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Presenters* include:

Silvia Cavagnero, PhD | Professor and Associate Director
University of Wisconsin-Madison (USA)
LC-Photo-CIDNP and Isotopologs as Powerful Tools to Increase the Sensitivity of Biomolecular NMR Spectroscopy

Tuo Wang, PhD | Carl Brubaker Professor
Michigan State University (USA)
How Isotope-Labeling Strategies Can Help Us Better Visualize Cellular Samples by Solid-State NMR and DNP

Joshua Ziarek, PhD | Associate Professor, Pharmacology
Northwestern University (USA)
Designing Better Cysteine-reactive ¹⁹F Probes to Reveal Protein Conformation and Dynamics

Facilitator:

Kelly Andrade
Product Manager - NMR
Cambridge Isotope Laboratories, Inc. (USA)

*Presenter biographies and presentation abstracts can be found below.

Presenters* include:

Franz Schilling, PhD | Professor 
Technical University Munich (Germany)
Molecular MRI of Metabolism, pH and Cell Death

Kumar Pichumani, PhD | Professor
Houston Methodist Research Institute (USA)
Probing Nutrient Utilization in Human Brain Tumors Using ¹³C Isotopomer Analysis

Eduard Chekmenev, PhD | Professor of Chemistry and Oncology
Wayne State University (USA)
High-Throughput Pyruvate-to-Lactate Flux Profiling in Leukemia and Breast Cancer Using All-Benchtop SABRE Hyperpolarization and 1.4 T ¹³C NMR Spectroscopy in Cellular and PDX Models 

Henk De Feyter, PhD |  Associate Professor
Yale University (USA)
Deuterium Metabolic Imaging (DMI) to Characterize Brain Tumors in vivo

Facilitator:

Roswell Shelhamer
Business Development Manager
Cambridge Isotope Laboratories, Inc. (USA)

*Presenter biographies and presentation abstracts can be found below.

Presenters* include:

Xiangqiu (Sam) Liang | Environmental Investigator V
City of Houston Wastewater Program (USA)
Optimized Internal Calibration Models for EPA Methods 1633A and 533

transcript

Allycia Weibel | Laboratory Scientist
Michigan Department of Health & Human Servies Bureau of Laboratories (USA)
Use of CIL ES-5660 Custom Internal Standard Mixture for Analysis of Persistent Organic Pollutants in Fish

transcript

Fuhar Dixit, PhD | Assistant Professor
University of Tennessee Knoxville (USA)
Improved TOP Assay for Detection of PFAS Precursors in the Environment

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Jonathan Thorn | Technical Director and PFAS Practice Leader
Eurofins (USA)
Characterization of Ultra-Short Chain PFAS in Aqueous and Solid Matrices

Recording and transcript not available

Facilitator:

Ben Priest
Business Development Manager- Environmental
Cambridge Isotope Laboratories, Inc. (USA)

*Presenter biographies and presentation abstracts can be found below.

Presenters* include:

Ralph DeBerardinis, MD, PhD | Professor and Director
Eugene McDermott Center for Human Growth and Development | UT Southwestern (USA)
Stable Isotope Tracing to Identify Metabolic Preferences and Liabilities in Cancer

Recording and transcript not available

Gary Patti, PhD | Professor
Chemistry, Genetics, and Medicine | Washington University in
St. Louis (USA)
Isotopes at the Nexus of Metabolism Research

transcript

Timon Geib, PhD | Research Associate
Segal Cancer Proteomics Centre'(Canada)
Cost-Effective and Comprehensive Tissue-Specific Absolute Quantification Using SysQuan

transcript

Facilitator:

Andrew Percy, PhD
Senior Technical Product Manager
Cambridge Isotope Laboratories, Inc. (USA)

*Presenter biographies and presentation abstracts can be found below.

