at Maple Flavored Solutions LLC, a provider of mass spectrometry analysis and consulting.

Evgeny Berdyshev is an Associate Professor at National Jewish Health in Denver, CO where he leads mass spectrometric laboratory and the Core. He is a lipid biochemist with a long-standing interest in analytics of lipid signaling molecules and in lipid mass spectrometry. Dr. Berdyshev special focus during last five years is in the area of skin sphingolipidomics/metabolomics and understanding the role of lipids in atopic skin diseases and how they can be used to discriminate subphenotypes of atopic dermatitis or evaluate the efficacy of therapeutic interventions.

Our laboratory is specialized on mass spectrometric approaches to study the involvement of lipid signaling molecules in the development of different pulmonary diseases. Our main current focus is at sphingolipid signaling molecules as the inducers and modulators of COPD and pulmonary fibrosis. In particular, we have established an important link between sphingolipid de novo biosynthesis and the development of emphysema. We also investigate how natural, synthetic, and endogenous ligands for cannabinoid receptors affect fibrotic processes in the lung. Another focus area for our group is the involvement of polyunsaturated molecular species of lysophosphatidic acids in the allergic responses in the lung. We try to understand metabolic pathways involved and sources of lysophosphatidic acid production in the lung and to link lysophosphatidic acid generation to the severity and subtypes of asthma.

I currently work as a Chemistry Informatics Specialist for the Department of Laboratory Medicine at the University of Washington under Patrick Mathias. I help build and support efficiency improvements and automation for our mass spectrometry assays performed in the chemistry division. I previously worked in mass spectrometry method development and clinical testing at the Johns Hopkins University.

Dr. Benjamin Owusu is a Senior Clinical Chemistry Fellow at the University of Washington School of Medicine. Benjamin received his PhD degree in Biochemistry and Molecular Genetics and went on to do a one-year postdoctoral research fellowship at the University of Alabama at Birmingham (UAB). He obtained his Bachelor of Science degree in Biochemistry at the University of Ghana, where he also served as a Teaching Assistant at the Department of Biochemistry upon completion of his undergraduate training. He later moved to Emory University School of Medicine in Atlanta, GA on a visiting research scholarship prior to starting his doctoral training at UAB. His research over the years span across cancer, cardiovascular, hematological and endocrinological diseases. In addition to clinical service and research, Benjamin is passionate about teaching and mentoring, particularly in STEM education.

Meng Wang is a postdoctoral research fellow at the University of British Columbia. Her work focuses specifically on the development, optimization, and validation of targeted mass spectrometry protein assays.

Stephen Roper is an Assistant Professor of Pathology and Immunology at Washington University of School of Medicine and the Assistant Director of Pediatric Laboratory Services at St. Louis Children's Hospital. He received his PhD in Biomedical Science from the Medical University of South Carolina in 2015, where his research focused on the identification of alternatively-sialylated glycoproteins in non-small cell lung cancer progression and imaging mass spectrometry with Richard Drake, PhD. Following the completion of graduate school, Stephen began his postdoctoral training in clinical chemistry at Baylor College of Medicine and Texas Children's Hospital. His research interests include pediatric clinical chemistry, toxicology, and broadening the applications of LC-MS/MS in clinical laboratories.

Ethan Yang is a PhD candidate in Prof. Pierre Chaurand’s lab at the University of Montreal. His research primarily focuses on elaborating new techniques to enhance the sensitivity and selectivity of MALDI-TOF imaging mass spectrometry for use in fundamental and clinical research to better elucidate lipid biomarkers on thin tissue sections. He obtained his B.Sc. at McGill University, majoring in Biochemistry. Since 2012, he has been an active member of the Let’s Talk Science site in Montreal, a national non-profit organization focused on promoting interest in STEM (science, technology, engineering and mathematics) in youth.

Zoe is a lecturer in the Division of Systems Medicine, Imperial College London. Prior to this, she carried out her PhD at the University of Oxford and held post-doctoral appointments at the London School of Hygiene and Tropical Medicine and the University of Cambridge. Zoe’s research interests lie at the intersection of mass spectrometry imaging, lipid metabolism and spatial systems biology, with a focus on non-alcoholic fatty liver disease and cancer.

