About

Professor Grace Guo is associated with EOHSI at Rutgers University, which sponsors research, education, and service programs in environmental health, toxicology, occupational health, exposure assessment, public policy, and health education. The institute houses a group of scientists, physicians, educators, and policy researchers engaged in studies of contaminants and various environmental policy and public health issues. EOHSI's mission includes studying and improving environmental and occupational health through scientific research, training, and communication of research findings to professional and lay groups. While specific details about Professor Guo's individual research focus, background, or key contributions are not provided in the page text, her association with EOHSI indicates her involvement in these areas of environmental health and related studies.

Research topics

• Biology
• Medicine
• Endocrinology
• Internal medicine
• Computer Science
• Biochemistry
• Chemistry
• Biotechnology
• Cancer research
• Risk analysis (engineering)
• Pharmacology
• Computational biology

Selected publications

• Human pegivirus co-infection in SARS-CoV-2: Prevalence and clinical associations

  Next research. · 2026-02-12

  articleOpen access

  • Systematic screening of human pegivirus (HPgV), an unmonitored viral co-infection, in COVID-19 (N = 634). • HPgV prevalence in COVID-19 mirrored population estimates but was markedly enriched in HIV (positive control). • HPgV-positive COVID-19 cases showed trends toward milder clinical outcomes. • Findings highlight the potential relevance of immunomodulatory viral co-infections in SARS-CoV-2 infection. This study investigates the prevalence of human pegivirus (HPgV) in SARS-CoV-2-positive patients within the context of viral co-infections that may modulate COVID-19 outcomes and assesses whether HPgV co-infection is associated with COVID-19 severity. HPgV is a widely circulating but rarely monitored human virus with documented immunomodulatory effects in other viral infections, including HIV and Ebola. While HPgV prevalence is low in the general U.S. population (1–2%), it rises markedly in the setting of chronic viral co-infections, particularly HIV (15–40%). Given its immunologic effects and persistence, HPgV represents a biologically plausible but unexplored viral co-factor SARS-CoV-2 infection. Methods : We analyzed four cohorts: SARS-CoV-2–positive individuals, ICU patients with respiratory symptoms but SARS-CoV-2–negative, HIV-positive individuals as a positive control for HPgV detection, and uninfected controls. Results : HPgV prevalence in COVID-19 patients was low (2.1%) and comparable to population estimates. As expected, HPgV prevalence was substantially higher in the HIV cohort (34%), validating assay performance and cohort stratification. Among HPgV-positive COVID-19 cases, most experienced mild disease, with directional trends toward reduced severity despite high baseline risk factors. Healthcare workers in the control group showed unexpectedly elevated HPgV prevalence (9.6%). Conclusions : HPgV is an unmonitored but widely circulating viral co-infection in humans that may influence host responses to SARS-CoV-2. Although limited by small numbers, these findings are descriptive and hypothesis-generating, supporting further investigation of HPgV and other immunomodulatory viral co-infections in COVID-19. Larger studies will be required to determine whether the observed patterns are reproducible and clinically meaningful.

  PublisherDOI

• Viral Co-infection in COVID-19: Prevalence and Clinical Associations of Human Pegivirus

