About

James Samuel, PhD, is a Regents Professor and the Wofford Cain Endowed Chair in Infectious Disease at Texas A&M University Naresh K. Vashisht College of Medicine. His research focuses on the molecular pathogenesis of Coxiella burnetii, the agent of Q fever, which is an obligate intracellular bacterial pathogen and a category B biothreat agent. His laboratory investigates how C. burnetii interacts with host cells, particularly its strategies to down-regulate innate immune responses, its sensitivity to oxidative stress, and its mechanisms for survival and virulence. Dr. Samuel's work includes studying the secretion systems of the pathogen, identifying virulence factors, and understanding the differences between isolates from acute and chronic Q fever cases. He is also involved in vaccine and diagnostic development efforts against Q fever, exploring immune responses and protective immunity, with the goal of creating effective vaccines. His contributions have advanced the understanding of host-pathogen interactions and the molecular mechanisms underlying C. burnetii pathogenicity.

Research topics

• Biology
• Microbiology
• Virology
• Immunology
• Medicine

Selected publications

• Subverting Host Defense from Within: Innate Immune Modulation by Coxiella burnetii

  Pathogens · 2026-04-20

  articleOpen access

  -containing vacuole or CCV) through the action of its Type IVB secretion system (T4BSS). This system translocates a large repertoire of effector proteins into the host cytoplasm after phagosome acidification. These effectors interfere with diverse signaling pathways to co-opt host processes, such as vesicle trafficking, ubiquitylation, gene expression and lipid metabolism, promoting pathogen survival without triggering robust proinflammatory signaling or host cell death pathways. This effector-triggered immune silencing is particularly unique given the central role of macrophages as innate immune sentinels. In this review, we examine Cb T4BSS effectors that have been characterized as central determinants of innate immunity modulation. We discuss innate immune sensing pathways potentially engaged during infection, including Toll-like receptors, NOD-like receptors, RIG-I-like receptors, inflammasomes, and interferon signaling pathways, and highlight evidence indicating that these pathways are actively suppressed. Emphasis is placed on effector-mediated regulation of NF-κB signaling, type I interferon responses, and inflammasome activation. Finally, we address unresolved questions related to effector-triggered immunity, redundancy in immune suppression, and discrepancies between in vitro and in vivo infection models.

  PublisherDOI

• CYP1B1-AS1 regulates CYP1B1 to promote Coxiella burnetii pathogenesis by inhibiting ROS and host cell death

  Nature Communications · 2025-08-13 · 5 citations

  articleOpen accessSenior author

  Coxiella burnetii (Cb), the causative agent of Q fever, replicates within host macrophages by modulating immune responses through poorly understood mechanisms. Long non-coding RNAs (lncRNAs) are crucial yet underexplored regulators of inflammation, particularly in Cb pathogenesis. Employing a comparative transcriptomic analysis of THP-1 macrophages infected with 16 different microbes, we dissect a core set of immune-responsive lncRNAs such as MAILR, LINC01215, PACER, and MROCKI-common to human anti-pathogen responses, and distinguish them from lncRNAs specifically altered at early (1 h) time points in individual infections. In particular, our approach identifies lncRNA CYP1B1-AS1 as specifically upregulated in a spatiotemporal manner along with CYP1B1 in cis during Cb infection. Promoter assays confirm their co-regulation via a shared bidirectional promoter, while aryl hydrocarbon receptor (AHR)-lucia luciferase and nuclear translocation assays demonstrate that Cb infection activates AHR, driving their transcription. Knockdown of CYP1B1-AS1 or CYP1B1 alone disrupts mitochondrial homeostasis, increases ROS and mitochondrial dysfunction, and exacerbates apoptosis during infection. These findings position the CYP1B1-AS1/CYP1B1 axis as a key regulator of mitochondrial homeostasis under AHR signaling, supporting an intracellular environment that benefits Cb replication. Our results highlight the critical roles of lncRNAs in immune regulation and provide a valuable resource for future lncRNA research.

  PublisherOA PDFDOI

• Microfluidic droplets with amended culture media cultivate a greater diversity of soil microorganisms

