About

Eric Brooks is an Assistant Professor at the Department of Molecular Biomedical Sciences at NC State University. His contact email is erbrook4@ncsu.edu. The page indicates his role within the department but does not provide specific details about his research focus, background, or key contributions.

Research topics

• Biology
• Immunology
• Anatomy
• Virology
• Genetics
• Cell biology
• Neuroscience
• Medicine

Selected publications

• Genetically engineered ESC-derived embryos reveal Vinculin-dependent force responses required for mammalian neural tube closure

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-25

  articleOpen access

  Abstract Epithelial sheets build complex structures by converting mechanical forces into changes in cell and tissue organization. During neural tube closure, the neural plate dynamically remodels to produce a closed tube that provides the structural foundation for the developing brain and spinal cord. How cells maintain epithelial integrity despite the forces required for tissue morphogenesis during neural tube closure is not understood. We show that mechanical forces are upregulated during cranial neural tube closure in the mouse embryo and recruit the force-sensitive protein Vinculin to adherens junctions. Leveraging a genetically engineered embryonic stem cell-based pipeline to efficiently generate mutant embryos, we show that Vinculin mutants produce mechanical forces correctly but fail to maintain cell adhesion under tension, resulting in a failure of cranial neural fold elevation. Live imaging of cell behavior in the developing midbrain reveals that apical constriction, cell rearrangement, and cell division initiate correctly in Vinculin mutants, but their progression is impeded by disruption of adherens junctions at sites of increased tension. These results demonstrate that Vinculin is required to reinforce cell adhesion in response to increasing physiological forces during cranial neural tube closure, and that this activity is necessary to translate these forces into changes in tissue structure.

  PublisherDOI

• Abstract 3242: DNA methylation profiling of Epstein-Barr virus (EBV) in lymphoproliferative disease reveals diagnostic and therapeutic applications

  Cancer Research · 2025-04-21

  article

  Abstract Introduction: Epstein-Barr Virus (EBV) is an oncogenic herpesvirus linked to hematologic malignancies. EBV enters latency within host cells and can undergo lytic activation, resulting in release of infectious virions. Latent EBV mediates malignant transformation, while lytic EBV is a frequent complication in immune suppression settings like post-transplant lymphoproliferative disease (PTLD). Current clinical assays detect only the presence of EBV via qPCR, limiting their diagnostic use. DNA methylation on EBV genomes is essential for interconversion of lytic/latent states, making it a promising virology biomarker. Methods: We have developed a high-throughput multiplex PCR profiling assay (iPLEX) to assess quantitative EBV DNA methylation at n=35 CpG dinucleotide sites in liquid biopsies (plasma/serum). We applied this assay to a cohort of n=246 plasma samples collected at the OSU Wexner Medical Center via the Leukemia Tissue Bank Shared Resource. Our cohort consisted of viremic patients with EBV-associated lymphoma or non-malignant EBV activation, including n=118 organ transplant recipients. We complemented our analysis with single molecule readout of EBV plasma methylomes (n=27) using Nanopore sequencing of native DNA methylation. Results: Low EBV methylation distinguished lytic from latent EBV (sensitivity: 93.3%, specificity: 97.2%), outperforming clinical EBV qPCR. We revealed distinct EBV methylation in lymphoma subtypes, ranging from intermediate (Hodgkin lymphoma, polymorphic PTLD) to high (Burkitt-, NK/T-cell lymphoma, monomorphic PTLD). Assessment of EBV methylation in treatment follow-up (n=55) highlighted malleable EBV methylation was associated with improved survival under treatment (p=0.0005). We further identified unique EBV methylation dynamics under epigenetic therapies, including DNA methyltransferase (DNMT) inhibitor decitabine. DNA methylation in the EBV protein kinase gene BGLF4 was further associated with response to antiviral ganciclovir (GCV) use. Lastly, assessment of overall methylation patterns revealed four EBV methylation groups. Single molecule methylome analysis via Nanopore sequencing validated our data and identified distinct states of molecular epigenetic heterogeneity in EBV lymphoma and PTLDs. Methylation groups showed highly significant association with overall survival in multiple disease entities, including Hodgkin- and diffuse large B-cell lymphoma (DLBCL). Conclusion: Our data reveal the epigenetic EBV landscape in lymphoma and non-malignant viremic conditions. EBV methylation can identify lymphoma through a minimally invasive plasma test for earlier and more reliable diagnosis of EBV-driven malignancy. EBV methylation could guide informed treatment decisions, especially with regard to epigenetic- and antiviral drug use, and aid in personalized care in the future. Citation Format: Christoph Weigel, Haley L. Klimaszewski, Cara Noel, Ada C. Sher, Kurtis M. Host, Yue-Zhong Wu, Sarah Y. Schlotter, Eric Brooks, Charles T. Gregory, Esko Kautto, Elshafa H. Ahmed, Rosemary Rochford, James S. Blachly, Mark Lustberg, Timothy Voorhees, Christopher C. Oakes, Robert A. Baiocchi. DNA methylation profiling of Epstein-Barr virus (EBV) in lymphoproliferative disease reveals diagnostic and therapeutic applications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3242.

