About

Tracy G. Anthony, Ph.D., is a professor in the Department of Nutritional Sciences at Rutgers University. She earned her B.S. in Human Nutrition and Foods from Virginia Tech, followed by M.S. and Ph.D. degrees in Nutritional Sciences from the University of Illinois. Dr. Anthony completed postdoctoral training in Cellular & Molecular Physiology at the Penn State College of Medicine in Hershey, PA. She has been recognized for her outstanding contributions to nutrition research, being the inaugural recipient of the Peter J. Reeds Young Investigator Award from the American Society for Nutrition (ASN) and receiving the prestigious Osborne and Mendel Award from ASN in 2023 for her basic research accomplishments in nutrition. Her professional interests include mentoring students and fostering their development into independent and successful individuals. Outside of her academic career, she enjoys spending time with her family, music, exercise, and has completed the Princeton HiTOPS Half-Marathon in 2019 and 2022.

Research topics

• Biology
• Endocrinology
• Internal medicine
• Medicine
• Chemistry
• Bioinformatics
• Biochemistry
• Computational biology
• Food science
• Immunology
• Ecology
• Genetics
• Pathology

Selected publications

• OGG1 increases exercise endurance via elevated skeletal muscle FGF21

  Journal of Biological Chemistry · 2026-03-10

  articleOpen access

  mice. Together with elevated circulating FGF21 levels and peripheral markers of FGF21 action, these data demonstrate a novel role for skeletal muscle OGG1 in modulating mitochondrial health and muscle endurance via FGF21 secretion and signaling.

  PublisherDOI

• An inhibitor of GCN2 and the integrated stress response directly targets ZAK protein kinase to limit cytotoxicity

  Journal of Biological Chemistry · 2026-04-01

  articleOpen access

  The integrated stress response (ISR) is a major mechanism protecting cells against environmental and physiological stresses. Central to the ISR is a collection of stress-sensing kinases, such as GCN2 (EIF2AK4). When nutrients are limiting or translating ribosomes stall or collide, activated GCN2 phosphorylates eIF2, lowering global protein synthesis, which conserves resources and confers targeted expression of stress-adaptive genes, such as the transcription factor ATF4. While beneficial during acute stress, chronic GCN2 activation can promote cancer progression and neurological disease, spurring the development of GCN2 inhibitors. However, achieving therapeutic specificity and understanding the pathological context of ISR modulation remains challenging and requires careful evaluation. One of the earliest and most widely used GCN2 inhibitors is GCN2iB. In this study, we report that GCN2iB is a direct inhibitor of the ZAK protein kinase, a critical upstream regulator of stress-activated MAPK signaling that functions in the ribotoxic stress response (RSR). Using biochemical measurements, cell-based assays, and structural modeling, we demonstrate that inhibition of ZAK by GCN2iB dampens stress-induced JNK and p38 activation, thereby masking the cytotoxic consequences normally associated with GCN2 inhibition. While suppression of GCN2 activity may be beneficial in specific disease models, concurrent inhibition of ZAK can negate these effects, obscure its therapeutic benefits, and lead to unanticipated phenotypes. These findings highlight the importance of assessing kinase selectivity in pharmacological studies of ISR modulation and emphasize that dual inhibition of GCN2 and ZAK can yield complex and context-dependent cellular responses.

  PublisherOA PDFDOI

• Impaired nitrogenous waste clearance promotes hepatocellular carcinoma

  Science Advances · 2026-01-09 · 2 citations

  articleOpen access

  In mammals, hepatic urea cycle enzymes (UCEs) convert ammonia, the toxic nitrogenous waste, into urea for excretion. In hepatocellular carcinoma (HCC), UCE expression is often heterogeneously repressed, but its role in tumorigenesis is unclear. We show that, as in patients, UCE expression is markedly reduced in multiple HCC mouse models, including those driven by oncogenic c-MET/β-catenin, leading to impaired ammonia clearance, altered amino acid metabolism, and increased pyrimidine synthesis. In contrast, UCE expression is largely preserved in c-MET/sgAxin1 tumors, allowing assessment of the consequences of UCE loss. Silencing individual UCEs increases ammonia burden and accelerates HCC with reprogrammed amino acid and pyrimidine metabolism, supporting a causal role for defective ammonia detoxification in oncogenesis. Notably, dietary protein restriction lowers hepatic ammonia and slows tumor growth. These findings establish a mechanistic link between nitrogen overload and hepatocarcinogenesis and highlight protein restriction as a feasible therapeutic strategy for patients with impaired nitrogenous waste handling.