Andrew DelaCourt is a second-year Ph.D student in Dr. Anand Mehta's lab at the Medical University of South Carolina. His research project in Dr. Mehta's lab focuses on the study of glycan biomarkers for hepatocellular carcinoma. He received his undergraduate degree with honors in chemistry from Wake Forest University in 2018.

I am a research fellow at Department of Medicine, National University of Singapore. I work on the lipidomics of non-alcoholic fatty liver disease.

Peggi Angel is Assistant Professor in the Department of Pharmacology at the Medical University of South Carolina. Her research focuses on development and application of imaging mass spectrometry studies on human disease. She has developed novel IMS approaches to investigate phosphoinositol lipids and fatty acids, collagen type regulation in tissue sections, and N-glycosylation of single cell layers. Dr. Angel applies these approaches to understand fibrosis in heart, liver and cancer progression of breast, prostate and lung. Dr. Angel is a co-founder of Glycopath LLC, a company that focuses on glycosylation analysis as a prognostic or diagnostic tool. She serves on the board of N-Zyme Scientifics, a company that produces enzymes for mass spectrometry. Dr. Angel is committed to serving the imaging mass spectrometry community and serves on the Imaging Mass Spectrometry Society Executive Committee and the MSACL Scientific Committee.

Research Specialty: Proteomics analysis in development and disease; mass spectrometry technology development.

The Schey lab is interested in both method/instrument development in proteomics analysis as well as in applications of state-of-the-art proteomics technologies in the study of development and disease. Method development/technology projects include methods for integral membrane protein analysis, tandem mass spectrometry of intact proteins (top-down proteomics), spatially-resolved proteomics analysis, and quantitative proteomics. The major area of application is human lens protein modifications and protein-protein interactions. Other areas of interest are: proteomics analysis of heart valve development, and invertebrate (shrimp and oyster) innate immunity. Integral membrane proteins play key roles in signaling, transport, and adhesion, yet they remain difficult to analyze using conventional proteomics methods.

Our lab has developed methods to analyze integral membrane proteins and membrane associated proteins including their modifications. In addition, we have developed methods for membrane proteome analysis. Currently we are developing methods for spatially-resolved studies (see below), for tissue imaging of membrane proteins, and for examining the membrane protein phosphoproteome. Standard proteomics analyses typically require tryptic digestion of the protein sample followed by LC/MS/MS analysis of the peptides in order to identify and quantitate the proteins present in the sample. This bottom-up approach relies on inferring protein level information from peptide level measurements. Top-down analysis involves analysis of the intact proteins for identification but requires sophisticated technologies and software.

We have developed a method for top-down proteomics analysis in a MALDI TOF-TOF platform and generated a new software application for the interpretation of resulting data. Spatially-resolved proteomics represents a critically important area of development that takes advantage of recent advances in instrumental sensitivity. The ability to examine region-specific changes in a proteome has wide applicability in both development and disease processes. Two approaches are being developed in our lab to address this issue: 1) laser capture microsdissection (LCM) coupled with shotgun proteomics analysis and 2) MALDI tissue imaging. We have combined our membrane protein analysis protocols with LCM capture to examine region-specific changes in the ocular lens membrane proteome. Also, we have developed new sample preparation methods to allow MALDI imaging of membrane proteins. The MALDI imaging method is being applied to lens aging, chick and mouse heart development, shrimp viral infection, brain changes in addiction, and lung infection. Our long-standing project on ocular lens membrane proteins is focused on how these proteins change as lens cells differentiate and as they age. Since the proteins in the lens core are as old as the individual, the lens serves as a model tissue to study protein aging. Age- and cataract-specific modifications have been identified and regional changes in the membrane proteome are being examined. Functional consequences of lens protein modification are also being examined with confocal microscopic, molecular biology, and spectroscopic methods.