 Biographies and Abstracts – Environmental Analysis

Xiangqiu (Sam) Liang | Environmental Investigator V
Houston Department of Wastewater(USA)

With 37 years of experience in commercial and public laboratories, including entrepreneurial leadership during the startup and expansion of analytical and oil/gas research labs. Highly skilled in developing and validating ultra‑trace analytical methods based on isotope‑dilution mass spectrometry and internal calibration using isotope‑labeled standards to achieve high‑accuracy quantitation. Expert in high‑resolution gas chromatography coupled with high‑resolution mass spectrometry (HRGC‑HRMS), with a strong track record setting up and optimizing regulatory and industry methods including USEPA, USFDA, ASTM, and UOP protocols. Extensive experience implementing GC, GC/MS, IC, HPLC‑MS, and IRMS methods for applications in hydraulic fracturing, petroleum characterization, and corrosion inhibitor studies. Currently overseeing organic analytical operations for the City of Houston wastewater program, specializing in detection and quantification of organic contaminants. Proficient in LC‑MS/MS method optimization, performance improvement, and validation of EPA 1633A and EPA 533 PFAS methods to ensure robust, reproducible, and ultra‑trace quantification in complex water and wastewater matrices.

Optimized Internal Calibration Models for EPA Methods 1633A and 533

Linear regression fitting in PFAS internal calibration is challenging due to the complexity of PFAS chemistry, matrix effects, and the need for high precision at trace levels. Collaborative work with Cambridge Isotope Laboratories, Inc (CIL) has improved the application of stable isotope labeled standards (SIL) and has incorporated additional SILs into EPA Methods1633A and 533. Both methods provide limited guidance for the appropriate application and evaluation of the internal standard calibration model. The internal standard calibration involves adding non-interfering reference standards to target compounds. The model compares how the detector responds to the target compound relative to how it responds to the reference (internal) standard. The improved fit of the calibration model can improve performance and expand the calibration range while maintaining low relative standard deviations and avoiding the use of a quadratic curve model.

During this talk you will learn about:

• What is internal calibration in LC‑MS/MS PFAS analysis?
• How do you select appropriate isotopically labeled internal standards?
• How do you achieve a proper linear regression fit and meet RSD% criteria required by EPA Methods 1633A and 533?

Allycia Weibel | Laboratory Scientist
Michigan Department of Health & Human Servies Bureau of Laboratories (USA)

Allycia Weibel is a laboratory scientist in the Environmental Organic Unit (EOU) of the Division of Chemistry and Toxicology at the Michigan Department of Health & Human Servies Bureau of Laboratories. She is the team lead for the State's PCB/Pesticide/PBDE environmental testing and is also on the teams testing for PFAS, CoPCBs, PCDDs, and PCDFs in tissue.

Use of CIL ES-5660 Custom Internal Standard Mixture for Analysis of Persistent Organic Pollutants in Fish

The State of Michigan's Fish Monitoring Program assesses the presence of persistent organic pollutant (POP) contamination in fish from the state's surface waters. The data generated is used to determine whether fish from waters of the state are safe for human and wildlife consumption, and as a surrogate measure of bioaccumulative contaminants in surface water. The scope of testing includes PCB, OCP, PBDE, PCDD, PCDF, and PFAS analytes. In Michigan, an 'Eat Safe Fish' report is generated for the public yearly. Testing for PCB, OPC, PBDE, PCDD, PCDF analytes depend on a number of CIL standards, including the ES-5660 PCB/Pesticide/BDE Mixture is used as the internal standard, which is used for the 131-analyte panel in the PCB/OCP/PBDE method.

During this talk you will learn about:

• The role of the Michigan Department of Health & Human Services in environmental monitoring for the state
• he scope and scale of environmental testing that depend on CIL standards
• How CIL contributes to the health and well-being of the people of Michigan

Fuhar Dixit, PhD | Assistant Professor
University of Tennessee Knoxville (USA)

Dr. Fuhar Dixit is an assistant professor at the University of Tennessee Knoxville (UTK) and conducts research in environmental chemistry, polymers, water treatment, and pollutant fate. As a core faculty member of the Precision Health and Environment Cluster, he oversees facilities bridging engineering and public health and mentors doctoral students through the Bredesen Centre, facilitating research links with Oak Ridge National Laboratory (ORNL). He currently leads high-impact collaborations with industry and federal agencies, to develop a standardized total oxidizable precursor (TOP) Assay for the measurement of PFAS precursors. He has been awarded prestigious fellowships, including the University of California (UC) President’s Lindau Nobel Laureate Meeting Fellow in 2025.

