A5022045046- Gut microbiota and health
- Clostridium difficile and Clostridium perfringens research
- Colorectal Cancer Screening and Detection
- Oral microbiology and periodontitis research
- Bone Metabolism and Diseases
- Cancer Immunotherapy and Biomarkers
- Antibiotic Resistance in Bacteria
- Pancreatic and Hepatic Oncology Research
- Diet and metabolism studies
- Immune cells in cancer
- Oral health in cancer treatment
- Reproductive System and Pregnancy
- Viral gastroenteritis research and epidemiology
- CAR-T cell therapy research
- Evolution and Genetic Dynamics
- Salivary Gland Disorders and Functions
- Clinical Nutrition and Gastroenterology
- Streptococcal Infections and Treatments
- HIV/AIDS drug development and treatment
- Colorectal Cancer Surgical Treatments
- Pediatric Pain Management Techniques
- Adolescent and Pediatric Healthcare
- Childhood Cancer Survivors' Quality of Life
- Lipid metabolism and disorders
- Circadian rhythm and melatonin
The University of Texas Southwestern Medical Center
2019-2025
Southwestern Medical Center
2019-2024
Medical University of South Carolina
2017-2023
Center for Systems Biology
2021
Gut microbiota, specifically gut bacteria, are critical for effective immune checkpoint blockade therapy (ICT) cancer. The mechanisms by which microbiota augment extraintestinal anticancer responses, however, largely unknown. Here, we find that ICT induces the translocation of specific endogenous bacteria into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, lymph node remodeling dendritic cell (DC) activation, facilitates a selective subset to tissues promote...
Abstract Despite knowledge the gut microbiota regulates bone mass, mechanisms governing normal microbiota’s osteoimmunomodulatory effects on skeletal remodeling and homeostasis are unclear in healthy adult skeleton. Young specific-pathogen-free germ-free mice were used to delineate commensal immunoregulatory osteoblastogenesis, osteoclastogenesis, marrow T-cell hematopoiesis, extra-skeletal endocrine organ function. We report has anti-anabolic suppressing osteoblastogenesis pro-catabolic...
Abstract The antibiotic trimethoprim (TMP) is used to treat a variety of Escherichia coli infections, but its efficacy limited by the rapid emergence TMP-resistant bacteria. Previous laboratory evolution experiments have identified resistance-conferring mutations in gene encoding TMP target, bacterial dihydrofolate reductase (DHFR), particular mutation L28R. Here, we show that 4’-desmethyltrimethoprim (4’-DTMP) inhibits both DHFR and L28R variant, selects against bacteria carry experiments....
Commensal gut microbiota–host immune responses are experimentally delineated via gnotobiotic animal models or alternatively by antibiotic perturbation of microbiota. Osteoimmunology investigations in germ-free mice, revealing that microbiota immunomodulatory actions critically regulate physiologic skeletal development, highlight may dysregulate normal osteoimmunological processes. We investigated the impact disruption on osteoimmune response effects postpubertal development. Sex-matched...
Precision probiotics have shown great promise as novel therapies but not been fully realized. One major obstacle is that different strains of the same gut microbiota species can induce markedly variable phenotypic outcomes. Here, we aimed to optimize and validate in a preclinical model, six-species precision probiotic therapy for graft-versus-host disease (GVHD), an autoimmune complication following allogeneic stem cell transplantation. We had identified these six associated with protection...
The commensal gut microbiota critically regulates immunomodulatory processes that influence normal skeletal growth and maturation. However, the of specific microbes on osteoimmunoregulatory actions is unknown. We have shown previously enhances TH17/IL17A immune response effects in marrow liver procatabolic/antianabolic skeleton. Segmented filamentous bacteria (SFB), a bacterium within phylum Firmicutes, potently induces TH17/IL17A-mediated immunity. study purpose was to delineate SFB...
Commensal microbes critically regulate skeletal homeostasis, yet the impact of specific microbiota communities on osteoimmune response mechanisms is unknown. To discern osteoimmunomodulatory effects imparted by commensal oral that are distinct from systemic microbiota, osteoimmunology studies were performed in both alveolar bone and nonoral sites pathogen-free (SPF) versus germ-free (GF) mice SPF subjected to saline chlorhexidine rinses. GF had reduced cortical/trabecular an enhanced...
Disparities in incidence and outcome of rectal cancer are multifactorial etiology but may be due, part, to differences gut microbiome composition. We used serial robust statistical approaches assess baseline composition a diverse cohort patients with receiving definitive treatment.
Abstract Gut microbiota are critical for effective immune checkpoint blockade therapy (ICT) cancer. However, the underlying mechanisms by which gut and/or microbiota-derived metabolites augment antitumor response largely unknown. Here, we utilized a preclinical melanoma (B16-F10) model and treated groups of mice (Jackson, C57BL/6J, female, 6-8 wks, n=14-26 per group) with seven distinct antibiotic treatments to induce unique microbiomes metabolomes. Mice were then ICT (anti-PD-1...
Abstract Immune checkpoint inhibitor therapy (ICT) has revolutionized cancer care, but up to 50% of patients do not respond ICT. A host factor implicated in variable ICT response is the gut microbiome: a) germfree/antibiotic-treated mice ICT; b) human responders have distinct microbiome signatures compared non-responders; and c) fecal microbiota transplants are safe potentially effective previously unresponsive We established that induces translocation into secondary lymphoid tissues...
Abstract Immune checkpoint inhibitor therapy (ICT) can provide durable remissions for cancer patients with previously incurable malignancies. However, ICT is ineffective many types, and even those who initially respond may develop resistance succumb to their cancer. Tumor cell extrinsic factors, termed host have recently emerged as key mediators biomarkers of response. One intriguing factor that influence response the circadian clock, an evolutionarily conserved transcriptional-translational...
Microbes colonize anatomical sites in health to form commensal microbial communities (e.g., gut microbiota, skin oral microbiota). Commensal microbiota has indirect effects on host growth and maturation through interactions with the immune system. The was recently introduced as a novel regulator of skeletal morphology at noncraniofacial sites. Further, we others have shown that microbes, such segmented filamentous bacteria (SFB), contribute maturation. However, craniofacial are unclear. To...
Abstract Gut microbiota are critical for effective immune checkpoint blockade therapy (ICT) cancer. The mechanisms by which gut augment extraintestinal anti-cancer responses, however, largely unknown. Here, we find that ICT induces translocation of specific endogenous into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, activated dendritic cells (DCs) traffic a selective subset bacteria to mesenteric lymph nodes (MLN) promote optimal anti-tumor T-cell responses...
Abstract Introduction: Recent studies have identified bacteria associated with colorectal cancer (CRC), some data supporting causality in preclinical CRC models. We examined the gut microbiome composition and tumor genomic profiles a diverse cohort of rectal patients. Methods: Twenty-two patients newly-diagnosed, Stage II-IV without pathogenic germline mutations (mismatch repair genes, MUTYH) were included study. Gut profiling was performed on DNA extracted from collected fecal samples (16S...
Abstract Background In vitro studies have shown that enteric viruses require the gut microbiota (specific members of Enterobacteriaceae family) for efficient infection gastrointestinal tract. Human norovirus (NV) in transplant recipients may be chronic and severe. The role has not been defined this setting. We hypothesized diversity composition are different norovirus-infected patients. Methods performed a single-center, pilot, prospective cohort study adult solid-organ hematopoietic stem...