About

Susan Sumner, PhD, is a Professor of Nutrition at UNC Chapel Hill’s Nutrition Research Institute (NRI) and the Director of the Metabolomics and Exposome Laboratory (MEL) at UNC Chapel Hill. Her research focuses on making personalized medicine and precision nutrition a reality by utilizing state-of-the-art metabolomics and exposome technologies to determine how molecules present in tissues and biological fluids are associated with health and wellness. Her team employs analytical methods to detect signals for thousands of molecules in biological specimens such as urine, serum, plasma, feces, sweat, tissues, and cells, using untargeted metabolomics to identify metabolites derived from endogenous processes, dietary intake, medications, drugs of abuse, and environmental chemicals. Her work has linked perturbations in endogenous metabolism and exposure to various chemicals with health outcomes including obesity, cognitive decline, reproductive effects, and cancer. Dr. Sumner’s research spans domains such as Maternal and Child Health, Diabetes and Kidney Disease, Toxicology, Cancer, Microbiome, and Addiction. She has led multiple projects funded by NIH institutes, including a 2019 grant from the NHLBI to discover biomarkers related to cardiovascular disease, and directs core facilities for metabolomics and exposome analysis at UNC. Her recent work includes developing tools for untargeted analysis to study environmental exposures throughout the lifespan and their impact on human health, as well as contributing to the NIH Nutrition for Precision Health Consortium to develop algorithms predicting individual responses to dietary intake.

Research topics

• Biology
• Bioinformatics
• Biochemistry
• Genetics
• Medicine
• Computer Science
• Artificial Intelligence
• Chemistry
• Internal medicine
• Cell biology
• Computational biology
• Data Mining
• Microbiology
• Endocrinology
• Pathology
• Gastroenterology
• Engineering
• Risk analysis (engineering)
• Evolutionary biology
• Immunology
• Chromatography
• Database
• Cancer research
• Management science

Selected publications

• Biodistribution, cardiac and neurobehavioral assessments, and neurotransmitter quantification in juvenile rats following oral administration of aluminum oxide nanoparticles

  UNC Libraries · 2026-04-14

  articleOpen access

  Little is known about the uptake, biodistribution, and biological responses of nanoparticles (NPs) and their toxicity in developing animals. Here, male and female juvenile Sprague-Dawley rats received four consecutive daily doses of 10 mg/kg Al₂ O₃ NP (diameter: 24 nm [transmission electron microscope], hydrodynamic diameter: 148 nm) or vehicle control (water) by gavage between postnatal days (PNDs) 17-20. Basic neurobehavioral and cardiac assessments were performed on PND 20. Animals were sacrificed on PND 21, and selected tissues were collected, weighed, and processed for histopathology or neurotransmitter analysis. The biodistribution of Al₂ O₃ NP in tissue sections of the intestine, liver, spleen, kidney, and lymph nodes were evaluated using enhanced dark-field microscopy (EDM) and hyperspectral imaging (HSI). Liver-to-body weight ratio was significantly increased for male pups administered Al₂ O₃ NP compared with control. HSI suggested that Al₂ O₃ NP was more abundant in the duodenum and ileum tissue of the female pups compared with the male pups, whereas the abundance of NP was similar for males and females in the other tissues. The abundance of NP was higher in the liver compared with spleen, lymph nodes, and kidney. Homovanillic acid and norepinephrine concentrations in brain were significantly decreased following Al₂ O₃ NP administration in female and male pups, whereas 5-hydroxyindoleacetic acid was significantly increased in male pups. EDM/HSI indicates intestinal uptake of Al₂ O₃ NP following oral administration. Al₂ O₃ NP altered neurotransmitter/metabolite concentrations in juvenile rats' brain tissues. Together, these data suggest that orally administered Al₂ O₃ NP interferes with the brain biochemistry in both female and male pups.