  medRxiv · 2026-02-09

  articleOpen access

  Objective: This study investigates the prevalence of human pegivirus (HPgV) in SARS-CoV-2-positive patients within the context of viral co-infections that may modulate COVID-19 outcomes and assesses whether HPgV co-infection is associated with COVID-19 severity. HPgV is a widely circulating but rarely monitored human virus with documented immunomodulatory effects in other viral infections, including HIV and Ebola. While HPgV prevalence is low in the general U.S. population (1-2%), it rises markedly in the setting of chronic viral co-infections, particularly HIV (15-40%). Given its immunologic effects and persistence, HPgV represents a biologically plausible but unexplored viral co-factor SARS-CoV-2 infection. Methods: We analyzed four cohorts: SARS-CoV-2-positive individuals, ICU patients with respiratory symptoms but SARS-CoV-2-negative, HIV-positive individuals as a positive control for HPgV detection, and uninfected controls. Results: HPgV prevalence in COVID-19 patients was low (2.1%) and comparable to population estimates. As expected, HPgV prevalence was substantially higher in the HIV cohort (34%), validating assay performance and cohort stratification. Among HPgV-positive COVID-19 cases, most experienced mild disease, with directional trends toward reduced severity despite high baseline risk factors. Healthcare workers in the control group showed unexpectedly elevated HPgV prevalence (9.6%). Conclusions: HPgV is an unmonitored but widely circulating viral co-infection in humans that may influence host responses to SARS-CoV-2. Although limited by small numbers, our findings support further investigation of HPgV and other immunomodulatory viral co-infections in COVID-19. This study suggests that HPgV co-infection may influence COVID-19 outcomes, warranting further investigation. Highlights: Systematic screening of human pegivirus (HPgV), an unmonitored viral co-infection, in COVID-19 (n = 634).HPgV prevalence in COVID-19 mirrored population estimates but was markedly enriched in HIV (positive control).HPgV-positive COVID-19 cases showed trends toward milder clinical outcomes.Findings highlight the potential relevance of immunomodulatory viral co-infections in SARS-CoV-2 infection. Executive Summary: This study evaluated the prevalence of human pegivirus (HPgV) co-infection among SARS-CoV-2-positive patients as part of a broader effort to understand how concurrent viral infections may influence COVID-19 severity. HPgV is a largely unmonitored, persistent human virus with well-described immunomodulatory effects in other viral infections, yet it has not been systematically evaluated in COVID-19. We therefore screened HPgV prevalence across COVID-19 cases, comparator cohorts, and an HIV-positive cohort as a positive control due to the well-established high prevalence of HPgV in HIV infection. Our findings indicate that HPgV prevalence in SARS-CoV-2-positive and -negative hospitalized individuals are consistent with the general U.S. population range (approximately 1-5%). Healthcare professionals exhibited a higher HPgV prevalence (∼10%), suggesting that repeated occupational viral exposures may influence infection rates. While limited by small numbers, HPgV co-infection in COVID-19 cases was associated with directional trends toward reduced disease severity, warranting further longitudinal and mechanistic investigation. Editor’s summary: This study identifies human pegivirus as a widely circulating, unmonitored viral co-infection in COVID-19 with potential relevance to disease severity.

  PublisherOA PDFDOI

• Ursodeoxycholic acid acts as an ileal FXR agonist in male mice with hepatic deficiency of FXR

  eGastroenterology · 2025-07-01 · 3 citations

  articleOpen accessSenior author

  Background Farnesoid X receptor (FXR) has been identified as a therapeutic target for metabolic dysfunction-associated steatohepatitis (MASH). Hepatic FXR is especially critical in suppressing liver inflammation. FXR agonism and antagonism have both proven to be beneficial in the mitigation of MASH, leading to much controversy in the field, particularly regarding FXR signalling in the gut. The objective of this study was to determine the effects of ursodeoxycholic acid (UDCA), a postulated gut FXR antagonist with liver protective effects, on the mitigation and prevention of MASH development in mice with hepatic FXR deficiency. Methods For this experiment, six-week-old to eight week-old male and female liver-specific FXR knockout (FXR hep-/- ) and control (FXR hep flox/flox ) mice were fed either a low-fat control diet (CTL) or a MASH ‘Fast Food’ diet (Western diet with 21% milk fat, 1.25% cholesterol and 34% sucrose) both supplemented with or without 0.1% (weight/weight; w/w) UDCA for 16 weeks. Results UDCA feeding tended to reduce alanine aminotransferase levels and decrease liver lipids in the male mice. Supplementation of UDCA showed a trend towards increased UDCA and tauroursodeoxycholic acid (TUDCA) levels in serum, liver and intestine, although the male mice displayed more than twice the amount of these bile acids compared with the female mice. CTL-UDCA feeding resulted in a significant induction of Fxr and Fgf15 mRNA expression in the ileum of the male mice. Conclusion The data strongly suggest that UDCA seems to act as an FXR agonist, especially in the ileum, which contrasts with previous reports that UDCA acts as a gut FXR antagonist. In addition, UDCA seems to be exerting liver protective effects predominantly in the male mice.

