About

Dr. Blake Rushing is an Assistant Professor at the University of North Carolina at Chapel Hill’s Nutrition Research Institute (NRI). His lab applies multi-omics approaches, including analytical chemistry techniques such as liquid chromatography-mass spectrometry, to investigate the metabolic mechanisms underlying cancer and other chronic, age-related diseases. His research focuses on how nutrient metabolism can inform disease progression, therapy resistance mechanisms, and biomarker development. Currently, Dr. Rushing leads pan-cancer projects that integrate metabolomics with genomics, transcriptomics, proteomics, and lipidomics to identify dysregulation of nutrient metabolism across different cancer types and its links to genetic features. These efforts aim to advance precision oncology by uncovering new pharmacological and nutritional strategies for cancer prevention, detection, and treatment.

Research topics

• Biology
• Chemistry
• Biochemistry
• Genetics
• Bioinformatics
• Medicine
• Chromatography
• Computational biology
• Physiology
• Microbiology
• Cell biology
• Obstetrics
• Internal medicine
• Pathology

Selected publications

• Abstract 2027: ATP citrate lyase fuels lipid storage to support triple negative breast cancer chemoresistance.

  Cancer Research · 2026-04-03

  article

  Abstract Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype in which neoadjuvant chemotherapy (NACT) is the backbone of standard of care. Unfortunately, ∼45% of patients have residual tumor burden following NACT, which is strongly associated with poor prognoses. Our group previously demonstrated that mitochondrial oxidative phosphorylation is upregulated and is a therapeutic vulnerability of chemo-refractory TNBC. We used metabolomic flux tracing to show a heightened contribution of glucose oxidation to the tricarboxylic acid (TCA) cycle in residual human TNBC cells surviving several conventional chemotherapies. We found significantly elevated abundance of citrate and acetyl-coA (AcCoA) in residual cells. Further, glucose, but not palmitate, glutamine, or acetate, derived heavy carbon was more strongly incorporated into citrate and AcCoA in residual relative to naïve cells. Concomitantly, we observed drastic lipidomic remodeling, largely characterized by elevation of triglycerides, long chain fatty acids, and poly unsaturated fatty acids (PUFAs) in cultured TNBC cells and orthotopic patient-derived xenograft (PDX) tumors following chemotherapy relative to their treatment naïve counterparts. This was accompanied by a significant increase in the number of lipid droplets (LDs) in residual cells. Together, these data suggest glucose oxidation supports fatty acid synthesis (FAS) and storage in chemoresistant TNBC. Our analyses of human TNBC proteomic and transcriptomic data affirmed the significant association of fatty acid metabolism with TNBC chemoresistance, as well as its upregulation in chemotherapy-treated tumors relative to their pre-treated counterparts. Mining those data led us to ATP citrate lyase (ACLY), the rate limiting enzyme for cytosolic AcCoA production from citrate. We hypothesized that ACLY converts excess citrate, generated by heightened TCA cycling, to AcCoA to promote FAS and storage in chemoresistant TNBC. We found elevated protein levels of ACLY and an activating phosphorylation mark in TNBC cells surviving treatment with conventional chemotherapies doxorubicin and carboplatin. ACLY knockdown or inhibition potently reduced chemotherapy-induced accumulation of AcCoA and LDs and elicited lipidomic rewiring largely characterized by increased PUFAs. Notably, combining ACLY inhibition or KD with conventional chemotherapy treatments provided significant improvement of tumor cell growth inhibition. These data indicate that NACT can cause accumulation of citrate, AcCoA, LDs, and overall lipidomic rewiring through ACLY. ACLY is a novel functional dependency of chemo-refractory TNBC and should be further explored as a potential therapeutic target. We posit that TNBC cells adapt to the stress of NACT by upregulating lipid synthesis and storage in conjunction with glucose catabolism, enhancing metabolic flexibility and cell survival. Citation Format: Katherine E. Pendelton, Mokryun L. Baek, Mariah J. Berner-Wu, Steven W. Wall, Audra Lane, Jonathan T. Lei, Iqbal Mahmud, Lin Tan, Lacey E. Dobrolecki, Philip L. Lorenzi, Michael T. Lewis, Blake R. Rushing, Gloria V. Echeverria. ATP citrate lyase fuels lipid storage to support triple negative breast cancer chemoresistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2027.