  PublisherDOI

• Weight Loss During Obesity Provokes Asparaginase‐Associated Liver Steatosis and Endoplasmic Reticulum Stress

  The FASEB Journal · 2026-03-09

  articleOpen accessSenior authorCorresponding

  Asparaginase is an anti-leukemic agent that triggers severe adverse metabolic events. Obesity is a known risk factor for asparaginase-associated liver steatosis. To better understand why, we first compared the liver metabolome of lean versus diet-induced obese (DIO) mice exposed to native asparaginase and observed a substantially altered liver metabolome in DIO mice only. To explore the basis for the altered liver metabolome in DIO mice, we designed experiments to clarify the relative contributions of obesity versus feeding excessive fat during asparaginase on liver triglycerides. Lean mice and DIO mice were fed a high-fat, obesogenic diet (OD) or low fat, maintenance diet (MD) during exposure to pegylated (PEG)-asparaginase. In lean mice, feeding OD during PEG-asparaginase modestly (2-fold) increased liver steatosis. Obese mice fed OD during PEG-asparaginase showed the lowest food intake alongside the lowest liver triglyceride secretion rates, resulting in the largest (6-fold) increase in liver triglycerides and emergent endoplasmic reticulum (ER) stress. Switching obese mice to a MD during PEG-asparaginase did not rescue liver steatosis nor alleviate ER stress. In a separate study, DIO mice globally lacking albumin (AlbKO) were fed OD during exposure to PEG-asparaginase to examine if loss of the major plasma free fatty acid carrier could lessen liver steatosis, but loss of circulating albumin did not mitigate elevated liver triglycerides. In total, the results revealed that body weight loss enables asparaginase-associated liver steatosis and ER stress. Mitigating asparaginase-induced weight loss may be a meaningful strategy in preventing liver stress during treatment.

  PublisherDOI

• A metabolic basis for motor deficits in mice lacking BCKDK

  The Journal of Nutritional Biochemistry · 2026-01-24

  articleSenior authorCorresponding
  PublisherDOI

• A metabolic basis for motor deficits in mice lacking BCKDK

  Rutgers University Community Repository (Rutgers University) · 2025-01-01

  otherOpen access
  PublisherDOI

• Off-target depletion of plasma tryptophan by allosteric inhibitors of BCKDK

  Molecular Metabolism · 2025-05-08 · 2 citations

  articleOpen access

  The activation of branched chain amino acid (BCAA) catabolism has garnered interest as a potential therapeutic approach to improve insulin sensitivity, enhance recovery from heart failure, and blunt tumor growth. Evidence for this interest relies in part on BT2, a small molecule that promotes BCAA oxidation and is protective in mouse models of these pathologies. BT2 and other analogs allosterically inhibit branched chain ketoacid dehydrogenase kinase (BCKDK) to promote BCAA oxidation, which is presumed to underlie the salutary effects of BT2. Potential “off-target” effects of BT2 have not been considered, however. We therefore tested for metabolic off-target effects of BT2 in Bckdk -/- animals. As expected, BT2 failed to activate BCAA oxidation in these animals. Surprisingly, however, BT2 strongly reduced plasma tryptophan levels and promoted catabolism of tryptophan to kynurenine in both control and Bckdk -/- mice. Mechanistic studies revealed that none of the principal tryptophan catabolic or kynurenine-producing/consuming enzymes (TDO, IDO1, IDO2, or KATs) were required for BT2-mediated lowering of plasma tryptophan. Instead, using equilibrium dialysis assays and mice lacking albumin, we show that BT2 avidly binds plasma albumin and displaces tryptophan, releasing it for catabolism. These data confirm that BT2 activates BCAA oxidation via inhibition of BCKDK but also reveal a robust off-target effect on tryptophan metabolism via displacement from serum albumin. The data highlight a potential confounding effect for pharmaceutical compounds that compete for binding with albumin-bound tryptophan. • BT2, an inhibitor of BCKDK with analogs currently in clinical development, has off-target metabolic effects • Treating mice with BT2 dramatically lowers plasma levels of tryptophan even in the absence of BCKDK • Most plasma tryptophan is bound to albumin • BT2 avidly binds to albumin and displaces tryptophan, thereby lowering plasma tryptophan levels

  PublisherDOI

• Branched chain amino acid sufficiency is necessary for proper luteinizing hormone response and testosterone synthesis

  Reproductive Biology · 2025-10-31 · 1 citations

  articleOpen accessCorresponding

  Testosterone production by testicular Leydig cells (steroidogenesis) is vital to male fertility and overall male health. Information about how nutrition influences Leydig cell steroidogenesis is lacking. Branched chain amino acids (BCAAs - leucine, isoleucine, and valine) are essential amino acids and important regulators of protein synthesis and energy production. Circulating and tissue BCAA levels are tightly regulated by the enzyme branched chain a-keto acid dehydrogenase kinase (BCKDK), which inhibits their catabolism. This work explored how BCAAs, and especially leucine, modulate male fertility and testosterone production. In a mutant mouse model of Bckdk, breeding analysis showed reduced male fertility and circulating testosterone. Further, morphological evaluation demonstrated testicular and epididymal abnormalities consistent with abnormal testicular androgen signaling. Fertility was partially rescued by feeding a high protein diet while circulating testosterone was not. In wild type testes, Leydig cells were the primary cell type to express BCKDK. Leveraging a primary interstitial cell culture, cell survival and apoptosis analyses demonstrated Leydig cells are highly sensitive to leucine deprivation and this sensitivity is enhanced under steroidogenesis stimulating conditions. Lastly, using the same primary cell culture system, testosterone production was shown to be lost under leucine deprivation. In total, this work demonstrates Leydig cells are uniquely sensitive to BCAA status under steroidogenesis stimulation and that regulated BCAA catabolism may be important for optimal male fertility.