  PublisherDOI

• Author response: A single-cell atlas of spatial and temporal gene expression in the mouse cranial neural plate

  2025-02-13

  peer-reviewOpen access1st authorCorresponding

  The formation of the mammalian brain requires regionalization and morphogenesis of the cranial neural plate, which transforms from an epithelial sheet into a closed tube that provides the structural foundation for neural patterning and circuit formation. Sonic hedgehog (SHH) signaling is important for cranial neural plate patterning and closure, but the transcriptional changes that give rise to the spatially regulated cell fates and behaviors that build the cranial neural tube have not been systematically analyzed. Here we used single-cell RNA sequencing to generate an atlas of gene expression at six consecutive stages of cranial neural tube closure in the mouse embryo. Ordering transcriptional profiles relative to the major axes of gene expression predicted spatially regulated expression of 870 genes along the anterior-posterior and mediolateral axes of the cranial neural plate and reproduced known expression patterns with over 85% accuracy. Single-cell RNA sequencing of embryos with activated SHH signaling revealed distinct SHH-regulated transcriptional programs in the developing forebrain, midbrain, and hindbrain, suggesting a complex interplay between anterior-posterior and mediolateral patterning systems. These results define a spatiotemporally resolved map of gene expression during cranial neural tube closure and provide a resource for investigating the transcriptional events that drive early mammalian brain development.

  PublisherDOI

• A single-cell atlas of spatial and temporal gene expression in the mouse cranial neural plate

  eLife · 2025-02-13

  preprintOpen access1st authorCorresponding

  Abstract The formation of the mammalian brain requires regionalization and morphogenesis of the cranial neural plate, which transforms from an epithelial sheet into a closed tube that provides the structural foundation for neural patterning and circuit formation. Sonic hedgehog (SHH) signaling is important for cranial neural plate patterning and closure, but the transcriptional changes that give rise to the spatially regulated cell fates and behaviors that build the cranial neural tube have not been systematically analyzed. Here we used single-cell RNA sequencing to generate an atlas of gene expression at six consecutive stages of cranial neural tube closure in the mouse embryo. Ordering transcriptional profiles relative to the major axes of gene expression predicted spatially regulated expression of 870 genes along the anterior-posterior and mediolateral axes of the cranial neural plate and reproduced known expression patterns with over 85% accuracy. Single-cell RNA sequencing of embryos with activated SHH signaling revealed distinct SHH-regulated transcriptional programs in the developing forebrain, midbrain, and hindbrain, suggesting a complex interplay between anterior-posterior and mediolateral patterning systems. These results define a spatiotemporally resolved map of gene expression during cranial neural tube closure and provide a resource for investigating the transcriptional events that drive early mammalian brain development.

