About

Jose C. Flores, D.O., is a faculty member in the Department of Family Medicine at Rutgers New Jersey Medical School. He earned his Doctor of Osteopathic Medicine degree in 1988 from UMDNJ School of Osteopathic Medicine. The available information does not include further details about his research focus, background, or key contributions.

Research topics

• Biology
• Genetics
• Microbiology
• Computer Science
• Computational biology
• Cell biology
• Biochemistry
• Pathology
• Medicine
• Immunology

Selected publications

• Rab11b is necessary for mitochondrial integrity and function in gut epithelial cells

  Frontiers in Cell and Developmental Biology · 2025-04-03 · 2 citations

  articleOpen access

  Introduction: The RAB11 family of small GTPases are intracellular regulators of membrane and vesicular trafficking. We recently reported that RAB11A and RAB11B redundantly regulate spindle dynamics in dividing gut epithelial cells. However, in contrast to the well-studied RAB11A functions in transporting proteins and lipids through recycling endosomes, the distinct function of RAB11B is less clear. Methods and Results: Our proteomic analysis of RAB11A or RAB11B interactome suggested a potential RAB11B specific involvement in regulating mitochondrial functions. Transcriptomic analysis of Rab11b knockout mouse intestines revealed an enhanced mitochondrial protein targeting program with an altered mitochondrial functional integrity. Flow cytometry assessment of mitochondrial membrane potential and reactive oxygen species production revealed an impaired mitochondrial function in vivo. Electron microscopic analysis demonstrated a particularly severe mitochondrial membrane defect in Paneth cells. Conclusion: These genetic and functional data link RAB11B to mitochondrial structural and functional maintenance for the first time.

  PublisherDOI

• LGG Enhances Gut Barrier Function by Modulating Arginine Metabolism and Vitamin B₃Synthesis

  Physiology · 2025-05-01

  article

  Gut barrier dysfunction is a hallmark of inflammatory bowel disease (IBD), characterized by increased intestinal permeability, epithelial disruption, and chronic inflammation. Despite growing insights into the gut microbiota’s role, the mechanisms underlying probiotic-driven metabolic reprogramming of gut barrier function remain elusive. This study hypothesizes that Lacticaseibacillus rhamnosus GG (LGG), in synergy with dietary tryptophan, reprograms host metabolism to restore intestinal homeostasis and enhance barrier integrity. Using germ-free mice colonized with LGG and fed tryptophan-deficient or -sufficient diets, we employed untargeted metabolomics, transcriptomics, and a novel metabolome-transcriptome correlation analysis (METRCA). Functional validation was performed via in vitro assays, ex vivo organoids, and DSS-induced colitis mouse models. LGG robustly enhanced gut barrier function through two complementary mechanisms. First, LGG significantly upregulated argininosuccinate lyase (ASL), a critical enzyme in arginine biosynthesis, alleviating the accumulation of argininosuccinate (ASA)—a barrier-disrupting metabolite that perturbs tight junction proteins such as Ocln and Tjp1. These effects were evident in both experimental colitis and human IBD, where reduced ASL expression correlated with disease severity. Second, LGG stimulated the production of methylnicotinamide (MNA), a vitamin B 3 derivative that exhibited potent barrier-protective effects by enhancing epithelial tight junctions and promoting healing in DSS-induced colitis. METRCA analyses revealed strong correlations between LGG-regulated metabolites, including indole derivatives and MNA, and genes associated with arginine metabolism and epithelial barrier integrity. Notably, MNA reduced intestinal permeability and inflammatory cytokine production, positioning it as a key effector in LGG’s mechanism of action. These findings were further validated by in silico analyses of human IBD datasets, demonstrating that LGG and dietary tryptophan synergistically modulate arginine biosynthesis and reduce ASA levels, ultimately mitigating gut barrier dysfunction. This study highlights LGG’s dual capacity to enhance gut barrier function by leveraging dietary tryptophan to drive arginine metabolism and vitamin B3 synthesis. By targeting the metabolic disruptions underlying IBD, LGG emerges as a transformative precision probiotic. These exciting findings establish a framework for microbiome-based therapeutic strategies, emphasizing the potential of dietary and probiotic interventions to restore intestinal barrier integrity in IBD and related disorders. (NIH R01-AT010243, R01-DK102934, R01-DK119198 and NSF 1754783) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

  PublisherDOI

• Genetic pre-adaptations in Saccharomyces cerevisiae Andean chicha isolates facilitate industrial brewery application