Improved TOP Assay for Detection of PFAS Precursors in the Environment

Comprehensive characterization of per- and polyfluoroalkyl substance (PFAS) contamination remains challenging because conventional targeted methods cannot account for unidentified PFAS precursors. The total oxidizable precursor (TOP) assay is commonly applied to estimate these unmeasured precursors; however, incomplete precursor oxidation caused by matrix-dependent effects has been reported. Such limitations can be assessed using stable-isotope-labeled oxidation surrogates, although existing surrogates are not compatible with EPA Method 1633A. To address this limitation, we developed an isotopically labeled surrogate system consisting of ¹³C₃-PFHpSA as an oxidation surrogate, ¹³C₃-PFHpA as a transformation surrogate, and ¹³C₃-PFNA as a stable extraction surrogate. Together, these compounds enable evaluation of recovery throughout the TOP assay workflow and are designed for compatibility with EPA Method 1633A without introducing analytical interference. Our findings demonstrate that surrogate-based quality controls can strengthen interpretation and improve the reliability of TOP assay results, particularly when analyzing complex environmental samples.

Jonathan Thorn | Technical Director and PFAS Practice Leader
Eurofins (USA)

Jonathan Thorn is Technical Director and PFAS Practice Leader at Eurofins Environment Testing. Jon has worked in the field of environmental analytical chemistry for more than 30 years. For the last 12 years, his primary focus has been the analysis of PFAS in environmental samples, focusing on development and implementation of analytical methods in difficult matrices, including ground water, wastewater, landfill leachate, sediment, soil, biosolids, environmental tissues, agricultural products, animal blood, and consumer products.

Characterization of Ultra-Short Chain PFAS in Aqueous and Solid Matrices

Ultrashort-chain PFAS (C1–C3), including trifluoroacetic acid (TFA), perfluoropropanoic acid (PFPrA), and trifluoromethanesulfonic acid (TFMS), are highly mobile, persistent, and poorly removed by conventional treatment. TFA is now reported across nearly every environmental matrix and was recently identified as the most abundant individual PFAS in a European general-population blood cohort. Regulatory attention is accelerating: ECHA's Risk Assessment Committee has adopted an opinion classifying TFA as Reprotoxic Category 1B, EPA has issued screening levels for PFPrA and TFSI, and draft EPA Method 563 targets seven ultrashort compounds for proposed UCMR 6 monitoring. Most existing PFAS regulations and methods, however, remain limited to C4 and longer chains. This presentation reviews ultrashort PFAS definitions, sources, and occurrence in the EU, Canada, and the United States, followed by an overview of available analytical methods: draft EPA 563, ASTM D8628-25, laboratory based methods, and the limitations of Adsorbable Organic Fluorine (AOF) for ultrashort compounds. Application data include wastewater influent, effluent, and biosolids.

 Biographies and Abstracts – NMR

Silvia Cavagnero, PhD | Professor and Associate Director
University of Wisconsin-Madison (USA)

Silvia Cavagnero is a Professor of Chemistry at the University of Wisconsin-Madison, where she is also Associate Director of the UW-Madison Biophysics Program and Co-Director of the NIH -32 Molecular Biophysics Training Grant. She received her PhD at CALTECH with Sunney I. Chan and did her postdoc at the Scripps Research Institute with Peter E. Wright. Her work pioneers novel optically enhanced approaches to generate NMR hyperpolarization in liquids for biomolecular NMR applications. She also explores the early stages of protein folding, dynamics and aggregation in the cell, including the role of the ribosome and molecular chaperones via a combination of NMR, time-resolved fluorescence and single-particle cryo-EM.

LC-Photo-CIDNP and Isotopologs as Powerful Tools to Increase the Sensitivity of Biomolecular NMR Spectroscopy

Nuclear magnetic resonance spectroscopy is hampered by extremely low sensitivity. This presentation will explain how low-concentration photochemically induced dynamic nuclear polarization (LC-photo-CIDNP) is able to overcome this challenge by enabling ultra-rapid NMR data collection in solution across the low-micromolar-to-nanomolar concentration range. Recent conceptual advances and practical implementations of LC-photo-CIDNP to the nuclear-spin hyperpolarization of amino acids and proteins will be discussed, highlighting the power of amino acids bearing selective isotopic substitutions and quasi-isolated spin pairs (QISP) to dramatically increase the hyperpolarization levels of biomolecules in solution.