  PublisherDOI

• Advancing translational exposomics: bridging genome, exposome and personalized medicine

  Human Genomics · 2025-04-30 · 32 citations

  reviewOpen access

  Understanding the interplay between genetic predisposition and environmental and lifestyle exposures is essential for advancing precision medicine and public health. The exposome, defined as the sum of all environmental exposures an individual encounters throughout their lifetime, complements genomic data by elucidating how external and internal exposure factors influence health outcomes. This treatise highlights the emerging discipline of translational exposomics that integrates exposomics and genomics, offering a comprehensive approach to decipher the complex relationships between environmental and lifestyle exposures, genetic variability, and disease phenotypes. We highlight cutting-edge methodologies, including multi-omics technologies, exposome-wide association studies (EWAS), physiology-based biokinetic modeling, and advanced bioinformatics approaches. These tools enable precise characterization of both the external and the internal exposome, facilitating the identification of biomarkers, exposure-response relationships, and disease prediction and mechanisms. We also consider the importance of addressing socio-economic, demographic, and gender disparities in environmental health research. We emphasize how exposome data can contextualize genomic variation and enhance causal inference, especially in studies of vulnerable populations and complex diseases. By showcasing concrete examples and proposing integrative platforms for translational exposomics, this work underscores the critical need to bridge genomics and exposomics to enable precision prevention, risk stratification, and public health decision-making. This integrative approach offers a new paradigm for understanding health and disease beyond genetics alone.

  PublisherOA PDFDOI

• An untargeted metabolomic analysis of acute AFB1 treatment in liver, breast, and lung cells

  PLoS ONE · 2025-01-30 · 3 citations

  articleOpen accessCorresponding

  Aflatoxin B1 (AFB1) is a class 1 carcinogen and mycotoxin known to contribute to the development of hepatocellular carcinoma (HCC), growth impairment, altered immune system modulation, and malnutrition. AFB1 is synthesized by Aspergillus flavus and is known to widely contaminate foodstuffs, particularly maize, wheat, and groundnuts. The mechanism in which AFB1 causes genetic mutations has been well studied, however its metabolomic effects remained largely unknown. A better understanding of how AFB1 disrupts metabolism would provide insight into how this mycotoxin leads to carcinogenesis, growth impairment, and/or immunomodulation, and may reveal potential targets for pharmacological or nutritional interventions to protect against these effects. The current study evaluated the metabolomic effects of various doses (2.5 μM, 5 μM, 10uM) of AFB1 treatment to HepG2 (liver), MDA-MB-231 (breast), and A549 (lung) cells. Treated and control cells' metabolomic profiles were evaluated via ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Univariate and multivariate analyses revealed significant alterations in metabolite concentrations from each dose of AFB1 treatment in each cell type. Pathway analysis was then used to understand broader biochemical functions affected by AFB1 treatment in each cell type. HepG2 cell pathway analyses revealed significant pathway perturbations in lipid metabolism, carnitine synthesis, catecholamine biosynthesis, purine metabolism, and spermidine and spermine biosynthesis. Analysis of A549 cells found a greater emphasis of perturbations on various amino acids along with lipid synthesis-related pathways, and catecholamine biosynthesis. Finally, analysis of treated MDA-MB-231 cells found spermidine and spermine biosynthesis, carnitine synthesis, plasma membrane-related pathways (phosphatidylcholine synthesis and alpha linolenic acid and linoleic acid metabolism), and various amino acid metabolism pathways to be most affected. These highlighted pathways should be targeted in future investigations to evaluate their potential in mitigating or preventing the development of negative health effects associated with AFB1 exposure.

  PublisherDOI

• Selective Influence of Hemp Fiber Ingestion on Post-Exercise Gut Permeability: A Metabolomics-Based Analysis