  Applied and Environmental Microbiology · 2025-02-12 · 9 citations

  articleOpen access

  ABSTRACT Uncultivated but abundant soil microorganisms have untapped potential for producing broad ranges of natural products, as well as for bioremediation. However, cultivating soil microorganisms while maintaining a broad microorganism diversity to enable phenotyping and functional analysis of as diverse individual isolates as possible remains challenging. In this study, we developed and tested the ability of several culture media formulations that contain defined soil metabolites or soil extracts to maintain microorganism diversity during culture. We also assessed their performance in microfluidic droplet cultivation where single-soil microorganism isolates were encapsulated and cultivated in picoliter-volume water-in-oil emulsion droplets to enable clonal growth needed for downstream functional analyses. Our results show that droplet cultivation with media supplemented by soil extract or soil metabolites enables the recovery of soil microorganisms with higher diversity (up to 1.5-fold higher richness) compared to bulk cultivation methods. Importantly, 1.7-fold more of less abundant (<1%) phyla and 11-fold more of unique genera were recovered, demonstrating the utility of this method for interrogating highly diverse soil microorganisms for broad ranges of applications. IMPORTANCE Although soil microorganisms hold a significant value in bioproduction and bioremediation, only a small fraction—less than 1%—can be cultured under specific media and cultivation conditions. This indicates that there are ample opportunities in harvesting the diverse environmental microorganisms if isolating and recovering these uncultured microorganisms are possible. This paper presents a new cultivation technique composed of isolating single-soil microorganism cell from an in situ soil microorganism community in microfluidic droplets and conducting in-droplet cultivation in media supplemented by soil extract or soil metabolites. This method enables the recovery of a broader diversity of the original microorganism community, laying the groundwork for a high-throughput phenotyping of these diverse microorganisms from their natural habitats.

  PublisherDOI

• A clinical and histopathological insight into focal reactive gingival overgrowths: A case series

  International Journal of Applied Dental Sciences · 2025-10-01

  articleOpen accessSenior author

  Focal reactive gingival overgrowths constitute a group of non-neoplastic proliferative lesions that arise from the gingiva in response to chronic irritation or local trauma. Despite their overlapping clinical presentation, these lesions demonstrate distinct histopathological features that are essential for accurate diagnosis and differentiation from neoplastic conditions. The present case series provides an overview of the clinical presentation and histopathological characteristics of focal reactive gingival overgrowths encountered in three patients. All lesions were associated with local irritants and poor oral hygiene. Each case was managed through surgical excision, followed by histopathological evaluation, which confirmed the reactive nature of the lesions. Postoperative healing was uneventful, and no recurrence was observed during the follow-up period. This series reinforces the importance of comprehensive diagnostic assessment integrating clinical, radiographic, and histopathological findings. Although these lesions share a common etiopathogenesis, variations in their microscopic architecture reflect differences in tissue response to chronic irritation. Accurate diagnosis, meticulous removal of local irritants, complete surgical excision, and periodic follow-up are essential to ensure long-term stability and prevent recurrence.

  PublisherOA PDFDOI

• Management of surgical biopsy site using Platelet-Rich Fibrin (PRF) membrane: A case series

  International Journal of Applied Dental Sciences · 2024-01-01

  articleOpen accessSenior author

  In 2000, platelet-rich fibrin (PRF), the second generation of autologous platelet concentrates gained popularity for various applications in the medical and the dental fields, owing to its potentiality of better wound healing, epithelisation and regenerative property.In this paper, we report 2 cases of oral lesions which were indicated for biopsy. An excisional biopsy was performed to confirm the provisional diagnosis. However, healing from this type of oral biopsy can take several weeks due to the amount of tissue removed to prevent potentially adverse events following exposure of the bone surface, the biopsy site was managed with the use of PRF membrane. The clinical findings, histologic features and surgical management of the above cases are presented.

  PublisherOA PDFDOI

• CYP1B1-AS1 regulates CYP1B1 to promote Coxiella burnetii pathogenesis by inhibiting ROS and host cell death.

  Research Square · 2024-12-11 · 2 citations

  preprintOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Molecular mechanisms of <i>Coxiella burnetii</i> formalin-fixed cellular vaccine reactogenicity

  Infection and Immunity · 2024-10-02 · 2 citations

  articleOpen accessSenior author

  ABSTRACT Local and systemic reactogenic responses to Q-VAX have prevented licensing of this vaccine outside of Australia. These reactogenic responses occur in previously sensitized individuals and have not been well defined at the cellular level, in part because many studies have been done in guinea pigs that have limited molecular tools. We previously characterized a mouse model of reactogenicity where local reaction sites showed an influx of CD8+ and IFNγ-expressing IL17a+ CD4+ T cells consistent with a Th1 delayed-type hypersensitivity. In this study, we determined, using depletion and adoptive transfer experiments, that both anti- Coxiella antibodies and CD4+ T cells were essential for localized reactions at the site of vaccination. Furthermore, IFNγ depletion showed significant histological changes at the local reaction sites demonstrating the essential nature of this cytokine to reactogenicity. In addition to the cells and cytokines required for this response, we determined that whole cell vaccine (WCV) material remained at the site of vaccination for at least 26 weeks post-injection. Transmission electron microscopy (TEM) of these sites demonstrated intact rod-shaped bacteria at 2 weeks post-injection and partially degraded bacteria within macrophages at 26 weeks post-injection. Finally, because small cell variants (SCVs) are an environmentally stable form, we determined that local reactions were more severe when the WCV material was prepared with higher levels of SCVs compared to typical WCV or with higher levels of large cell variant (LCV). These studies support the hypothesis that antigen persistence at the site of injection contributes to this reactogenicity and that anti- Coxiella antibodies, CD4+ T cells, and IFNγ each contribute to this process.