  PublisherOA PDFDOI

• Mutation of PXR phosphorylation motif at Ser347 disrupts lipid and bile acid homeostasis in diet-induced metabolic dysfunction–associated steatohepatitis in mice

  Drug Metabolism and Disposition · 2025-12-22

  articleOpen accessSenior author

  The pregnane X receptor (PXR), a ligand-activated transcription factor, regulates the expression of genes involved in endobiotic and xenobiotic metabolism, inflammation, and fibrosis. Disruption of PXR functions can affect processes critical to metabolic dysfunction-associated steatohepatitis (MASH) progression. Although ligand-dependent PXR functions are well studied, its regulation by post-translational modification, particularly phosphorylation, remains unclear. PXR has a conserved phosphorylation motif within its ligand binding domain (Ser347 in mice; Ser350 in humans). In vitro studies showed that this site mutation impairs human PXR transcriptional activity; however, the mechanism remains elusive. To investigate this phosphorylation site role in MASH development, wild-type and PXR Ser347Ala knock-in mutation (PXR-KI) mice were fed either a high-fat diet or a control chow diet for 16 weeks. On control chow diet, PXR-KI mice exhibited decreased expression of alternative bile acid (BA) synthesis genes compared with wild-type mice. On a high-fat diet, PXR-KI mice manifested more severe hepatic steatosis, revealed by elevated serum total cholesterol, and increased expression of genes involved in lipid metabolism. In addition, changes in BA metabolism and transporter genes suggested a cholestatic pattern in this group of mice. BA profiling showed higher levels of conjugated, hydrophilic, primary BA in the serum and liver, and increased unconjugated BA in the intestine. The data suggest that PXR Ser347 phosphorylation motif is essential for regulating PXR functions to maintain endobiotic metabolism and alleviate hepatotoxicity during MASH progression. SIGNIFICANT STATEMENT: The ligand-independent role of pregnane X receptor (PXR) is unclear. In phosphodeficient PXR knock-in mice, loss of Ser347 phosphorylation worsened hepatic steatosis and altered bile acid homeostasis under high-fat diet feeding, uncovering a novel role and therapeutic potential of PXR phosphorylation in fatty liver diseases.

  PublisherDOI

• Fibroblast growth factor 15 overexpression and combined peroxisome proliferator–activated receptor α activation attenuates metabolic dysfunction–associated steatohepatitis progression in mice