  Nutrients · 2025-04-19

  articleOpen accessSenior author

  Objectives: This study investigated the effects of 2-week ingestion of hemp fiber (high and low doses) versus placebo bars on gut permeability and plasma metabolite shifts during recovery from 2.25 h intensive cycling. Hemp hull powder is a rich source of two bioactive compounds, N-trans-caffeoyl tyramine (NCT) and N-trans-feruloyl tyramine (NFT), with potential gut health benefits. Methods: The study participants included 23 male and female cyclists. A three-arm randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and 2-week washout periods. Supplement bars provided 20, 5, or 0 g/d of hemp hull powder. Participants engaged in an intensive 2.25 h cycling bout at the end of each of the three supplementation periods. Five blood samples were collected before and after supplementation (overnight fasted state), and at 0 h-, 1.5 h-, and 3 h-post-exercise. Five-hour urine samples were collected pre-supplementation and post-2.25 h cycling after ingesting a sugar solution containing 5 g of lactulose, 100 mg of 13C mannitol, and 1.9 g of mannitol in 450 mL of water. An increase in the post-exercise lactulose/13C mannitol ratio (L:13CM) was used as the primary indicator of altered gut permeability. Other outcome measures included muscle damage biomarkers (serum creatine kinase, myoglobin), serum cortisol, complete blood cell counts, and shifts in plasma metabolites using untargeted metabolomics. Results: No trial differences were found for L:13CM, cortisol, blood cell counts, and muscle damage biomarkers. Orthogonal partial least-squares discriminant analysis (OPLSDA) showed distinct trial differences when comparing high- and low-dose hemp fiber compared to placebo supplementation (R2Y = 0.987 and 0.995, respectively). Variable Importance in Projection (VIP) scores identified several relevant metabolites, including 3-hydroxy-4-methoxybenzoic acid (VIP = 1.9), serotonin (VIP = 1.5), 5-hydroxytryptophan (VIP = 1.4), and 4-methoxycinnamic acid (VIP = 1.4). Mummichog analysis showed significant effects of hemp fiber intake on multiple metabolic pathways, including alpha-linolenic acid, porphyrin, sphingolipid, arginine and proline, tryptophan, and primary bile acid metabolism. Conclusions: Hemp fiber intake during a 2-week supplementation period did not have a significant effect on post-exercise gut permeability in cyclists (2.25 h cycling bout) using urine sugar data. On the contrary, untargeted metabolomics showed that the combination of consuming nutrient-rich hemp fiber bars and exercising for 135 min increased levels of beneficial metabolites, including those derived from the gut in healthy cyclists.

  PublisherOA PDFDOI

• Exploratory Metabolomics Underscores the Folate Enzyme ALDH1L1 as a Regulator of Glycine and Methylation Reactions

  UNC Libraries · 2025-07-26

  articleOpen access

  Folate (vitamin B9) is involved in one-carbon transfer reactions and plays a significant role in nucleic acid synthesis and control of cellular proliferation, among other key cellular processes. It is now recognized that the role of folates in different stages of carcinogenesis is complex, and more research is needed to understand how folate reactions become dysregulated in cancers and the metabolic consequences that occur as a result. ALDH1L1 (cytosolic 10-formyltetrahydrofolate dehydrogenase), an enzyme of folate metabolism expressed in many tissues, is ubiquitously downregulated in cancers and is not expressed in cancer cell lines. The RT4 cell line (derived from papillary bladder cancer) which expresses high levels of ALDH1L1 represents an exception, providing an opportunity to explore the metabolic consequences of the loss of this enzyme. We have downregulated this protein in RT4 cells (shRNA driven knockdown or CRISPR driven knockout) and compared metabolomes of ALDH1L1-expressing and -deficient cells to determine if metabolic changes linked to the loss of this enzyme might provide proliferative and/or survival advantages for cancer cells. In this study, cell extracts were analyzed using Ultra High Performance Liquid Chromatography High Resolution Mass Spectrometry (UHPLC-HR-MS). A total of 13,339 signals were identified or annotated using an in-house library and public databases. Supervised and unsupervised multivariate analysis revealed metabolic differences between RT4 cells and ALDH1L1-deficient clones. Glycine (8-fold decrease) and metabolites derived from S-adenosylmethionine utilizing pathways were significantly decreased in the ALDH1L1-deficient clones, compared with RT4 cells. Other changes linked to ALDH1L1 downregulation include decreased levels of amino acids, Krebs cycle intermediates, and ribose-5-phosphate, and increased nicotinic acid. While the ALDH1L1-catalyzed reaction is directly linked to glycine biosynthesis and methyl group flux, its overall effect on cellular metabolism extends beyond immediate metabolic pathways controlled by this enzyme.

  PublisherDOI

• An untargeted metabolomic analysis of acute AFB1 treatment in liver, breast, and lung cells