  PublisherOA PDFDOI

• Vaccine development: obligate intracellular bacteria new tools, old pathogens: the current state of vaccines against obligate intracellular bacteria

  Frontiers in Cellular and Infection Microbiology · 2024-03-19 · 10 citations

  articleOpen accessSenior authorCorresponding

  Obligate intracellular bacteria have remained those for which effective vaccines are unavailable, mostly because protection does not solely rely on an antibody response. Effective antibody-based vaccines, however, have been developed against extracellular bacteria pathogens or toxins. Additionally, obligate intracellular bacteria have evolved many mechanisms to subvert the immune response, making vaccine development complex. Much of what we know about protective immunity for these pathogens has been determined using infection-resolved cases and animal models that mimic disease. These studies have laid the groundwork for antigen discovery, which, combined with recent advances in vaccinology, should allow for the development of safe and efficacious vaccines. Successful vaccines against obligate intracellular bacteria should elicit potent T cell memory responses, in addition to humoral responses. Furthermore, they ought to be designed to specifically induce strong cytotoxic CD8+ T cell responses for protective immunity. This review will describe what we know about the potentially protective immune responses to this group of bacteria. Additionally, we will argue that the novel delivery platforms used during the Sars-CoV-2 pandemic should be excellent candidates to produce protective immunity once antigens are discovered. We will then look more specifically into the vaccine development for Rickettsiaceae , Coxiella burnetti , and Anaplasmataceae from infancy until today. We have not included Chlamydia trachomatis in this review because of the many vaccine related reviews that have been written in recent years.

  PublisherOA PDFDOI

• μREACT: A microfluidic system for rapid evaluation of trans-kingdom interactions

  Biosensors and Bioelectronics · 2024-10-05

  article
  PublisherDOI

• Molecular Mechanisms of <i>Coxiella burnetii</i> Formalin Fixed Cellular Vaccine Reactogenicity

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-08-21

  preprintOpen accessSenior authorCorresponding

  Abstract Local and systemic reactogenic responses to Q-VAX® have prevented licensing of this vaccine outside of Australia. These reactogenic responses occur in previously sensitize individuals and have not been well defined at the cellular level, in part because many studies have been done in guinea pigs that have limited molecular tools. We previously characterized a mouse model of reactogenicity where local reactions sites showed an influx of CD8+ and IFNγ-expressing IL17a+ CD4+ T cells consistent with a Th1 delayed-type hypersensitivity. In this study we determined using depletion and adoptive transfer experiments that both anti- Coxiella antibodies and CD4+ T cells were essential for localized reactions at the site of vaccination. Furthermore, IFNγ depletion showed significant histological changes at the local reaction sites demonstrating the essential nature of this cytokine to reactogenicity. In addition to the cells and cytokines required for this response, we determined WCV material remained at the site of vaccination for at least 26 weeks post-injection. Transmission electron microscopy of these sites demonstrated intact rod-shaped bacteria at 2 weeks post-injection and partially degraded bacteria within macrophages at 26 weeks post-injection. Finally, since SCVs are an environmentally stable form, we determined that local reactions were more severe when the WCV material was prepared with higher levels of SCVs compared to typical WCV or with higher levels of LCV. These studies support the hypothesis that antigen persistence at the site of injection contributes to this reactogenicity and that anti- Coxiella antibodies, CD4+ T cells, and IFNγ each contribute to this process.

  PublisherOA PDFDOI

Recent grants

• Identification and Role of Type IV Secretion Effector Proteins in Coxiella burnetii

  NIH · $3.4M · 2012–2026

• NIH Grant R03AI092153

  NIH · $139k · 2013

• NIH Grant R01AI037744

  NIH · $1.8M · 2009

• NIH Grant R01AI048829

  NIH · $1.1M · 2005

• NIH Grant R29AI037744

  NIH · $582k · 2001

Frequent coauthors

• Erin J. van Schaik

  Texas A&M University

  58 shared

• Robert A. Heinzen

  National Institute of Allergy and Infectious Diseases

  46 shared

• Chen Chen

  35 shared

• Paul A. Beare

  National Institute of Allergy and Infectious Diseases

  33 shared

• Harley W. Moon

  31 shared

• Stephen F. Porcella

  National Institute of Allergy and Infectious Diseases

  29 shared

• Philip L. Felgner

  University of California, Irvine

  29 shared

• Diane C. Cockrell

  National Institute of Allergy and Infectious Diseases

  28 shared

Labs

• Vashisht College of MedicinePI

Education

• Ph.D., Microbiology

  Washington State University

  1986

• M.S., Biology

  Washington State University

  1983

• B.A., Zoology and Chemistry

  Miami University

  1976

Awards & honors

• Wofford Cain Endowed Chair in Infectious Disease