During this talk you will learn about:

• We need better tools to increase the sensitivity of NMR spectroscopy
• LC-Photo-CIDNP is a powerful tool to readily and cost-effectively generate NMR hyperpolarization
• Amino acid isotopologs, including quasi-isolated spin pairs, play a key role in rendering NMR spectroscopy more sensitive

Tuo Wang, PhD | Carl Brubaker Professor
Michigan State University (USA)

Tuo Wang received his B.S. degree from Nankai University (Tianjin, China) and started his graduate research at Iowa State University in 2010. In 2014, he moved to MIT (with Prof. Mei Hong) and received his Ph.D. degree in January 2016 in the field of physical chemistry from MIT. He continued at MIT for his postdoctoral training. He joined the faculty at LSU as an assistant professor in July 2017 and becomes an Associate Professor in Aug 2021. In August 2022, he joined Michigan State University as the Carl Brubaker Associate Professor in Chemistry. On July 1, 2025, he is promoted to Carl Brubaker Professor. His research focuses on the application of solid-state NMR and DNP methods to cellular samples and complex carbohydrates.

How Isotope-Labeling Strategies Can Help Us Better Visualize Cellular Samples by Solid-State NMR and DNP

Extracellular matrices play crucial roles in cellular structure and function, yet their structural characterization remains technically challenging. Recent advances in solid-state NMR spectroscopy, including 13C/15N-detected and 1H-detected methods, often combined with dynamic nuclear polarization (DNP), have significantly improved our understanding of extracellular matrices in plant and fungal cells. These insights have important implications for both bioenergy applications and biomedical challenges, including antifungal resistance. Here, we demonstrate how diverse isotope-labeling strategies can expand the capabilities of solid-state NMR for studying complex cellular samples. Specifically, these approaches can be used to 1) distinguish newly synthesized macromolecules from pre-existing cellular components, enabling the investigation of structural remodeling over time; 2) selectively track specific regions or components of biomacromolecules synthesized from different precursors, providing insights into their structural and functional roles; and 3) improve the spectral resolution of 1H-detected solid-state NMR measurements. By strategically combining different precursors, these labeling schemes provide complementary temporal, structural, and functional information while reducing spectral complexity. These approaches could pave the way toward high-resolution, time-resolved characterization of structural remodeling events occurring within living cells.

During this talk you will learn about:

• Distinguish newly synthesized macromolecules from pre-existing cellular components
• Selectively track specific regions or components of biomacromolecules synthesized from different precursors
• Improve the spectral resolution of 1H-detected solid-state NMR measurements

Joshua Ziarek, PhD | Associate Professor, Pharmacology
Northwestern University (USA)

Joshua Ziarek is an Associate Professor of Pharmacology at Northwestern University Feinberg School of Medicine. His research has revealed how ligands and signaling partners reshape G protein-coupled receptor conformational ensembles, helping explain how these receptors produce distinct cellular responses. Alongside these biological studies, his laboratory develops NMR methods and labeling strategies that improve and expand measurements of protein conformational dynamics. His research brings together molecular mechanisms and experimental innovation to understand how protein motion governs function. He earned his PhD at the Medical College of Wisconsin with Prof. Brian Volkman and completed his postdoctoral training at Harvard Medical School with Prof. Gerhard Wagner.

Designing Better Cysteine-reactive ¹⁹F Probes to Reveal Protein Conformation and Dynamics

Cysteine-reactive ¹⁹F NMR probes are valuable reporters of biomolecular structure and dynamics, but rapid transverse relaxation and spectral overlap limit their application. Guided by electronic structure and spin relaxation calculations, we developed aromatic ¹⁹F-¹³C probes whose chemical shielding tensors favor relaxation suppression through the TROSY effect. Our first-generation probe, 2,4-dichloro-5-fluoro-5-13C-pyrimidine (2Cl-4Cl), selectively conjugates to cysteine through nucleophilic aromatic substitution (SNAr) to yield a rigid thioether linkage that minimizes internal motion. Solid-state magic-angle spinning NMR supports the predicted shielding tensor geometry, while measurements on 42 kDa maltose-binding protein (MBP) demonstrate approximately 21% and 83% reductions in 19F and 13C transverse relaxation rates, respectively, when compared to decoupled baseline rates. Applying these design principles yielded a next-generation probe. When attached to MBP, the next-generation produces 19F linewidths of 4.6-4.8 Hz, compared with 18-29 Hz for 2Cl-4Cl, and retains resolved two-dimensional TROSY correlations under conditions that mimic megadalton-scale rotational tumbling. Multiplexed labeling enables simultaneous monitoring of conformational responses at multiple protein sites. Together, these results establish chemical shielding tensor engineering and strategic isotope placement as complementary tools for developing high-resolution NMR reporters, expanding opportunities to investigate large biomolecular systems without uniform protein isotope enrichment.