  UNC Libraries · 2025-03-08

  articleOpen accessSenior author

  Aflatoxin B1 (AFB1) is a class 1 carcinogen and mycotoxin known to contribute to the development of hepatocellular carcinoma (HCC), growth impairment, altered immune system modulation, and malnutrition. AFB1 is synthesized by Aspergillus flavus and is known to widely contaminate foodstuffs, particularly maize, wheat, and groundnuts. The mechanism in which AFB1 causes genetic mutations has been well studied, however its metabolomic effects remained largely unknown. A better understanding of how AFB1 disrupts metabolism would provide insight into how this mycotoxin leads to carcinogenesis, growth impairment, and/or immunomodulation, and may reveal potential targets for pharmacological or nutritional interventions to protect against these effects. The current study evaluated the metabolomic effects of various doses (2.5 μM, 5 μM, 10uM) of AFB1 treatment to HepG2 (liver), MDA-MB-231 (breast), and A549 (lung) cells. Treated and control cells’ metabolomic profiles were evaluated via ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Univariate and multivariate analyses revealed significant alterations in metabolite concentrations from each dose of AFB1 treatment in each cell type. Pathway analysis was then used to understand broader biochemical functions affected by AFB1 treatment in each cell type. HepG2 cell pathway analyses revealed significant pathway perturbations in lipid metabolism, carnitine synthesis, catecholamine biosynthesis, purine metabolism, and spermidine and spermine biosynthesis. Analysis of A549 cells found a greater emphasis of perturbations on various amino acids along with lipid synthesis-related pathways, and catecholamine biosynthesis. Finally, analysis of treated MDA-MB-231 cells found spermidine and spermine biosynthesis, carnitine synthesis, plasma membrane-related pathways (phosphatidylcholine synthesis and alpha linolenic acid and linoleic acid metabolism), and various amino acid metabolism pathways to be most affected. These highlighted pathways should be targeted in future investigations to evaluate their potential in mitigating or preventing the development of negative health effects associated with AFB1 exposure.

  PublisherDOI

• Prenatal Organophosphate Pesticide Exposure and Targeted Maternal Pregnancy Metabolomic Profiles in the NYU CHES Cohort

  UNC Libraries · 2025-12-17

  articleOpen access1st authorCorresponding

  Prior research links prenatal exposure to organophosphate (OP) pesticides to adverse health outcomes via molecular mechanisms, such as oxidative stress, neurotransmitter disruption, and mitochondrial dysfunction. This study investigates such mechanisms by assessing the relationships between prenatal OP pesticide exposure and targeted urinary maternal metabolomic profiles using data from the New York University Children's Health and Environment Study (NYU CHES) cohort (<em>n</em> = 890). Urine samples were collected at three time points during pregnancy (<em>T</em>₁, <em>T</em>₂, <em>T</em>₃) and analyzed for six dialkyl phosphate (DAP) metabolites and a targeted set of 188 metabolites related to key biological functions. Associations between DAP concentrations and individual metabolites were estimated using linear and logistic regression models, with adjustment for potential confounders. Statistical analysis revealed significant associations between OP exposure and the studied maternal metabolomic profile, with the most associations observed during late pregnancy (<em>T</em>₃). The most robust associations across all models and time points were observed for acylcarnitine profiles, which were consistently altered in association with OP exposure. This study identifies specific metabolic signatures associated with OP pesticide exposure during pregnancy, providing insights into potential mechanisms of toxicity and implications for maternal and child health. Additional research is needed to validate these findings and further understand the functional significance of the identified metabolic disturbances.

  PublisherDOI

• Body Mass Index Modifies Associations Between Diet Quality and Circulating Metabolites: The CARDIA Study, 2005 to 2006

  Journal of the American Heart Association · 2025-09-30 · 1 citations

  articleOpen access

  BACKGROUND: Obesity perturbs metabolism, resulting in differential diet-disease associations, but metabolic pathways that differ by obesity remain unclear. We investigated whether cross-sectional associations between metabolites and diet quality differ by obesity status in 2832 participants in the CARDIA (Coronary Artery Risk Development in Young Adults) cohort study. METHODS: We used untargeted metabolomics (7255 metabolite peaks) and an a priori diet quality score (APDQS) to (1) compare model accuracy and prediction, stratified by body mass index (BMI); (2) assess modification of APDQS-metabolite associations by BMI in linear regression models; (3) identify pathways with differential metabolic activity by BMI; and (4) assess the strength and direction of associations with identified/annotated metabolites. RESULTS: =0.21). Of the 7255 metabolite peaks, 180 peaks were associated with APDQS and differed by BMI (false discovery rate<0.1). From pathway enrichment analyses, 6 pathways had differential metabolic activity by BMI (Fisher's exact test <0.05) including primary bile acid biosynthesis; steroid biosynthesis; steroid hormone biosynthesis; caffeine metabolism; valine, leucine, and isoleucine biosynthesis; linoleic acid metabolism. Strength of associations were strongest for those without overweight or obesity. CONCLUSIONS: Diet-metabolite associations were best detected among participants who did not have overweight/obesity. We identified associated diet-metabolic pathways that differ by obesity, suggesting potential metabolic-related mechanisms perturbed for those with obesity.