  PublisherDOI

• Assessment of EBV DNA methlyation to guide antiviral use in EBV-associated lymphoma

  Blood · 2025-11-03

  articleOpen access

  Abstract Intro/Objective: Epstein-Barr Virus (EBV), an oncogenic herpesvirus, can drive human lymphoma development. EBV uses DNA methylation to silence its genome, switching from a lytic (active) to a latent (dormant) state, and it's widely understood that EBV remains latent in lymphoma. Current diagnostics provide no information on EBV activation state, though it could be useful for clinicians to pick appropriate antiviral (lytic) or lymphoma-directed (latent) therapy. The antiviral ganciclovir (GCV) is effective specifically against lytic EBV due to viral BGLF4 expression. Our group discovered BGLF4 expression in latent EBV+CNS lymphomas, which was associated with favorable outcomes to a GCV-containing treatment regimen (Dugan et al, Clin Ca Res, 2018). BGLF4 expression encoding potential for GCV response in other types of lymphomas remains unknown. We sought to first evaluate the landscape of BGLF4 methylation across EBV+lymphoma subtypes. We hypothesized that methylation loss at BGLF4 is associated with GCV response in EBV+lymphoma types, potentially serving as a high throughput and inexpensive cell-free DNA (cfDNA) biomarker to identify GCV candidates. Methods: We established a high-throughput PCR mass spectrometry assay quantifying methylation of n=12 CpG sites at the BGLF4 promoter (iPLEX). The assay was validated against the EpiTYPER methylation assay (r^2=0.766), methylation standards, and the limit of detection was determined. We assessed n=162 EBV+patient plasma samples from a cross-sectional study cohort including EBV-reactivations, post-transplant lymphoproliferation (PTLD), B-, T- and NK-cell lymphomas. Transcriptional activity, 5'RACE, and BGLF4 DNA methylation data were overlaid to determine methylation and expression association. Retrospective chart review was performed to determine GCV use and response association with BGLF4 methylation. Inclusion criteria for GCV response assessment was a negative 0.5log(10) change in viral load, lack of recent or current chemotherapy, rituximab, reduction in immunosuppression (RIS), and un-interrupted GCV use. Results: Our cohort consisted of n=23 NK/T cell lymphoma, n=15 Hodgkin lymphoma, n=39 PTLD, n=25 diffuse large B cell lymphoma (DLBCL), n=21 EBV viremia, and n=39 “other” samples, which were excluded from analysis. The average age was 55 years old (yo), median age was 59 yo (range: 20-86 yo). The iPLEX assay can be run on cfDNA from plasma in 10-12 hours. We identified DNA methylation loss at single CpG nucleotides correlated with BGLF4 expression (r2=0.73), demonstrating methylation can be used as a surrogate for gene expression. Unsupervised clustering of average methylation separated samples into 2 methylation patterns: group 1, of intermediate methylation, that contains a high methylation subgroup (subgroup 1a), and group 2, of low methylation. Cluster assignment was significantly associated with disease entity (p=0.0278), and post-hoc analysis showed that PTLDs were underrepresented in subgroup 1a (z=-2.89), and overrepresented in group 2 (z=2.49). NK/T cell lymphomas were underrepresented in group 2 (z=-2.20). We identified n=4 CpG sites within BLGF4 that were heterogeneously methylated among samples, deemed the BGLF4 core promoter. Strikingly, 42% of samples had ≤50% average core promoter methylation, demonstrating hypomethylation across disease groups. After applying inclusion criteria to assess GCV response, preliminary analysis showed that patients who responded to GCV (n=6) had a significantly lower BGLF4 methylation (p=0.0012) than patients who did not respond to GCV (n=7). N=5 GCV responders belong to group 2 designated by unsupervised clustering, and all GCV non-responders belong to group 1, presenting a methodology for stratifying out potential responders. These results suggest: (1) the novel finding that EBV exhibits site specific hypomethylation across multiple lymphoma types that correlates with BGLF4 gene expression; and (2) BGLF4 demethylation is clinically superior to viral load because it adds context to the epigenetic and histologic state, predicting antiviral sensitivity. Conclusions: We identified site specific BGLF4 methylation loss to be widespread in EBV+lymphoma, challenging the current dogma of EBV latency in lymphoma. Our BGLF4 demethylation assay is high throughput, inexpensive, and proves clinically superior to viral load alone, serving as a potential biomarker to successfully guide GCV administration in EBV-driven lymphomas.