  Drug Metabolism and Disposition · 2025-07-25

  articleOpen accessSenior author

  Metabolic dysfunction-associated steatohepatitis (MASH) is increasing worldwide along with the obesity epidemic. However, there are limited treatments. Fibroblast growth factor (FGF)19 and its mouse ortholog FGF15, act as hormones to repress bile acid synthesis and increase energy expenditure. Activation of peroxisome proliferator-activated receptor (PPAR)α increases fatty acid oxidation in hepatocytes. However, a combined role of FGF19/15 with activation of PPARα in the treatment of MASH is unknown. Wild-type and Fgf15 transgenic (Fgf15 Tg) mice were fed a high-fat diet (HFD) to induce MASH, then a PPARα agonist was subsequently administered to a subcohort of HFD groups to study the synergistic effect of Fgf15 overexpression and PPARα activation. HFD feeding diminished glucose tolerance and increased liver fat accumulation in both wild-type and Fgf15 Tg mice. However, Fgf15 Tg mice demonstrated resistance to weight gain, displayed improved glucose tolerance, and attenuated liver steatosis. Fgf15 overexpression alone reduced liver injury and the expression of genes involved in inflammation and fibrosis. The activation of PPARα, both individually and in conjunction with FGF15 overexpression, led to weight loss and reduced liver steatosis. However, the combined approach with PPARα activation and FGF15 overexpression resulted in an increase in liver injury and upregulation of gene expression associated with inflammation and fibrosis. In summary, Overexpression of FGF15 alone, with or without a combined activation of PPARα, effectively reduces hepatic steatosis. However, the combined treatment leads to increased oxidative stress and ductular reactions, indicating a complex interplay in the pathogenesis of MASH. SIGNIFICANCE STATEMENT: Fibroblast growth factor (FGF)15 overexpression and peroxisome proliferator-activated receptor (PPAR)α activation ameliorates high-fat diet-induced hepatic steatosis. Combined PPARα activation and FGF15 overexpression exacerbated high-fat diet-induced liver injury and inflammation. Overexpression of FGF15 alone or combination with PPARα activation induced antioxidant response and ductular reactions.

  PublisherDOI

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

  PubMed · 2025-06-01 · 2 citations

  articleOpen accessSenior author

  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

• Dual Effects of Maternal Diet and Perinatal Organophosphate Flame Retardant Treatment on Offspring Development, Behavior and Metabolism

  Toxics · 2025-07-29 · 2 citations

  articleOpen access

  The maternal-fetal environment is influenced by multiple factors, including nutrition and environmental contaminants, which can impact long-term development. Perinatal exposure to organophosphate flame retardants (OPFRs) disrupts energy homeostasis and causes maladaptive behaviors in mice. Maternal obesity affects development by impairing blood-brain barrier (BBB) formation, influencing brain regions involved in energy regulation and behavior. This study examined the combined effects of maternal obesity and perinatal OPFR treatment on offspring development. Female mice were fed either a low-fat (LFD) or a high-fat diet (HFD) for 8 weeks, mated, and treated with either sesame oil or an OPFR mixture (tris(1,3-dichloro-2-propyl)phosphate, tricresyl phosphate, and triphenyl phosphate, 1 mg/kg each) from gestational day 7 to postnatal day 14. Results showed that both maternal diet and OPFR treatment disrupted blood-brain barrier integrity, energy balance, and reproductive gene expression in the hypothalamus of neonates. The expression of hepatic genes related to lipid and xenobiotic metabolism was also altered. In adulthood, LFD OPFR-treated female offspring exhibited increased avoidance behavior, while HFD OPFR-treated females demonstrated memory impairments. Metabolic assessments revealed decreased energy expenditure and nighttime activity in LFD OPFR-treated females. These findings suggest that maternal diet and OPFR treatment alter hypothalamic and liver gene expression in neonates, potentially leading to long-term metabolic and behavioral changes.

  PublisherOA PDFDOI

• Intestinal Stearoyl-CoA Desaturase-1 Regulates Energy Balance via Alterations in Bile Acid Homeostasis

  Cellular and Molecular Gastroenterology and Hepatology · 2024-01-01 · 12 citations