  PublisherDOI

• A Review of Metabolic Targets of Anticancer Nutrients and Nutraceuticals in Pre-Clinical Models of Triple-Negative Breast Cancer

  UNC Libraries · 2025-10-31

  articleOpen access

  Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is notoriously aggressive and has poorer outcomes as compared with other breast cancer subtypes. Due to a lack of targeted therapies, TNBC is often treated with chemotherapeutics as opposed to hormone therapy or other targeted therapies available to individuals with estrogen receptor positive (ER+) breast cancers. Because of the lack of treatment options for TNBC, other therapeutic avenues are being explored. Metabolic reprogramming, a hallmark of cancer, provides potential opportunities to target cancer cells more specifically, increasing efficacy and reducing side effects. Nutrients serve a significant role in metabolic processes involved in DNA transcription, protein folding, and function as co-factors in enzyme activity, and may provide novel strategies to target cancer cell metabolism in TNBC. This article reviews studies that have investigated how nutrients/nutraceuticals target metabolic processes in TNBC cells alone or in combination with existing drugs to exert anticancer effects. These agents have been shown to cause perturbations in many metabolic processes related to glucose metabolism, fatty acid metabolism, as well as autophagy and oxidative stress-related metabolism. With this information, we present the potential of nutrients as metabolism-directed anticancer agents and the potential for using these agents alone or in cocktails as a new direction for TNBC therapy.

  PublisherDOI

• Exploring the Contribution of (Poly)phenols to the Dietary Exposome Using High Resolution Mass Spectrometry Untargeted Metabolomics

  UNC Libraries · 2025-07-24

  articleOpen access

  SCOPE: This study presents a workflow to construct a Dietary Exposome Library (DEL) comprised of phytochemicals and their metabolites derived from host and gut microbiome metabolism for use in peak identification/annotation of untargeted metabolomics datasets. METHODS AND RESULTS: An evidence mapping initiative established target analytes related to the consumption of phytochemical-rich foods. Analytes were confirmed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS(n)) analysis of human biospecimens from dietary intervention studies of (poly)phenol-rich diets. One hundred and sixty six verified compounds were subsequently analyzed on an untargeted metabolomics platform to acquire chromatographic and high-resolution mass spectral data for construction of a DEL. The DEL facilitated identification/annotation of 123 metabolites associate with exposure to (poly)phenol enriched diets, which included aromatic ketones, benzoic acids, ellagic acids, caffeoylquinic acids, catecholamines, coumarins, hippuric acid, hydroxytoluenes, phenylamines, stilbenes, urolithins, valerolactones, and xanthonoids, in untargeted metabolomics datasets acquire from human plasma and urine reference materials. CONCLUSIONS: The DEL focusing on (poly)phenols and their metabolites of dietary exposure facilitated identification/annotation of ingested food components and their associated pathways in untargeted metabolomics datasets acquired from human biospecimens. The DEL continues to expand with the aim to provide evidence-based data for dietary metabolites in exposome research and inform the development of dietary intervention strategies.

  PublisherDOI

Recent grants

• NIH Grant U19ES019525

  NIH · $12.5M · 2017

• Animal Metabolism Phenotyping Core

  NIH · $11.3M · 1999–2027

• Mechanistic and metabolomic underpinnings of ALDH1L1 polymorphisms in the regulation of glycine metabolism

  NIH · $3.4M · 2021–2026

• NIH Grant R21GM075903

  NIH · $1.7M · 2010

• Eastern Regional Comprehensive Metabolomics Resource Core

  NIH · $20.1M · 2012–2019

Frequent coauthors

• Susan McRitchie

  166 shared

• Wimal Pathmasiri

  136 shared

• Blake R. Rushing

  University of North Carolina at Chapel Hill

  78 shared

• Timothy R. Fennell

  MRC Laboratory of Molecular Biology

  73 shared

• Delisha A. Stewart

  42 shared

• Shiying Wu

  38 shared

• Fengyu Zhang

  Hunan University of Traditional Chinese Medicine

  37 shared

• Jingquan Gao

  Lishui University

  36 shared

Awards & honors

• 2019 grant from the National Heart Lung and Blood Institute…
• PI of a grant funded through the National Institute of Gener…
• NIH Common Fund Eastern Regional Comprehensive Metabolomics…
• grant to develop new tools and conduct untargeted analysis f…
• award from NCI as the NIH Common Fund Metabolomics and Clini…