Holly Cox received her Ph.D. in Biochemistry from The Ohio State University. In 2010, she joined the Sports Medicine Research and Testing Laboratory (SMRTL). She has published methods for the measurement of IGF-1 and several banned peptides in athlete urine, serum, and dried blood spot samples. As the Senior Research Scientist, her research is focused on developing new methods to detect blood doping practices and abuse of erythropoiesis stimulating agents, human growth hormone, and insulin analogues.

Born in Ukraine. Obtained an MS degree there and came to the US for the graduate school. Graduated from Oregon State University with a Ph.D. in Chemistry. There I met my (then future) wife, with whom I moved around the country looking for a place to settle: Pittsburgh, Ithaca and finally Southern California. Favorite hobby: hiking and camping.

Dr. Surendra Dasari is an Associate Professor of Biomedical Informatics at the Mayo Clinic. He specializes in the development of analytical and informatics methods for new diagnostics. Dr. Dasari's efforts underlie the development and implementation of mass spec-based methods for amyloid typing and monoclonal gammopathy detection and isotyping. Dr. Dasari also has an active research base in cancer biology of t-cell lymphomas, insulin resistance, aging and renal diseases where he utilizes multi-omics to understand the pathobiology of diseases.

Natalicia de Jesus Antunes is a Brazilian Pharmacist. Currently, she is a Visiting Researcher at Queen Mary University of London, London under supervision of Professor Atholl Johnston. In Brazil, she is a Post-Doctoral researcher at the Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas - UNICAMP, Campinas. She studied Pharmacy at the Federal University of Alfenas, Brazil. Her master and doctoral studies were conducted at the Faculty of Pharmaceutical Sciences of Ribeirão Preto of the University of São Paulo, in Ribeirão Preto. Since her Master's, she has been working with bioanalyses using LC-MS/MS in Clinical Pharmacokinetic studies.

Gang Xu is currently a first-year clinical chemistry postdoctoral fellow in the Department of Pathology and Laboratory Medicine at Medical University of South Carolina. He received his B.E. in Pharmaceutical Engineering in 2007 at Xi`an University of Technology, M.S. in Chemistry in 2012 and Ph.D. in Clinical-Bioanalytical Chemistry in 2019 at Cleveland State University. During his PhD studies he has successfully completed several LC-MS/MS-related projects. His experience with development of LC-MS/MS-based assay spans five years and encompasses both targeted (small molecule quantitation) and untargeted analysis (biomarker studies using metabolomics or lipidomics) with oral or poster presentations in local and national conferences and several publications in peer-reviewed journals and prepared manuscripts pending submission.

Dr. Dubland completed his BSc in chemistry at Simon Fraser University, followed by an MSc in organic chemistry at the University of Toronto. He was then employed as a research associate in the pharmaceutical industry for 4 years, working at both BRI Biopharmaceutical Research Inc. and QLT Inc. Work in the pharmaceutical industry focused on bioanalytical mass spectrometry development, validation, and data acquisition to support clinical and preclinical drug trials. Following this, Dr. Dubland completed his PhD in Experimental Medicine at UBC where his research focused on cellular mechanisms of lipid accumulation and removal in atherosclerosis. Dr. Dubland is currently a Laboratory Scientist in the Newborn Screening and Biochemical Genetics Laboratories at BC Children’s Hospital.

Austin Pickens received his doctorate in Human Nutrition from Michigan State University, investigating biomarker discovery using targeted and untargeted high resolution mass spectrometry. He then joined a cancer informatics startup within the ORACLE Corporation as a data scientist. Austin joined the Biochemical Mass Spectrometry Laboratory (BMSL) at the Centers for Disease Control and Prevention in November 2017, where he develops methods, evaluates new technologies, and investigates metabolomics in newborn screening.

I have a PhD in Bioanalytical chemistry in proteomics and metabolomics from Memorial University of Newfoundland (NL, Canada). I worked in the Newborn Screening and Biochemical Genetics laboratory in the Department of Genetics at King Faisal University Hospital and Research Center (KFSHRC). I work on Clinical Metabolomics and leading a research-based activity to establish comprehensive metabolomics platforms for biochemical genetic diseases. The metabolomics platforms that we have established in our lab are readily used for Biomarker discovery.