  articleOpen access

  BACKGROUND & AIMS: Stearoyl-CoA desaturase-1 (SCD1) converts saturated fatty acids into monounsaturated fatty acids and plays an important regulatory role in lipid metabolism. Previous studies have demonstrated that mice deficient in SCD1 are protected from diet-induced obesity and hepatic steatosis due to altered lipid assimilation and increased energy expenditure. Previous studies in our lab have shown that intestinal SCD1 modulates intestinal and plasma lipids and alters cholesterol metabolism. Here, we investigated a novel role for intestinal SCD1 in the regulation of systemic energy balance. METHODS: To interrogate the role of intestinal SCD1 in modulating whole body metabolism, intestine-specific Scd1 knockout (iKO) mice were maintained on standard chow diet or challenged with a high-fat diet (HFD). Studies included analyses of bile acid content and composition, and metabolic phenotyping, including body composition, indirect calorimetry, glucose tolerance analyses, quantification of the composition of the gut microbiome, and assessment of bile acid signaling pathways. RESULTS: iKO mice displayed elevated plasma and hepatic bile acid content and decreased fecal bile acid excretion, associated with increased expression of the ileal bile acid uptake transporter, Asbt. In addition, the alpha and beta diversity of the gut microbiome was reduced in iKO mice, with several alterations in microbe species being associated with the observed increases in plasma bile acids. These increases in plasma bile acids were associated with increased expression of TGR5 targets, including Dio2 in brown adipose tissue and elevated plasma glucagon-like peptide-1 levels. Upon HFD challenge, iKO mice had reduced metabolic efficiency apparent through decreased weight gain despite higher food intake. Concomitantly, energy expenditure was increased, and glucose tolerance was improved in HFD-fed iKO mice. CONCLUSIONS: Our results indicate that deletion of intestinal SCD1 has significant impacts on bile acid homeostasis and whole-body energy balance, likely via activation of TGR5.

  PublisherOA PDFDOI

• Identification and Functional Characterization of Alternative Transcripts of LncRNA HNF1A-AS1 and Their Impacts on Cell Growth, Differentiation, Liver Diseases, and in Response to Drug Induction

  Non-Coding RNA · 2024-04-21 · 5 citations

  articleOpen access

  The long non-coding RNA (lncRNA) hepatocyte nuclear factor-1 alpha (HNF1A) antisense RNA 1 (HNF1A-AS1) is an important lncRNA for liver growth, development, cell differentiation, and drug metabolism. Like many lncRNAs, HNF1A-AS1 has multiple annotated alternative transcripts in the human genome. Several fundamental biological questions are still not solved: (1) How many transcripts really exist in biological samples, such as liver samples and liver cell lines? (2) What are the expression patterns of different alternative HNF1A-AS1 transcripts at different conditions, including during cell growth and development, after exposure to xenobiotics (such as drugs), and in disease conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD) cirrhosis, and obesity? (3) Does the siRNA used in previous studies knock down one or multiple transcripts? (4) Do different transcripts have the same or different functions for gene regulation? The presented data confirm the existence of several annotated HNF1A-AS1 transcripts in liver samples and cell lines, but also identify some new transcripts, which are not annotated in the Ensembl genome database. Expression patterns of the identified HNF1A-AS1 transcripts are highly correlated with the cell differentiation of matured hepatocyte-like cells from human embryonic stem cells (hESC), growth and differentiation of HepaRG cells, in response to rifampicin induction, and in various liver disease conditions. The expression levels of the HNF1A-AS1 transcripts are also highly correlated to the expression of cytochrome P450 enzymes, such as CYP3A4, during HepaRG growth, differentiation, and in response to rifampicin induction.

  PublisherOA PDFDOI

• Abstract ND06: First disclosure of AZD8421, a highly selective CDK2 inhibitor to address resistance to CDK4/6 inhibitors in breast and CCNE1-high cancers