During this talk you will learn about:

• We can design an aromatic fluorine probe’s relaxation properties through its chemistry.
• The bonded ¹⁹F-¹³C spin pair enables TROSY effect and a second spectral dimension.
• Superior relaxation properties allow us to label multiple sites simultaneously and observe them at high molecular weights.

 Biographies and Abstracts – DMI/Hyperpolarization

Franz Schilling, PhD | Professor
Technical University Munich (Germany)

Prof. Schilling conducts research in the field of molecular imaging. His research focusses on the development of novel methods in the area of magnetic resonance imaging (MRI). Together with his group he characterizes and validates imaging biomarkers. Interdisciplinarity is an essential characteristic of this area of research which combines the development of physical methods, the chemical characterization and synthesis of molecular sensors, as well as the investigation of biological and medical research questions. Prof. Schilling studied physics at the University of Würzburg and the University of California (Berkeley). He obtained a PhD from TUM focusing on nuclear magnetic resonance. During postdoctoral research at the University of Cambridge he deepened his interest for molecular imaging. Since 2017 he leads an independent research group at the Klinikum rechts der Isar at TUM. In 2019 he was appointed Assistant Professor and in 2025 Associate Professor of Biomedical Magnetic Resonance at TUM.

Molecular MRI of Metabolism, pH and Cell Death

For patients, specific non-invasive imaging strategies for early-stage disease characterization and evaluation of response to therapy are not available at a satisfactory level so far, creating a pressing need for innovative technologies. The goal of my research is to develop novel non-invasive magnetic resonance imaging biomarkers for the characterization of tissue physiology, metabolism and response to therapy. Here, I will present recent developments from our group on pH-sensitive hyperpolarized molecules, multimodal metabolic imaging and advanced diffusion MRI techniques for detection of early cell death. Their translation from preclinical discoveries to clinical implementation will be covered and their potential clinical value will be discussed.

During this talk you will learn about:

• How hyperpolarized MRI can be used to develop novel imaging biomarkers
• How diffusion MRI can be used to detect transmembrane water exchange
• How novel MRI biomarkers can be translated to the clinic

Kumar Pichumani, PhD | Professor
Houston Methodist Research Institute (USA)

Dr. Kumar Pichumani is an Associate Professor of Neurosurgery and the Dagmar Dunn Pickens Gipe Distinguished Professor in Brain Tumor Research at Houston Methodist Research Institute, with an academic appointment at Weill Cornell Medicine. His NIH-funded research focuses on understanding nutrient utilization and metabolic pathways in human brain tumors using stable-isotope ¹³C tracing and NMR spectroscopy. His work integrates intraoperative metabolic tracing in patients with metabolomic analyses and patient-derived tumor models to investigate metabolic vulnerabilities and therapeutic resistance. His research spans gliomas, meningiomas, and pediatric brain tumors, with an emphasis on translational applications of cancer metabolism.

Probing Nutrient Utilization in Human Brain Tumors Using ¹³C Isotopomer Analysis

We will demonstrate the utility of stable-isotope ¹³C-labeled nutrient tracers for investigating and quantifying metabolic pathway activity in human brain tumors. Using intraoperative administration of ¹³C-labeled nutrients, including glucose, acetate, glutamine, and β-hydroxybutyrate, we employ high-resolution ¹³C NMR spectroscopy and isotopomer analysis to track carbon utilization and metabolic flux through central metabolic pathways. We will present findings from multiple types of central nervous system tumors, including gliomas, meningiomas, and pediatric brain tumors, highlighting differences in nutrient utilization and metabolic reprogramming. These studies illustrate how patient-centered ¹³C metabolic tracing can provide functional insights into human tumor metabolism and identify potential metabolic vulnerabilities.

