The Seed Research Group broadly studies the interactions of mammals and microbes to understand how microbial communities alter health and disease and how pathogenic microbes emerge from those communities to cause specific infections of the respiratory tract, urinary tract, blood, and central nervous system. The Seed Research Group combines human clinical studies, conventional and germ-free animal models, molecular genetics, immunology, biochemistry, structural biology, high-dimensional data computational analysis, and complementary 'omics technologies including genomics, metagenomics, transcriptomics, metatranscriptomics, and metabolomics to understand complex systems. We use the lessons learned from these molecular studies to design new diagnostics and therapeutics.
Patrick C. Seed, MD
THE ROLE OF CORYNEBACTERIUM SPECIES IN RESPIRATORY HEALTH
In this project, we dissect the pangenome of the genus Corynebacterium and use molecular biology, cellular assays , and animal models to identify the mechanisms through which Corynebacterium spp. compete with other respiratory bacteria and alter the host response to inflammation and infection. Bacterial pneumonia remains one of the leading global causes of death among young children. The respiratory microbiota is hypothesized as a mediator of respiratory health and exclusion of bacterial pneumonia pathogens.
We and others previously mapped the infant nasopharyngeal microbiota and identified an inverse relationship between the presence of Corynebacterium spp. and respiratory pathogens such as Streptococcus pneumoniae. However, Corynebacterium spp. remain poorly understood and their mechanisms of interacting with the host and other microbes is poorly described. In collaboration with Dr. Matthew Kelly, we have assembled a growing sample collection from the human nasopharynx and culture collection including diverse corynebacteria. Using a combination of genomics, metagenomics, transcriptomics, respiratory cell culture models, molecular genetics, biochemistry, and murine models, we are identifying the diverse mechanisms through which Corynebacterium spp. attach and engage host epithelial cells, augment immune and inflammatory responses, and directly and indirectly inhibit other respiratory organisms including pneumonia pathogens.
THE PEDIATRIC OBESITY MICROBIOME & METABOLISM STUDY (POMMS)
In collaboration with investigators at Duke University, we are investigating the childhood and adolescent gut microbiome and its relationship to pediatric overweight and obesity. We predicted that children with obesity have different microbiota and metabolic signatures than healthy weight children and adults with obesity.
We conducted a prospective, longitudinal study of over 300 youth, performing marker gene and shotgun metagenomics and metabolomic profiling. We are conducting integrative data modelling to determine the relationship between clinical measures, microbiome, and metabolic factors. We are conducting model system studies to identify causal relationships between microbial communities, metabolic states, and mechanistic pathways to corroborate the human associative studies. Together, we seek to understand how the earlier stages of obesity and metabolic plasticity are established prior to the development of fixed, late stage adult disease. Insights into the early disease stages may inform effective interventions to alter and reverse the obesity and associated metabolic disturbances.
FOOD ALLERGY OUTCOMES RELATED TO WHITE AND AFRICAN AMERICAN RACIAL DIFFERENCES (FORWARD)
In collaboration with Dr. Ruchi Gupta and the Center for Food Allergy and Asthma Research at Northwestern University, we are using shotgun metagenomics and high dimensional data analysis to identify differences in microbiome composition by racial identify among children with food allergies. With rich clinical, social, nutritional, and environmental data and serial fecal samples, the study will find correlates between food allergy type, severity, race, and clinical parameters.
Dr. Seed's lab aims to translate molecular knowledge of microbial/microbiome genetics, physiology, and pathogenesis into diagnostics and treatments for a broad range of pediatric diseases. The Seed Research Team combines human clinical studies, conventional and germ-free models, molecular genetics, immunology, biochemistry, structural biology, high-dimensional data computational analysis, and complementary 'omics technologies including genomics, metagenomics, transcriptomics, metatranscriptomics, and metabolomics to understand complex systems.