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Ralph DeBerardinis, 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
Gary Patti, PhD | Professor
Chemistry, Genetics, and Medicine | Washington University in
St. Louis (USA)
Isotopes at the Nexus of Metabolism Research
Timon Geib, PhD | Research Associate
Lady Davis Institute for Medical Research (Canada)
Cost-Effective and Comprehensive Tissue-Specific Absolute Quantification Using SysQuan
Facilitator:
Andrew Percy, PhD
Senior Technical Product Manager
Cambridge Isotope Laboratories, Inc. (USA)
*Presenter biographies and presentation abstracts can be found below.
Coming Soon
Webinar details for Isotope Days 2026, for NMR, Environmental Analysis and MRI/MRS and Hyperpolarization will be available in the coming weeks.
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Biographies and Abstracts – Mass Spectrometry
Ralph DeBerardinis, PhD | Professor and Director
Eugene McDermott Center for Human Growth and Development | UT Southwestern (USA)
Ralph DeBerardinis, M.D., Ph.D. 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 B.S. in Biology from St. Joseph’s University, M.D. and Ph.D. 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.
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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.
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Timon Geib, PhD | Research Associate
Lady Davis Institute for Medical Research 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 Ph.D. 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