  Food Microbiology · 2025-05-14 · 4 citations

  articleOpen access1st author

  Strains of Saccharomyces cerevisiae were isolated from a traditionally produced Andean maize-based chicha from Ecuador and characterised with respect to their potential use in industrial beer brewing. Whole-genome sequencing revealed that the strains were related to the ‘French Guiana’ and ‘Mexican Agave’ S. cerevisiae clades, though the available evidence indicates that they belong to a previously undescribed population, and are thus unrelated to traditional European brewing strains. Small-scale screening for wort fermentation revealed two strains with brewing potential. These outperformed commercial reference brewing strains and had fermentation profiles and alcohol yields similar to those of diastatic S. cerevisiae strains of the Mosaic/Beer 2 group. Indeed, both strains possessed functional copies of the STA1 gene responsible for extracellular glucoamylase activity seen in diastatic members of the Beer 2 group. Sequence identity suggested that the same STA1 gene is shared by the chicha and Beer 2 strains despite their genomic dissimilarity, suggesting the possibility of ancient admixture. Pilot-scale brewing trials confirmed the wort fermentation potential of the chicha strains. Beers were characterised by high concentrations of fruity esters and the clove-like compound 4-vinylguaiacol, both of which are typical features of wheat beers and related styles. Sensory trials further confirmed the potential of these strains for brewing, with beers comparing favourably to one produced with a commercial wheat-beer strain under the same conditions. Apart from 4-vinylguaiacol, which is considered an essential flavour compound in wheat beers, no off-flavours were detected in test beers. Results highlight the value of assessing industrial brewing potential of non-European strains associated with traditional cereal-based fermentations. • Saccharomyces cerevisiae yeasts present in traditional chicha fermentations • Strains form an apparent sister population to known S. American populations • Domestication signatures include osmotolerance and wort sugar utilisation • Selected strains outperformed a comercial ale strain during wort fermentation • Evidence for an Andean origin of the STA1 gene associated with diastatic yeasts

  PublisherDOI

• Pre-Adaptations in Saccharomyces Cerevisiae Andean Chicha Isolates Facilitate Industrial Brewery Application

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access1st authorCorresponding
  PublisherDOI

• Simplified acid extraction and quantification of histones in human tumor cells

  Methods in cell biology · 2024-11-18 · 2 citations

  article
  PublisherDOI

• Response of the coccolithophore Calcidiscus leptoporus to environmental change during the industrial era in the Subantarctic Southern Ocean.

  Journal of Nannoplankton Research · 2024-01-01

  articleSenior author
  PublisherDOI

• Lactobacillus rhamnosus GG Stimulates Dietary Tryptophan-Dependent Production of Barrier-Protecting Methylnicotinamide

  Cellular and Molecular Gastroenterology and Hepatology · 2024-01-01 · 13 citations

  articleOpen access

  BACKGROUND & AIMS: Lacticaseibacillus rhamnosus GG (LGG) is the world's most consumed probiotic but its mechanism of action on intestinal permeability and differentiation along with its interactions with an essential source of signaling metabolites, dietary tryptophan (trp), are unclear. METHODS: Untargeted metabolomic and transcriptomic analyses were performed in LGG monocolonized germ-free mice fed trp-free or -sufficient diets. LGG-derived metabolites were profiled in vitro under anaerobic and aerobic conditions. Multiomic correlations using a newly developed algorithm discovered novel metabolites tightly linked to tight junction and cell differentiation genes whose abundances were regulated by LGG and dietary trp. Barrier-modulation by these metabolites were functionally tested in Caco2 cells, mouse enteroids, and dextran sulfate sodium experimental colitis. The contribution of these metabolites to barrier protection is delineated at specific tight junction proteins and enterocyte-promoting factors with gain and loss of function approaches. RESULTS: absorption abolishes barrier recovery in vivo. CONCLUSIONS: Our study uncovers a novel LGG-regulated dietary trp-dependent production of MNA that protects the gut barrier against colitis.

  PublisherDOI

• Metabolomic and Transcriptomic Correlative Analyses in Germ-Free Mice Link Lacticaseibacillus rhamnosus GG-Associated Metabolites to Host Intestinal Fatty Acid Metabolism and β-Oxidation

  Laboratory Investigation · 2024-01-20 · 4 citations

  articleOpen access
  PublisherOA PDFDOI

• Metabolomic and transcriptomic correlative analyses in germ free mice link probiotic-associated metabolites to host intestinal fatty acid metabolism and b-oxidation