Anna Krieger received her B.A. in Chemistry from Gustavus Adolphus College in Saint Peter, Minnesota in 2017. She is currently a graduate student in Prof. Livia S. Eberlin’s lab at the University of Texas at Austin. Her research is focused on developing the MasSpec Pen and other ambient ionization techniques for molecular characterization of brain cancers.

Emma is a graduate student at Vanderbilt University studying under Drs. Richard Caprioli and Jeffrey Spraggins. She finished her undergraduate studies at the University of Notre Dame in 2018 with degrees in Chemistry and Philosophy while working in the Warren Center for Drug Discovery. Her current work involves applying spatially-targeted mass spectrometry methods to better understand host-pathogen interactions in infectious diseases, especially those in the gastrointestinal tract.

Professor Michel salzet (Distinguish Professor) Is a member of the Institut Universitaire de France in the speciality of immunoproteomic. He is director of the unit, UMR 1192 Inserm. He discovered with Professor Xavier Roucou, the ghost proteins through proteomic approaches combined with Bioinformatic analyses. For this achievement, they received the Quebec science Award for the discovery of the year 2014. Professor Michel Salzet has (co-)authored more than 335 papers (H-index 58, google scholar) and he has published in Top notch journals like Cancer Cells, Nature protocols, Nature Immunology, Circulation, Blood, Trends in immunology.

Innovative mass spectrometry-based analytical methods and sample preparation designs that are transferable to other analytical laboratories. Modulations in hormone biosynthesis and metabolism from consumption of botanical dietary supplements. Metabolism and pharmacokinetics of small molecules. Design of data-mining strategies for efficient metabolite identification.

Andrew Reckers is a Staff Research Associate at the University of California San Francisco. He has industry and academic LCMS experience working with anti-TB drug detection in hair, environmental biomonitoring in human and food samples, and identifying novel psychoactive substances in overdose patients.

EU Marie Curie Actions Global Fellow based at the University of Birmingham and ANZAC Research Institute, University of Sydney.

Dr. Chia-Ni Lin joined Chang Gung Memorial Hospital in 2012. She received her Ph.D. degree in Clinical Laboratory Sciences and Medical Biotechnology from National Taiwan University in Taiwan followed by a fellowship in Clinical Chemistry at ARUP/University of Utah. She is board certificated by the American Board of Clinical Chemistry (ABCC) and a fellow of AACC academy. Her research interests are development, method improvement and validation of clinical laboratory assays, and mass spectrometry applications in clinical laboratory including metabolites in biological fluids, illicit drugs, trace elements and hormones.

He is a Research Associate at the Clinical Mass Spectrometry Facility in the Division of Pathology and Laboratory Medicine at Cincinnati Children’s Hospital Medical Center. He is currently focusing on the biomarker discovery with metabolomics and lipidomics approaches to study pathogenesis of pediatric diseases. He has also been developing mass spectrometry assays for pharmacokinetic studies and clinical assays. He obtained his PhD degree from University of Georgia and MS from Stanford University.

I am the Waters Senior Lecturer in Molecular Spectroscopy in the Department of Surgery and Cancer. I joined Imperial College in 2006 after working as a postdoctoral researcher at the Scripps Research Institute in La Jolla, CA. At Imperial College, I was initially a postdoctoral researcher for the Consortium for Metabonomic Toxicology (COMET) group.

My research focuses primarily on the development and application of novel mass spectrometry (MS) based techniques for metabolic phenotyping and on the fusion of mass spectrometric methods with chemometric analysis, which is currently a significant bottleneck in the analysis pipeline. Broadly, my research at Imperial College has involved the development, optimisation and application of UPLC-MS methodologies for the analysis of biological samples, largely in the context of metabolic phenotyping: serum, urine, tissue, amniotic fluid, and microdialysates. These developmental advances have resulted in shorter analysis times – and therefore higher sample throughput – key for large scale metabolic phenotyping studies. Peak detection and analytical reproducibility have been enhanced, improving metabolome coverage and the potential for biomarker identification and quantification.

I am applying these methods to biomedical research areas including toxicology, cardiovascular disease, neonatal disease and development, maternal exposures and effects on early childhood, and neurological diseases.