  PublisherDOI

• Autophagy-related 7 (ATG7) regulates food intake and liver health during asparaginase exposure

  Journal of Biological Chemistry · 2025-01-10 · 6 citations

  articleOpen accessSenior author

  Amino acid starvation by the chemotherapy agent asparaginase is a potent activator of the integrated stress response (ISR) in the liver and can upregulate autophagy in some cell types.We hypothesized that autophagy-related 7 (ATG7), a protein that is essential for autophagy and an ISR target gene, was necessary during exposure to asparaginase to maintain liver health.We knocked down Atg7 systemically (Atg7 D/D ) or in hepatocytes only (ls-Atg7KO) in mice before exposure to pegylated asparaginase for 5 days.Intact mice injected with asparaginase lost body weight due to reduced food intake and increased energy expenditure.Systemic Atg7 ablation reduced liver protein synthesis and increased liver injury in vehicle-injected mice but did not further reduce liver protein synthesis, exacerbate steatosis or liver injury, or alter energy expenditure following 5 days of asparaginase exposure.Atg7 D/D mice were unexpectantly protected from asparaginase-induced anorexia and weight loss.This protection corresponded with reduced phosphorylation of hepatic GCN2 and blunted increases in ISR gene targets including growth differentiation factor 15 (GDF15), a negative regulator of food intake.Interestingly, asparaginase elevated serum GDF15 and reduced food intake in ls-Atg7KO mice, similar to intact mice.Liver triglycerides and production of the hepatokine fibroblast growth factor 21, another ISR gene target, were suppressed in asparaginase-exposed Atg7 D/D and ls-Atg7KO mice.This work identifies a bidirectional relationship between autophagy and the ISR in the liver during asparaginase, affecting food intake and liver health.

  PublisherOA PDFDOI

• Deletion of hepatic FXR leads to more severe MASH development in female mice.

  PubMed · 2025-06-01 · 2 citations

  articleOpen access

  BACKGROUND: The farnesoid X receptor (FXR) has been identified as a therapeutic target for metabolic dysfunction-associated steatohepatitis (MASH). FXR is the major homeostatic regulator of bile acids (BAs) with dysregulation of BAs and/or FXR implicated in the pathogenesis of MASH. Synthetic whole-body FXR agonists have been developed to treat MASH. Although beneficial for MASH treatment, these whole-body modulators contribute to unfavorable side effects such as pruritus and an elevation in low-density liporoteins, thereby highlighting the importance of tissue and cell-restricted modulation of FXR in the development of novel therapeutics for MASH to negate potential harmful off-target effects. METHODS: The objective of this study was to determine the tissue-specific role of FXR in MASH development using male and female wild-type (WT), liver FXR KO (FXRhep-/-), intestinal FXR KO (FXRint-/-), and whole body FXR KO (FXR KO) mice fed either a low-fat control diet (CTL) or a MASH "Fast Food" (FF) diet. RESULTS: The results showed, in females, hepatic, but not intestinal, deficiency of FXR was associated with severe liver injury, through increased ALT, ALP, and genes indicative of inflammation and fibrosis when comparing FXRhep-/- versus FXRint-/-. Regardless of sex, hepatic FXR deficiency triggered the activation of neuroinflammation and neurodegenerative canonical pathways. CONCLUSIONS: These data suggest that hepatic FXR is more critical in suppressing liver injury during MASH development in female mice. However, this same trend was not clear in the male cohorts, highlighting sex differences and potential roles for sexual dimorphism in MASH development.

  PublisherOA PDFDOI

Recent grants

• Molecular Mechanisms of Adverse Metabolic Events by Asparaginase.

  NIH · $1.9M · 2011–2017

• Homeostatic Responses to Amino Acid Insufficiency

  NIH · $5.4M · 2016–2026

Frequent coauthors

• Ronald C. Wek

  Indiana University School of Medicine

  174 shared

• Donald K. Layman

  University of Illinois Urbana-Champaign

  100 shared

• Sean H. Adams

  University of California, Davis

  85 shared

• Blake B. Rasmussen

  82 shared

• Christopher J. Lynch

  Syracuse University

  82 shared

• Teresa A. Davis

  Children's Nutrition Research Center at Baylor College of Medicine

  81 shared

• Grant D. Brinkworth

  81 shared

• Piyawan Bunpo

  Chiang Mai University

  79 shared

Labs

• The Anthony labPI

Education

• B.S., Human Nutrition and Foods

  Virginia Tech University

• M.S., Nutritional Sciences

  University of Illinois at Urbana-Champaign

• Ph.D., Nutritional Sciences

  University of Illinois at Urbana-Champaign

• Other, Cellular and Molecular Physiology

  Penn State College of Medicine at Hershey