  PublisherDOI

• Newborn metabolomic perturbations associated with prenatal tobacco smoke exposure and early birth

  Communications Medicine · 2026-04-01

  articleOpen access

  BACKGROUND: Exposure to tobacco smoke during pregnancy is an established risk factor for early birth including early term birth (ETB) and preterm birth (PTB). However, the underlying molecular mechanisms are minimally understood. In this study, we aimed to characterize the newborn metabolomic associations with early pregnancy maternal tobacco exposure biomarkers and early birth in 269 mother-child pairs in the Atlanta African American Maternal-Child Cohort (2016-2020). METHODS: Established tobacco exposure biomarkers, cotinine and trans-3'-hydroxycotinine (3HC), were measured in maternal urine samples collected between 8-14 weeks of gestation. Newborn dried blood spots were collected for high-resolution metabolomics profiling. Metabolome-wide association studies and pathway enrichment analyses were conducted to determine metabolomic signals and pathways associated with tobacco exposure biomarkers, ETB, and PTB. RESULTS: We show that biopterin metabolism is a significantly enriched pathway for all exposures and outcomes. Both tobacco exposure biomarkers are associated with riboflavin metabolism. The metabolites riboflavin and 5-hydroxytryptophan are associated with all exposures and outcomes. CONCLUSIONS: Taken together, these findings demonstrate that the newborn metabolome is altered by prenatal tobacco exposure and that these alterations are associated with elevated risks of early birth. Furthermore, perturbation in biopterin metabolism is a potential mechanism linking maternal tobacco exposure to early birth.

  PublisherOA PDFDOI

• Integration of metabolomic and genetic data reveals novel variants underpinning the human metabolome: the Coronary Artery Risk Development in Young Adults (CARDIA) study

  medRxiv · 2026-01-30

  articleOpen access

  ABSTRACT Metabolite genome-wide association studies have identified hundreds of variants, many of which play intermediate roles linking genotype and phenotype with downstream diseases. However, the majority of metabolite GWAS have been published in self-identified Non-Hispanic White (NHW) populations, greatly limiting inference to other populations. Here we report the results of a GWAS of 7,522 untargeted metabolite peaks in 2,183 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study (714 Black and 1,469 White individuals, mean age = 43.56, women = 56.1%). We performed untargeted metabolomic profiling on plasma samples from these individuals using ultra-high performance liquid chromatography-high resolution mass spectrometry. Using race/ethnicity-stratified and combined GWAS of 8,534,915 (Black stratum) and 5,886,255 (White stratum) common variants (minor allele frequency ≥ 0.05) from TOPMed Imputation Reference Panel r 2 , we examined association with the CARDIA 7,522 metabolite peaks. We used MetaboAnalyst 5.0 and publicly available phenome-wide association studies to predict functional pathway activity and characterize unknown peaks. We identified 171 significant ( P -value < 6.6×10 -13 ) sentinel variants across 536 metabolite peaks, of which 39 were annotated with our in-house library in the race-combined CARDIA analysis. PheWAS and pathway enrichment models provided information on unannotated metabolite peaks including the novel KHNYN/SDR39U1 locus which supports vitamin B5’s involvement in the citric acid cycle. We also identified a race-specific variant (rs79530723) near SLC28A1 , which plays an important role in cytidine metabolism and was specific to the CARDIA Black participants. Pathway analyses prioritized a role of pyrimidine metabolism for this peak, a finding supported by studies in the Hispanic/Latino populations. Overall, our study results support a strong shared genetic architecture of the human metabolome across diverse populations and reveal new metabolite GWAS signals, underscoring the value of integrating ‘omics’ techniques to enhance comprehension of its genetic architecture.

  PublisherOA PDFDOI

• Sex Modifies Metabolic Pathways Associated with Lipids in Untargeted Metabolomics: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, 2005–2006