As an undergraduate, I studied Biomedical Engineering and Mathematics. I also developed microfluidic devices to study signaling dynamics in single immune cells. I then went out to the Bay Area, where I applied a combination of live-cell imaging and mathematical modeling to understand the dynamics of innate immune signaling. They eventually gave me a PhD in Bioengineering. I then did a postdoc, where I learned the wonder of applying computational methods to publicly available data to address basic biological questions and clinical needs. My research group uses data and computation to learn about biological systems relevant to human health and disease.

Sydney C. Povilaitis received her B.A. in Chemistry from St. Olaf College in Northfield, Minnesota in 2018. Currently, she is a graduate student in Prof. Livia S. Eberlin’s lab at the University of Texas at Austin. Her research focuses on developing the MasSpec Pen for molecular differentiation of microbes and skin lesions.

Alyson is a 4th year PhD student working under the mentorship of Drs. Anand Mehta and Richard Drake. She has developed a new tool for analysis of glycoproteins from biofluids and is using this to discover new cancer biomarkers. She is passionate about interdisciplinary science communication and teaching.

Jianhui Zhu, PhD, is a Lead Research Scientist in the Laboratory of Cancer Proteomics within the Department of Surgery at the University of Michigan. Dr. Zhu received her PhD degree from the Nanjing University, China. She joined the Lubman Group at the University of Michigan as a postdoc in 2010. She was appointed senior research scientist at the University of Michigan in 2015 and lead research scientist in 2018. Her research focuses on the development of mass spectrometry-based methods to identify cancer-related proteomic/glycomic/glycoproteomic markers in patient’s serum and tissue biopsies for early cancer detection and monitoring. She received the NCI Research Specialist Award in 2018 for novel glyco-marker research aimed at early detection of hepatocellular carcinoma.

I graduated in analytical chemistry from the faculty of chemistry at Shahid Beheshti University (Tehran,Iran).For my Master's thesis I was working on the Optimization of solid phase microextraction and electromembrane extraction techniques to measure certain pollutants and drugs. During my studies,I was also awarded medals and honorary diplomas from international and national competitions and expositions because of my inventions. In June 2017, I started my Glysign PhD project, conducting research at Genos Ltd., Zagreb, Croatia, and the Leiden University Medical Centre in Leiden, the Netherlands. My research is geared towards the quantification of serum protein glycosylation for patient stratification in early-onset and other diabetes types.

I hold a bachelor degree in Pharmacy from the Hebrew University of Jerusalem, Israel. I did my PhD at the same university specializing in nanocscience and drug delivery with Prof. Shlomo Magdassi (Chemistry Department). During my postdoctoral training with Prof. Richard Zare at Stanford University, USA I worked on ambient mass spectrometry imaging of clinical specimens, mostly employing Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI-MSI).
I started a tenure track position as a Senior Lecturer (Assistant Professor) at the School of Pharmacy, the Faculty of Medicine, the Hebrew University of Jerusalem, Israel, in September 2019.

Dr. E. Ellen Jones is a Staff Fellow at the National Center for Toxicological Research, which is part of the Food and Drug Administration, in Jefferson, AR. At NCTR Dr. Jones leads the MALDI Imaging team located within the Biomarkers and Alternative Models Branch (BAMB) in the Division of Systems Biology with the overall goal of utilizing this approach to better understand drug toxicities. The implementation of cutting-edge technologies such as high resolution MALDI IMS within the Food and Drug Administration (FDA) is critical as it corresponds to efforts ongoing in pharmaceutical companies whom are using it both in preclinical and clinical studies to identify biomarkers of drug efficacy and toxicity; data which is beginning to be included within FDA drug filings. Thus, the MALDI IMS team at NCTR recently acquired a state-of-the-art high resolution FTICR mass spectrometer (scimaX MRMS 7T FTICR MS) capable of the mass accuracy and resolution required for small molecule and metabolomic imaging.