  PublisherOA PDFDOI

• PRMT5 inhibition reduces hyperinflammation in a murine model of secondary hemophagocytic lymphohistiocytosis

  Blood Advances · 2025-01-18 · 1 citations

  articleOpen access

  ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) is a rare but aggressive and potentially lethal hyperinflammatory syndrome characterized by pathologic immune activation and excessive production of proinflammatory cytokines leading to tissue damage and multisystem organ failure. There is an urgent need for the discovery of novel targets and development of therapeutic strategies to treat this rare but deadly syndrome. Protein arginine methyltransferase 5 (PRMT5) mediates T-cell-based inflammatory responses, making it a potential actionable target for the treatment of HLH. Using CPG-1826 and anti-interleukin-10R (IL-10R) antibody, we induced murine secondary HLH in vivo with a marked expansion of splenic myeloid cell subsets and concurrent reduction of T- and natural killer (NK)-cell populations. PRMT5 expression was significantly upregulated in splenic T and NK lymphocytes, monocytes, and dendritic cells in mice with HLH (P < .05). Treatment with PRT382, a potent and selective PRMT5 inhibitor, significantly reduced physical signs of secondary HLH, including splenomegaly, hepatomegaly, and anemia (P < .0001 in each case), when compared with untreated mice. Inflammatory cytokines known to drive hyperinflammation in HLH, including interferon-γ and IL-6 were reduced to healthy levels with PRT382 treatment (P > .999 for both). PRT382 treatment also reduced the expansion of myeloid cell populations (P < .0001) in mice with HLH, compared with untreated mice, while restoring T- and NK-cell numbers (P < .001 for both). These results identify PRMT5 as a promising target for the management of secondary HLH and justify further exploration in this and other models of hyperinflammation.

  PublisherDOI

• Abstract A006: Assessment of EBV DNA methylation to guide antiviral use in EBV-associated lymphoma

  Cancer Immunology Research · 2025-09-24

  article

  Abstract Introduction/Objective: Epstein-Barr Virus (EBV) is an oncogenic herpesvirus driving development of human lymphomas. EBV uses DNA methylation to silence its genome and switch from a lytic (actively replicating) to a latent (dormant) state. Clinical treatment decisions for EBV-associated (EBV+) lymphomas are limited by current diagnostics which provide no information on EBV’s activation state, despite this playing an important role in lymphoma pathogenesis. The antiviral ganciclovir (GCV) is effective specifically against lytic EBV due to viral BGLF4 expression, a kinase that activates GCV. The Baiocchi group discovered that BGLF4 expression in otherwise latent EBV+CNS lymphomas was associated with favorable outcomes when patients received GCV-containing treatment regimen GARD. This indicated improved EBV+ lymphoma outcomes with GCV, yet we cannot determine which patients will benefit. We hypothesized that DNA methylation loss at BGLF4 indicates its expression and is associated with GCV response, serving as a potential DNA biomarker to determine which patients are suitable GCV candidates. Methods: We established a high-throughput PCR and mass spectrometry assay quantifying methylation of n=12 CpG sites at the BGLF4 promoter. The assay was validated against the EpiTYPER methylation assay (R^2=0.766), methylation standards, and the limit of detection was determined to be 625 copies/reaction. We assessed n=136 EBV+ patient plasma samples from a cross-sectional study cohort including EBV-reactivations, post-transplant lymphoproliferation (PTLD), B-, T- and NK-cell lymphomas. Methylation was analyzed with unsupervised clustering and overlaid with in vitro luciferase reporter data for respective BGLF4 DNA elements. Retrospective chart review was performed to determine GCV use and response association with BGLF4 methylation. Results: We identified n=4 CpG sites within BLGF4 that are heterogeneously methylated among samples and highlight the BGLF4 core promoter. Preliminary analysis showed that across disease groups, patients who responded to GCV had a significantly lower BGLF4 methylation (p=0.0007) than patients who did not respond to GCV. Comparatively, we saw no significant difference in BGLF4 methylation of rituximab responders versus non-responders (p=0.343). These results suggest BGLF4 demethylation may indicate lytic EBV activity and thus response to GCV. Conclusions/Significance: Site specific BGLF4 methylation loss is widespread in EBV+ lymphoma. Administration of GCV, a drug that has already been well studied and is FDA-approved, may be guided by EBV methylation, serving as a biomarker to improve patient outcomes in EBV-driven lymphomas. Citation Format: Cara M. Noel, Christoph Weigel, Haley LT. Klimaszewski, Ada C. Sher, Kurits M. Host, Yue-Zhong Wu, Sarah Y. Schlotter, Elshafa H. Ahmed, Eric Brooks, Christopher C. Oakes, James S. Blachly, Mark Lustberg, Timothy Voorhees, Robert A. Baiocchi. Assessment of EBV DNA methylation to guide antiviral use in EBV-associated lymphoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr A006.