  Cancer Research · 2024-04-05 · 9 citations

  article

  Abstract Cyclin-dependent kinases (CDKs) are an attractive class of cancer targets due to their role in cell-cycle regulation. CDK2 is a Ser/Thr kinase activated via interaction with its cyclin partners CCNE and CCNA, driving G1/S progression of the cell cycle. CDK2 inhibition has the potential to address multiple resistance mechanisms to CDK4/6 inhibitors in breast cancer. In addition, CCNE1 is frequently amplified and over-expressed in cancers including ovarian, with pre-clinical data linking CDK2 inhibition sensitivity to high CCNE1. First-generation inhibitors targeting CDK2 suffered from poor tolerability in the clinic likely due to off-target activities across both the CDK family and across the protein kinome. As well as achieving CDK family selectivity in cells versus key off-targets (CDK1, CDK4/6, CDK9), it’s noteworthy that AZD8421 had no significant kinase inhibition outside the CDK family. X-ray co-crystal structures of AZD8421 with CDK2 provided the basis for the observed selectivity among the CDK-family. For example, hydrogen bonding interaction of AZD8421 with Lys89 (a CDK2-specific residue) near the solvent region of the ATP-binding pocket was the key requisite for achieving >300-fold selectivity over CDK9. In nanoBRET assays measuring cellular target engagement, AZD8421 had an IC50 against CDK2 of 9nM with selectivity over CDK1, CDK4 and CDK6. Further kinetic characterization of AZD8421 binding revealed a long residence time at CDK2 (2 hours) but not CDK1 (7 minutes). These kinetic studies showed that AZD8421 has a low Kd,app for CDK2 and thus even higher selectivity vs CDK1 than was measured by single timepoint assays. In a CCNE1 amplified cell line, AZD8421 potently inhibited cell proliferation (69nM, OVCAR3), correlated with inhibition of pRB, arrest in G1/S phase of the cell cycle and induction of senescence. In vitro combination assays in CDK4/6 inhibitor resistant breast cancer cell lines showed combination benefit with AZD8421 plus approved CDK4/6 inhibitors. In vivo, AZD8421 potently suppressed phosphorylation of Rb, and demonstrated robust monotherapy and CDK4/6i combination activity in breast and ovarian in vivo models. In vivo PD marker suppression and efficacy was demonstrated in CDK4/6 inhibitor resistant breast PDXs in combination with palbociclib (CDK4/6i). AZD8421 showed robust monotherapy activity in a CCNE1 amplified ovarian model OVCAR3 with regressions seen with monotherapy and in combination with palbociclib. These data, along with suitable physical and pharmacokinetic properties, supported progression of AZD8421 into clinical studies [NCT06188520]. Citation Format: Christopher R. Denz, Michael Grondine, Jun Fan, Jessie Hao-Ru Hsu, Anne Jackson, James Robinson, Grace Guo, Wen Li, Yanjun Wang, Maryann San Martin, Laura Prickett, Jeffrey Johannes, Avipsa Ghosh, Kun Song, Dhivya Sudhan, Christina Vasalou, Ryan Richards, Kevin Beaumont, Matthew Peters, Lisa Drew, Stephen Fawell, Frederick W. Goldberg. First disclosure of AZD8421, a highly selective CDK2 inhibitor to address resistance to CDK4/6 inhibitors in breast and CCNE1-high cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr ND06.

  PublisherDOI

Recent grants

• Role of Intestinal Bile Acid Signaling in Liver Diseases

  NIH · 2017–2026

• NIH Grant R01DK081343

  NIH · $1.3M · 2013

• NIH Grant R56DK090036

  NIH · $328k · 2013

• NIH Grant P20RR021940

  NIH · $24.3M · 2016

• NIH Grant R21ES029258

  NIH · $426k · 2022

Frequent coauthors

• Bo Kong

  Guangdong Technion-Israel Institute of Technology

  238 shared

• Guodong Li

  Fourth Affiliated Hospital of Harbin Medical University

  99 shared

• Xiao‐bo Zhong

  University of Connecticut

  93 shared

• Daniel J. Rizzolo

  National University of Misiones

  88 shared

• Leonid Kagan

  Washington University in St. Louis

  84 shared

• Stephanie Piekos

  Boehringer Ingelheim (United States)

  83 shared

• Jie Lu

  83 shared

• Albert P. Li

  University of Florida

  82 shared

Education

• Ph.D., Toxicology

  University of ...

  2005

• Other, Medicine

  University of ...

  1998

Awards & honors

• Inaugural Presidential Outstanding Faculty Scholar Award at…
• James R. Gillette Drug Metabolism and Disposition Best Paper…
• Division for Toxicology Career Award, ASPET (2024)
• Fellow of AASLD (2020)