During this talk you will learn about:

• Understand the power of ¹³C metabolic tracing to investigate nutrient utilization and metabolic pathways directly in human brain tumors.
• Learn how ¹³C NMR spectroscopy and isotopomer analysis can track nutrient-derived carbon through central metabolic pathways and quantify relative metabolic contributions.
• Explore the biological and translational significance of nutrient utilization differences across CNS tumor types and how these findings may reveal metabolic vulnerabilities and therapeutic opportunities.

Eduard Chekmenev, PhD | Professor of Chemistry and Oncology
Wayne State University (USA)

Dr. Chekmenev serves as a professor of Chemistry and Oncology at Wayne State University. He also co-leads Molecular Therapeutics (MT) research program at Karmanos Cancer Institute (KCI), a comprehensive NCI-designated cancer center located in mid-town Detroit. The key focus of his research efforts is on the development of high-throughput technologies using NMR hyperpolarization to enable molecular imaging of cancer, neurodegeneration and lung diseases via hyperpolarized MRI and spectroscopy. Dr. Chekmenev research program has been supported by 24 grants and contracts, including CDMRP, NIH, NSF and DOE, with 6 active lines of research funding. He has co-authored 20 patents and over 200 scientific peer-reviewed publications, which have been cited over 15,000 times with h-index = 66. Dr. Chekmenev co-founded two startup companies.

High-Throughput Pyruvate-to-Lactate Flux Profiling in Leukemia and Breast Cancer Using All-Benchtop SABRE Hyperpolarization and 1.4 T ¹³C NMR Spectroscopy in Cellular and PDX Models

Cancer cells utilize altered metabolic pathways to support rapid proliferation and survival. Elevated glycolysis is a hallmark of many cancers’ aggressiveness and resistance to therapy. Realtime sensing of glycolysis flux is feasible using NMR spectroscopy relying on hyperpolarized [1-¹³C]pyruvate, which enhances the detection sensitivity by five orders of magnitude and makes it feasible to perform sensing of hyperpolarized [1-¹³C]pyruvate to hyperpolarized [1-¹³C]lactate conversion via benchtop NMR spectroscopy in cancer cells in cellular media. We demonstrate the feasibility of performing Michaelis-Menten kinetics measurement in live cancer cells. The technique has been successfully applied to probe chemotherapy resistance in Acute Myeloid Leukemia cell lines and patient-derived xenograft model, paving the way to near-future clinical studies. We have also successfully applied this method to differentiate metastatic from non-metastatic breast cancer cell lines and also to primary brain cells for future applications to other cancers and neurodegeneration. To produce hyperpolarized pyruvate, a rapid Signal Amplification By Reversible Exchange technique is utilized, relying on simultaneous chemical exchange of parahydrogen and pyruvate molecules, allowing to produce 8-16 hyperpolarized samples per day using manual workflow, which we envision expanding to up to 96 samples per day via process automation and integration.

Henk De Feyter, PhD |  Associate Professor
Yale University (USA)

Henk De Feyter is an Associate Professor in the Department of Radiology and Biomedical Imaging at the Yale School of Medicine. Originally from Belgium, where he got a degree as physical therapist, he moved to the Netherlands and got his PhD in biomedical NMR at the Eindhoven University of Technology, and then joined the MR Research Center at Yale University as a postdoc with Prof. Douglas Rothman. His research is focused on applying advanced magnetic resonance spectroscopy techniques combined with the use of stable isotopes to study metabolism in vivo, with a particular interest in brain tumors.

Deuterium Metabolic Imaging (DMI) to Characterize Brain Tumors in vivo

Deuterium metabolic imaging (DMI) is a relatively new magnetic resonance (MR)-based approach to detect active metabolism in vivo during or following administration of a deuterated substrate of interest. In this presentation we will discuss the basic MR physics of 2H MR detection, the data acquisition and processing. We will dive into the use of [6,6’-2H2]-glucose, the most common DMI substrate used in humans. This includes variations in DMI acquisition methods, and interpretation. At Yale, we have active ongoing preclinical and clinical research studies using DMI with 2H-glucose to characterize metabolism in the context of brain cancer. Several examples will be presented on its potential in the clinic, as well as ongoing work in animal models, including the use of non-glucose DMI agents.