  PublisherDOI

• GPR161–GLI3 repressor signaling at cilia directs apical constriction and cell fate during cranial neural tube closure

  Development · 2025-12-15 · 2 citations

  articleOpen access1st authorCorresponding

  Failure to close the cranial neural tube, known as exencephaly/anencephaly, is a lethal congenital defect. However, the mechanisms driving patterning and reshaping of the broad cranial neural folds are poorly understood. Loss of the primary cilium-localized G protein-coupled receptor GPR161 causes ectopic, excessive hedgehog signaling in the mouse neural tube and fully penetrant exencephaly. GPR161 promotes GLI3 transcriptional repressor (GLI3R) formation while preventing GLI2 transcriptional activator formation. Here, we studied the mechanisms underlying cranial closure in mice using a Gpr161 mutant allelic series, epistasis between Gpr161 knockout and GLI effectors, and in toto imaging of cell behavior. A functional non-ciliary Gpr161 knock-in implicated GPR161 ciliary localization directly in initiation and maintenance of cranial closure. Furthermore, Gli3R expression, but not Gli2 loss, rescued exencephaly in Gpr161 knockout mice. GLI3R specifically restricted forebrain ventral floor plate expansion and mediated apical constriction in the lateral midbrain neural folds prior to closure. These results reveal metamere-specific, cilia-dependent hedgehog repression thresholds in control of spatially restricted gene expression and dynamic cell behavior during cranial closure. Targeted interventions increasing hedgehog repression could ameliorate regional cranial defects.

  PublisherDOI

• Author response: A single-cell atlas of spatial and temporal gene expression in the mouse cranial neural plate

  2025-04-07

  peer-reviewOpen access1st authorCorresponding

  Single-cell RNA sequencing and computational analysis define a spatial and temporal map of gene expression during early patterning and morphogenesis of the mouse cranial neural plate, providing a resource for elucidating the transcriptional basis of mammalian brain development.

  PublisherDOI

• A single-cell atlas of spatial and temporal gene expression in the mouse cranial neural plate

  eLife · 2025-04-07 · 1 citations

  articleOpen access1st authorCorresponding

  The formation of the mammalian brain requires regionalization and morphogenesis of the cranial neural plate, which transforms from an epithelial sheet into a closed tube that provides the structural foundation for neural patterning and circuit formation. Sonic hedgehog (SHH) signaling is important for cranial neural plate patterning and closure, but the transcriptional changes that give rise to the spatially regulated cell fates and behaviors that build the cranial neural tube have not been systematically analyzed. Here, we used single-cell RNA sequencing to generate an atlas of gene expression at six consecutive stages of cranial neural tube closure in the mouse embryo. Ordering transcriptional profiles relative to the major axes of gene expression predicted spatially regulated expression of 870 genes along the anterior-posterior and mediolateral axes of the cranial neural plate and reproduced known expression patterns with over 85% accuracy. Single-cell RNA sequencing of embryos with activated SHH signaling revealed distinct SHH-regulated transcriptional programs in the developing forebrain, midbrain, and hindbrain, suggesting a complex interplay between anterior-posterior and mediolateral patterning systems. These results define a spatiotemporally resolved map of gene expression during cranial neural tube closure and provide a resource for investigating the transcriptional events that drive early mammalian brain development.

  PublisherDOI

Recent grants

• Control of cell behavior during cranial neural tube closure

  NIH · $178k · 2016–2019

Frequent coauthors

• Robert A. Baiocchi

  The Ohio State University

  19 shared

• John B. Wallingford

  The University of Texas at Austin

  17 shared

• Shelby Sloan

  The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

  16 shared

• Charlene Mao

  The Ohio State University

  15 shared

• Elshafa H. Ahmed

  The Ohio State University

  15 shared

• Sarah Schlotter

  The Ohio State University

  13 shared

• Polina Shindiapina

  The Ohio State University

  12 shared

• Frankie Jeney

  The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

  12 shared

Education

• PhD, Cell and Molecular Biology

  University of Texas at Austin

  2014