I studied biology at the University of Zurich, Switzerland, and made my PhD in Molecular Plant Physiology in the lab of Prof. Enrico Martinoia, focusing on ABC transporters and comparative molecular phylogenetics. Subsequently, I became as researcher at the University Hospital of Zurich, where I was involved in establishing an LC/MS-based assay for the peptide hormone hepcidin and in projects studying Fabry Disease mechanisms. Biological processes, bioanalysis, clinical applications and the use of informatics to improve workflows have been my constant research interests. With this background I am now working as a senior researcher at the Singapore Lipidomics Incubator (SLING), heading our new data team that is focusing on developing workflows and software pipelines for the analytical data processing, QA/AC and exploration of the diverse lipidomics datasets generated by our lab.

Irene van den Broek has a PhD in analytical chemistry from the Utrecht University, the Netherlands and over 10 year experience in quantitative mass spectrometry for clinical and proteomics applications.

Distinguished Professor I. Fournier (IF, PRISM, U1192, Lille) is senior member of the University Institute (IUF) with a chair in Clinical Mass Spectrometry. She is currently co-director of PRISM lab INSERM U1192. Prof. Fournier is a specialist of Mass Spectrometry applied to clinics and proteomics. She was pioneer a novel technology in Europe of molecular imaging namely MALDI Mass Spectrometry Imaging in 2002 (Fournier et al., Neuroend. Letters 2003) and in 2007 demonstrated that MALDI MS Imaging could be perform from archived Formalin fixed and Paraffin Embedded hospital tissue samples (Lemaire et al., J. Proteome Res 2007). In 2005, she developed the multiplex targeted imaging, Tag-mass technology (Lemaire J. Proteome Res. 2007; Gagnon et al., Prog Histochem Cytochem 2012). In 2013, she introduced the concept of the spatially-resolved tissue proteomic and applied this technology on different cancers (Longuespee et al., Cancer Metastasis Rev 2012; Quanico et al Chem Com, 2015, Simeone et al., Semin Cancer Biol., 2018). Since 2011, Pr. I. Fournier with Pr. X. Roucou have evidenced the Ghost proteome (Samandi et al., Elife 2017, Delcourt et al., EBioMedicine et al., 2017, Brunet et al., Nucleic. Acid. Res., 2019). In 2014, she performed the development of a novel technology based on mass spectrometry and allowing to realize in vivo real time tissue molecular imaging and for guiding surgery, with an instrument named SpiderMass (Saudemont et al., Cancer cells, 2018; Ogrinc et al., Nature Protocols, 2019).

David C. Muddiman is the Jacob and Betty Belin Distinguished Professor of Chemistry and Director, Molecular Education, Technology, and Research Innovation Center (METRIC) at North Carolina State University in Raleigh, NC. Prior to moving his research group to North Carolina State University in 2006, David was a Professor of Biochemistry and Molecular Biology and Founder and Director of the Proteomics Research Center at the Mayo Clinic College of Medicine in Rochester, MN. Prior to this appointment, David was an Associate Professor of Chemistry at Virginia Commonwealth University. It was there that he began his professional career as an assistant professor with an adjunct appointment in the Department of Biochemistry and Molecular Biophysics and as a member of the Massey Cancer Center in 1997. These academic appointments followed a postdoctoral fellowship at Pacific Northwest National Lab

In 2018, Prof. David Muddiman was named the Director of the Molecular Education, Technology, and Research Innovation Center. METRIC provides NC State researchers and University partners with world-class state-of-the-art measurement science facilities across four buildings throughout campus, encompassing three key molecular characterization technologies including mass spectrometry, magnetic resonance (NMR and EPR), and X-Ray Crystallography (small molecule and macromolecular).

The Muddiman Group focuses on the development of innovative mass spectrometry measurements to solve important biological problems. Research projects include developing an ambient ionization method called IR-MALDESI and its application to a diverse range of materials, including soft tissue, plants, textiles and bone. Moreover, the group is working on advanced separations to enable detailed characterization of complex biological samples.

Wojciech Michno has a highly international background. He is a United World College (Norway) scholar and a Macalester College (USA) alumnus. At the university he completed two degrees in parallel, one in Chemistry and one in Neuroscience, with a focus on molecular neurobiology. Wojciech did his master’s thesis in pharmacology, and recently defended his PhD in analytical neurochemistry at Sahlgrenska Academy, University of Gothenburg, Sweden. The focus of his work is Alzheimer’s disease.