During this talk you will learn about:

• Basic principles underlying of deuterium metabolic imaging
• Different deuterated substrates being used in preclinical and clinical research settings
• Get an idea about the potential impact of DMI of glucose metabolism in patients with a brain tumor

 Biographies and Abstracts – Mass Spectrometry

Ralph DeBerardinis, MD, PhD | Professor and Director
Eugene McDermott Center for Human Growth and Development | UT Southwestern (USA)

Ralph DeBerardinis, MD, PhD is a pediatrician, biochemical geneticist and physician-scientist. He is an investigator in the Howard Hughes Medical Institute, director of the Eugene McDermott Center for Human Growth and Development at the University of Texas Southwestern Medical Center, and director of the Genetic and Metabolic Disease Program in UT Southwestern’s Children’s Research Institute. Dr. DeBerardinis received a BS in Biology from St. Joseph’s University, MD and PhD degrees from the University of Pennsylvania and clinical training at Children’s Hospital of Philadelphia. The DeBerardinis lab studies the role of altered metabolic pathways in human diseases, particularly cancer and inborn errors of metabolism. The lab uses metabolomics and isotope tracing to characterize disease-associated metabolic states in patients, and model systems to explore how metabolic perturbations contribute to tissue dysfunction. Dr. DeBerardinis has been elected to the National Academy of Sciences, National Academy of Medicine and Association of American Physicians.

Stable Isotope Tracing to Identify Metabolic Preferences and Liabilities in Cancer

We are interested in how cellular metabolism enables cancer progression, including metastasis and therapy resistance. Using human intra-operative isotope tracing in localized, primary tumors in patients, we identified mitochondrial oxidation of pyruvate as a pathway that predicts and promotes metastatic dissemination and early death. We further found that the ability to oxidize pyruvate and other nutrients in the mitochondria is closely linked to how cells balance de novo purine biosynthesis (DNPB) and purine salvage, the two pathways cells use to synthesize purine nucleotides. Cells capable of switching from DNPB to salvage can sustain their proliferation during mitochondrial dysfunction. DNPB and salvage are alternatively regulated, such that the more energetically demanding DNPB is suppressed when purine nucleotides can be generated through salvage. But the factors determining how cells switch between DNPB and salvage are incompletely understood. A screen for genes required to suppress DNPB when purines are abundant uncovered NUDT5, a Nudix family hydrolase. Surprisingly, this effect does not involve NUDT5’s known catalytic function of cleaving ADP-ribose but rather requires a physical association between NUDT5 and phosphoribosyl pyrophosphate amidotransferase (PPAT), the enzyme that catalyzes the committed step of DNPB. We identified two mechanisms by which NUDT5 regulates PPAT activity. First, when purine nucleotides are abundant, NUDT5 stimulates PPAT assembly from active dimers into a less active oligomeric state. Second, NUDT5 triggers disassembly of purinosomes, cytosolic supercomplexes containing PPAT and other DNPB enzymes that facilitate channeling of labile metabolic intermediates along the DNPB pathway. When purine nucleotide levels are high and NUDT5 can bind PPAT, purinosomes efficiently disassemble and DNPB is inactivated. Cells lacking NUDT5 or expressing a mutant that cannot associate with PPAT maintain inappropriate levels of purinosome assembly and DNPB even when purine nucleotides are abundant. Importantly, this allows cancer cells to resist thiopurine chemotherapies, which act in part by suppressing DNPB, both in culture and in vivo. Altogether, this work identifies NUDT5 as a natural regulator of the balance between two pathways of purine nucleotide synthesis, and a required factor for thiopurine sensitivity.

During this talk you will learn about:

• Understand the principles and rationale of intra-operative isotope infusions in patients with cancer.
• Be familiar with evidence that mitochondrial metabolism in cancer cells promotes metastasis.
• Understand the role of NUDT5 in regulating purine nucleotide biosynthesis.

Gary Patti, PhD | Professor
Chemistry, Genetics, and Medicine | Washington University in St. Louis (USA)

Gary Patti is the Michael and Tana Powell Professor at Washington University in St. Louis, where he holds appointments in the departments of chemistry, genetics, and medicine. Dr. Patti is the Senior Director of the Center for Mass Spectrometry & Metabolic Tracing, Dean's Fellow of Advancement and Entrepreneurship, Director of Faculty Affairs in Chemistry, and the Chief Scientific Officer and Co-Founder of Panome Bio. Professor Patti’s research focuses on developing and applying mass spectrometry-based technologies to enhance our understanding of human diseases such as cancer. 