  Physiology · 2024-05-01 · 1 citations

  article

  While a transcriptomics-led examination of the effects of probiotics offers valuable insights into their influence on host gene regulation, the dynamic interactions between host metabolism and probiotics require an integrated analysis and multiomics approach to provide deeper insight into the underlying molecular mechanisms governing these associations. Here, we developed a high throughput bioinformatic tool ‘metabolome-transcriptome correlation analysis’ (METRCA, in press) that can determine whether a certain gene-metabolite association is up or downregulated and predict whether a metabolite’s or gene’s tissue location impacts its interaction with one another. To test this, we analyzed by LCMS and bulk-RNA sequencing then assessed linkages between serum as well as fecal metabolites and disease- or metabolism-associated genes in the ileum of gnotobiotic mice fed either a tryptophan (trp)-deficient or -suffcient diet then mono-associated with Lactobacillus rhamnosus GG (LGG) or administered PBS (control). We discovered significant associations, mainly in LGG mice fed trp, between metabolites and ileal genes involved in fatty acid metabolism (FAM) and oxidation (FAO). This association was specific and not observed in GF mice gavaged with PBS, monocolonized with R. gnavus, or fed trp- diets, and in SPF mice. Many fecal trp metabolites like indole-3-acetamide and serum trp metabolites like indole acetonitrile were significantly, positively correlated with important intestinal FAM genes Dgat1 and Mgat2. Likewise, numerous fecal metabolites like 5-hydroytrp and several serum trp metabolites like serotonin emerged as positively correlated metabolites with the rate-limiting FAO genes Acaa2 and Cpt2. Serum indoles were more strongly associated with both FAM and FAO genes than fecal indoles. Few fecal and serum metabolites were found negatively correlated with FAM and FAO genes. Since most are positive correlators, these findings suggest a testable hypothesis that LGG- and trp-dependent metabolites increase the intestinal metabolism of dietary lipids, providing a mechanism to previous findings that LGG supplementation in mice protected against diet-induced obesity and fatty liver disease. Analytical approaches like METRCA can thus be used to extract valuable information from metabolite and RNA-Seq datasets, generating novel hypotheses that may discover new interactions between microbe- or nutrient-associated metabolites and host metabolic or disease-related pathways. NIHR01-AT010243 (NG,RF), R01DK119198 (NG), NSF 1754783 (RF)). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

  PublisherDOI

• The arginine and nitric oxide metabolic pathway regulate the gut colonization and expansion of Ruminococcous gnavus

  Journal of Biological Chemistry · 2024-07-30 · 8 citations

  articleOpen access1st authorCorresponding

  Ruminococcus gnavus is a mucolytic commensal bacterium whose increased gut colonization has been associated with chronic inflammatory and metabolic diseases in humans. Whether R. gnavus metabolites can modulate host intestinal physiology remains largely understudied. We performed untargeted metabolomic and bulk RNA-seq analyses using R. gnavus monocolonization in germ-free mice. Based on transcriptome-metabolome correlations, we tested the impact of specific arginine metabolites on intestinal epithelial production of nitric oxide (NO) and examined the effect of NO on the growth of various strains of R. gnavus in vitro and in nitric oxide synthase 2 (Nos2)-deficient mice. R. gnavus produces specific arginine, tryptophan, and tyrosine metabolites, some of which are regulated by the environmental richness of sialic acid and mucin. R. gnavus colonization promotes expression of amino acid transporters and enzymes involved in metabolic flux of arginine and associated metabolites into NO. R. gnavus induced elevated levels of NOS2, while Nos2 ablation resulted in R. gnavus expansion in vivo. The growth of various R. gnavus strains can be inhibited by NO. Specific R. gnavus metabolites modulate intestinal epithelial cell NOS2 abundance and reduce epithelial barrier function at higher concentrations. Intestinal colonization and interaction with R. gnavus are partially regulated by an arginine-NO metabolic pathway, whereby a balanced control by the gut epithelium may restrain R. gnavus growth in healthy individuals. Disruption in this arginine metabolic regulation will contribute to the expansion and blooming of R. gnavus.

  PublisherOA PDFDOI

Frequent coauthors

• Nan Gao

  Chinese Academy of Medical Sciences & Peking Union Medical College

  25 shared

• Ronaldo P. Ferraris

  Rutgers, The State University of New Jersey

  15 shared

• Michael P. Verzi

  14 shared

• Edward M. Bonder

  Rutgers, The State University of New Jersey

  14 shared

• Xiaoyang Su

  Rutgers, The State University of New Jersey

  12 shared

• Panan Suntornsaratoon

  Mahidol University

  11 shared

• Lanjing Zhang

  Peking University

  10 shared

• Kurt Widhalm

  9 shared

Education

• Other

  UMDNJ School of Osteopathic Medicine

  1988