I am an analytical chemist focused on infection metallomics and clinical mass spectrometry (MS). From 1991 I have had the main contract with the Institute of Microbiology in Prague, where I run an analytical lab with 25 employees now benefitting from mass spectrometry, nuclear magnetic resonance spectroscopy, and electron microscopy (https://ms.biomed.cas.cz/). As a professor of analytical chemistry, I am also active at Palacky University in Olomouc, CZ, providing me with access to elemental imaging mass spectrometry and infection models. I have a scientific profile with 3582 citations (access date May 21, 2020), 1517 citations since 2015. My current h-index is 30 (Google Scholar). In 2020 I contributed to 11 peer-reviewed papers, nine of them I corresponded.

Background: The detection and quantitation of siderophores in urine represents an innovative early indication of pathogenic microorganisms in a host [1]. In this presentation, we document why the general application of siderophores in invasive infectious diagnostics will soon represent the same clinical breakthrough as ribosomal protein typing ten years ago. In addition to handling co-infections or polymicrobial frenemies, with mass spectrometry, we can monitor the antimicrobial drug metabolism [2].

Methods: A database of 700 microbial siderophores was used for screening a patient’s status with invasive infections caused by Aspergillus fumigatus, Pseudomonas aeruginosa, and zygomycetes. Human urine samples were examined by liquid chromatography and Fourier-transform ion cyclotron resonance (FTICR) mass spectrometer [3]. The biomarkers were quantified against matrix-matched standards, and our in-house tool called CycloBranch (https://ms.biomed.cas.cz/cyclobranch) was used for compound dereplication [4].

Results: For the diagnosis of aspergillosis, we used an array of ferri-triacetylfusarinine C (TAFC)/ferri-ferricrocine (FC)/gliotoxin (GTX) in a cohort of 28 patients (14 positive and 14 negative controls). LOD for TAFC in human urine was 0.1 ng/mL. The maximum experienced concentration was 1.7 ug/mL. In the working dataset of critically ill, mostly non-neutropenic humans, the TAFC/FC/GTX sensitivity in urine was 93% compared to standard GM in serum (36%). The kinetic profiles upon antimycotic treatment showed a quick drop in siderophore production in vivo. In the same cohort, ferri-pyoverdines and pyochelin were detected as urinal biomarkers in the patients with Pseudomonas aeruginosa. The LOD for Fe-PVD in urine was 10 ng/mL. In serum samples, the LOD and LOQs were 1 and 5 ng/mL, respectively. In the seminar I will also show the co-infecting frenemies studied in animal models of bacterial [5] or fungal infections [6].

Conclusion: Urinal samples are analytically attractive due to less chemical background compared to serum and clinically interesting due to non-invasive applications. Optimized sample preparation could soon move siderophore analysis from FTICR equipment to standard MALDI-Biotyper-type labs.

References:

1. Luptáková, D.; Pluhá?ek, T.; Pet?ík, M.; Novák, J.; Palyzová, A.; Sokolová, L.; Škríba, A.; Šedivá, B.; Lemr, K. and Havlí?ek, V. Non-invasive and invasive diagnoses of aspergillosis in a rat model by mass spectrometry. Sci Rep 2017, 7, 16523.

2. Houst, J.; Spizek, J. and Havlicek, V. Antifungal Drugs. Metabolites 2020, 10, article No. 106.

3. Pluhacek, T.; Skriba, A.; Novak, J.; Luptakova, D. and Havlicek, V. Analysis of Microbial Siderophores by Mass Spectrometry. In: SK Bhattacharya (ed) Metabolomics: Methods and Protocols 2019: 131-153.

4. Novák, J.; Škríba, A. and Havlí?ek, V. CycloBranch 2: Molecular Formula Annotations Applied to imzML Data Sets in Bimodal Fusion and LC-MS Data Files. Anal Chem 2020, 92, 6844-6849.