Isotopes at the Nexus of Metabolism Research

Profiling large, well-characterized cohorts has the potential to reveal unexpected features of human biology and generate new hypotheses about disease mechanisms. While such population studies are becoming increasingly common in genomics, achieving comparable scales in metabolomics is a challenge and has limited our understanding of human metabolism. Here, a project will be described that began with a metabolomics analysis of eight thousand people and ultimately led to a deeper appreciation of physiological glucose metabolism. Isotopes will be spotlighted as central to each stage of this work, from enabling batch corrections across mass spectrometry runs to tracing metabolite transfer between tissues in animal models. 

During this talk you will learn about:

• Isotopes can correct for experimental drift across thousands of mass spectrometry experiments.
• Metabolites exchanged between tissues can be tracked in animals with tracers.
• The composition of the gut microbiome influences the metabolism of dietary glucose, liver health, and the tumor macroenvironment. 

Timon Geib, PhD | Research Associate
Segal Cancer Proteomics Centre' (Canada)

Dr. Geib is a Research Associate and Project Manager with extensive experience in bioanalytical chemistry and mass spectrometry. He has experience in leading scientific projects involving complex sample matrices, and targeted and untargeted LC-MS. With a PhD in Chemistry from Université du Québec à Montréal (UQAM) and over a dozen publications, Timon specializes in proteomics, and has presented his work at numerous international conferences. He is trilingual (German, English, French) and holds several academic awards, including the MMSDG Michel Bertrand Award and the FRQNT Doctoral Scholarship.

Cost-Effective and Comprehensive Tissue-Specific Absolute Quantification Using SysQuan

Despite major technological advances, quantitative proteomics remains constrained by matrix and batch effects, complex fractionation workflows, and long chromatographic separations, limiting the detection of subtle yet biologically meaningful changes. Cross-laboratory reproducibility remains poor, while the high cost and limited availability of stable isotope-labeled (SIL) standards have restricted the widespread adoption of absolute quantification. SysQuan addresses these challenges by leveraging SIL mice as a universal internal standard for accurate, scalable proteome quantification. Enabling absolute quantification of ~60% of the human proteome at a cost of less than 0.5 cents per labeled peptide, SysQuan substantially reduces economic and logistical barriers. By simplifying workflows and improving robustness, it redefines the scope of reproducible quantitative proteomics. METHODS: C57BL/6 mice were fed a ¹³C-lysine–enriched diet to generate SIL reference material. Human and SIL mouse plasma and tissues were lysed in SDS buffer and mixed 1:1 based on protein concentration. Disulfide bonds were reduced with tris(2-carboxyethyl)phosphine (TCEP), cysteines alkylated with iodoacetamide, and proteins digested overnight with trypsin using S-Trap columns. Targeted analyses were performed by dynamic multiple reaction monitoring (MRM) on an Agilent 6495D triple quadrupole coupled to an Evosep One LC system. Untargeted analyses were conducted using a Bruker timsTOF HT and an Orbitrap Exploris 480, both interfaced with an Evosep One. RESULTS: Analysis of mixed human/SIL mouse plasma and tissue digests by 2D-LC-MS/MS enabled quantification of over 1,225 human plasma proteins based on co-detected SIL peptide counterparts. In kidney, liver, heart and lung tissues, 8,915, 7,122, 7,057 and 8,798 proteins were identified, respectively. Using synthetic light peptides, we developed up to 3,000 MRM assays. Leveraging these standards, reverse quantification of thousands of SIL mouse proteins is underway, with rigorous feature-level validation. Fully validated quantities in lyophilized SIL mouse plasma can then support absolute quantification of the human plasma proteome in single-acquisition workflows, eliminating the need for extensive calibration curves while increasing throughput and robustness. CONCLUSION: SysQuan enables affordable, scalable, and reproducible absolute proteome quantification with unprecedented cross-laboratory comparability, advancing data reuse and disease-focused proteomics.

During this talk you will learn about:

• A low-cost path to absolute quantification
• Broad proteome coverage data across tissues and plasma
• Method tested across multiple MS platforms