  UNC Libraries · 2025-12-03

  articleOpen access

  Background: There are differences in lipid metabolism by sex that are relevant for health, but metabolic pathways are not fully understood. We investigated sex differences in cross-sectional associations between metabolic pathways identified using untargeted metabolomics and clinical lipid measures (total cholesterol [TC], triglycerides [TG], and low- and high-density lipoprotein cholesterol [LDL-c; HDL-c]) from blood plasma in the Coronary Artery Risk Development in Young Adults (CARDIA) study (Year 20; 2005–2006). Our objective was to determine whether associations between metabolic pathways and lipid measures differ by sex and to identify pathways that may underlie sex-specific mechanisms of lipid metabolism. Methods: Using data from 2169 participants, (44% women, mean age = 45, 58% White, 42% Black), we used: (1) Orthogonal partial least squares-regression (OPLS-R) to compare variation in TC, TG, LDL-c, and HDL-c explained by metabolites in men vs. women, (2) linear regression to assess sex-modification of associations between 7255 metabolite peaks and lipid measures using false discovery rate (FDR)-corrected p < 0.1, and (3) pathway enrichment analyses to identify metabolic pathways that differed by sex using Fisher’s exact test (FET) p < 0.05. Results: We found that: (1) untargeted metabolomic data reflected variation in lipid measures better for men compared to women, (2) associations between metabolite peaks and lipid measures differed by sex, and (3) 8 unique pathways differed by sex, particularly primary bile acid biosynthesis, linoleic acid metabolism, and arginine biosynthesis. Conclusions: Our findings suggest distinct lipid-associated metabolic activity by sex that points to potential mechanistic pathways.

  PublisherDOI

• Metabolomic Signatures of Physical Function and Functional Trajectories in Older Adults: Insights from the ENRGISE Clinical Trial

  Metabolites · 2025-12-22

  articleOpen access

  Background: Chronic inflammation contributes to functional decline in older adults, yet interventions targeting inflammatory pathways have shown inconsistent results. Metabolomics offers a promising approach to identify biological heterogeneity and uncover molecular signatures underlying differential functional trajectories. Objective: Our objective was to examine whether untargeted serum metabolomics can identify metabolic signatures associated with baseline physical function, functional trajectories, and treatment response in older adults with chronic inflammation participating in the ENRGISE trial. Methods: We performed untargeted metabolomic profiling on serum samples (n = 731) collected at baseline, 6, and 12 months from participants (mean age ≥ 70) enrolled in the ENRGISE pilot randomized trial. Participants were randomized to losartan, omega-3 supplementation, both, or placebo. Functional measures included grip strength and 400 m gait speed. Group-based trajectory modeling classified participants into functional trajectories over 12 months. Partial least squares-discriminant analysis (PLS-DA) and pathway enrichment (mummichog algorithm) were used to identify differentially abundant metabolites and perturbed pathways. Results: Baseline metabolomic profiles differed by physical function status. Participants with low grip strength showed enrichment in vitamin A metabolism pathways, while slower gait speed was associated with higher levels of prostaglandin and eicosanoid metabolites. Baseline metabolic profiles distinguished individuals who later declined versus improved in functional performance. Omega-3 supplementation, but not losartan, induced distinct changes in lipid-related pathways, including fatty acid activation, omega-3 metabolism, and prostaglandin biosynthesis, indicating that individuals responded to these interventions metabolically despite null clinical outcomes. Conclusions: Serum metabolomic signatures were associated with baseline physical function, predicted functional trajectories, and revealed pharmacologic activity of omega-3 supplementation. These findings support the use of metabolomics to uncover biological heterogeneity and inform precision geroscience strategies in aging populations.

  PublisherOA PDFDOI

• 799 Dissecting the role of folate receptor beta-mediated one-carbon metabolism in tumor-associated macrophages

  Regular and Young Investigator Award Abstracts · 2025-11-01

  articleOpen access
  PublisherOA PDFDOI

• 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 accessSenior author

  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

• 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

• Pemmican Supplementation Linked to Beneficial Metabolite Signature in Marines During Cold Weather Operations Training

  Current Developments in Nutrition · 2025-05-01 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Efficacy and feasibility of preoperative high-intensity interval training in endometrial cancer patients

  Gynecologic Oncology · 2025-09-01

  article
  PublisherDOI

Frequent coauthors

• Susan Sumner

  University of California, Los Angeles

  78 shared

• Susan McRitchie

  43 shared

• Wimal Pathmasiri

  35 shared

• David C. Nieman

  Appalachian State University

  20 shared

• Camila A. Sakaguchi

  Appalachian State University

  20 shared

• Mansi Choudhari

  David H. Murdock Research Institute

  18 shared

• Sergey A. Krupenko

  University of North Carolina at Chapel Hill

  17 shared

• Michael J. Thompson

  17 shared

Labs

• Nutritional Research Institute (NRI) Metabolomics and Exposome LaboratoryPI

Education

• Graduate Student, Pharmacology & Toxicology

  East Carolina University

Awards & honors

• Emerging Leader Award in Metabolomics Service Cores 2024
• Research Development Award, 2023
• NRI Pilot and Feasibility (P&F) Award 2022