5. Petrik, M.; Umlaufova, E.; Raclavsky, V.; Palyzova, A.; Havlicek, V.; Haas, H.; Novy, Z.; Dolezal, D.; Hajduch, M. and Decristoforo, C. Imaging of Pseudomonas aeruginosa infection with Ga-68 labelled pyoverdine for positron emission tomography. Sci Rep 2018, 8, 15698.

6. Skriba, A.; Pluhacek, T.; Palyzova, A.; Novy, Z.; Lemr, K.; Hajduch, M.; Petrik, M. and Havlicek, V. Early and Non-invasive Diagnosis of Aspergillosis Revealed by Infection Kinetics Monitored in a Rat Model. Front Microbiol 2018, 9, 2356.

Michael H. Gelb is Professor of Chemistry and Barbara L. Weinstein Endowed Chair in Chemistry, Adjunct Professor of Biochemistry at the University of Washington. Major developments in the Gelb lab include discovery of protein prenylation, development of ICAT proteomic reagents, identification of phospholipases involved in lipid mediator generation, development of anti-parasite drugs, and development of mass spectrometry for newborn screening. Awards include: Repligen Award in Chemistry of Biological Processes (Amer. Chem. Soc.), Univ.of Washington Faculty Lecture Award, Gustavus John Esselen Award (Harvard Univ.), AAAS Fellow, NIH Merit Award, Medicines for Malaria Project of the Year Award, Pfizer Award in Enzyme Chemistry, ICI Pharmaceuticals Award for Excellence in Chemistry. The Gelb lab has published more than 500 papers and 100 patents in biological chemistry. The Gelb laboratory has developed mass spectrometry for worldwide newborn screening of lysosomal storage diseases (the latest expansion of newborn screening panels).

Mass spectrometry has a strong presence in newborn screening laboratories because of the ability to quantify numerous metabolites in dried blood spots on newborn screening cards. Over the past decade mass spectrometry has been developed to measure enzymatic activities in dried blood spots. We will present an 18-plex mass spectrometry assay that provides enzymatic activities and biomarkers for lysosomal diseases and allows consolidation with existing mass spectrometry newborn screening panels. In the second part of the presentation we will show the feasibility of using mass spectrometry for proteomics-based newborn screening. This allows screening for a panel of treatable diseaes for which no other methods exists.
As more and more inborn errors become treatable, in part due to gene therapy, it will be important to develop a universal screening platform that allows high throughput, consolidated newborn screening. Despite great progress in DNA sequencing technology, this will not replace biochemical newborn screening in the foreseable future.

INTRODUCTION: Cystic Fibrosis is a disease caused by mutations in the cystic fibrosis ion transport regulator gene (CFTR). The most common mutation, deletion of Phe at position 508 (DF508), results in a loss of function phenotype that causes a large number of clinical symptoms including chronic respiratory infections. At the protein level, the DF508 mutation causes the protein to misfold which results in rapid degradation of the protein in the ER.

OBJECTIVES: The objective of this study is to understand the mechanisms involved in regulating protein misfolding to learn how to rescue the misfolded protein. A detailed understanding of the mechanism should lead to the identification of drug targets for treatment of the disease.

METHODS: Mass spectrometry-based proteomics was used to identify the proteins interacting with wild type CFTR and DF508 CFTR to identify those proteins interacting with the mutant protein, but not the wild type. Proteins interacting uniquely with the mutant were knocked down to identify those proteins whose “inhibition” could potentially rescue the misfolded protein. In addition, regulation of the trafficking process by post translational modifications was also determined using mass spectrometry.

RESULTS: A much better understanding of the mechanisms behind rescue of the mutant protein has been derived from these studies. A disease specific interactome was identified. Proteins interacting with DF508 whose knockdown rescue the mutant protein have been identified. A PTM code has been identified that must be present for the protein to exit the ER. In addition, structural details of the misfolded protein have been determined using a surface accessibility method.

CONCLUSION: By understanding the mechanism behind the loss of function phenotype of DF508 CFTR we now have better routes to rescue the protein and treat CF disease. This knowledge can be used to understand other mutations in the gene that also result non-trafficking of the protein.