James Versalovic, M.D., Ph.D.

Metagenomics and the Human Microbiome
The laboratory is deeply engaged in the development of new strategies to characterize the composition and dynamics of the human microbiome. Refinement of DNA sequencing and microarray-based approaches are being deployed to understand the nature of mucosal-associated microbial communities. The Texas Children’s Microbiome Center (directed by Dr. Versalovic) aims to translate new knowledge about the human microbiome in different areas of medicine, in collaboration with different clinical specialists and the Human Genome Sequencing Center. Currently, we are trying to characterize the intestinal microbiome and the nature of the core microbiome in healthy children. In parallel, we are also studying the changes in the metagenome that may be associated with disorders of mucosal inflammation and recurrent abdominal (visceral) pain. The tools for analysis include next-generation DNA sequencing, quantitative PCR and high density microarrays to study shifts in the the metagenome and human-associated microbial communities.

Neuro-Immunology, Pain, and Inflammation – Mammal and Microbes
Many patients suffer from chronic disorders of inflammation and chronic pain disorders. Our laboratory has chosen to study intestinal inflammation and abdominal pain as opportunities to gain deeper insights into how specific microbes and the microbiome affect the pathophysiology of chronic diseases. With respect to inflammation, mouse colitis models and patients with inflammatory bowel disease (IBD, Crohn’s disease) are being studied in order to examine how fluctuations in metagenomes and microbial transcriptomes may affect patterns of mucosal immunity and immune signaling pathways. Commensal bacteria (as shown in this laboratory) suppress TNF signaling and MAP kinases in mammalian myeloid cells. NF-κB signaling and apoptosis/cell proliferation also appear to be co-regulated by secreted factors derived from commensal bacteria. Identification of bacterial genes and soluble mediators may result in the isolation of novel new drug candidates such as anti-inflammatory and analgesic compounds.

Children with recurrent abdominal pain and irritable bowel syndrome are now being studied in collaboration with the pediatric gastroenterology team at Texas Children’s Hospital. Pain signaling pathways are ripe for exploration including the regulation of pain/analgesic receptors in the intestinal mucosa and signaling pathways in epithelial cells and the enteric nervous system.

Cancer Prevention, Nutrition and the Microbiome
New projects are being developed for exploration of changes in the mammalian microbiome and how the metagenome may help us develop new strategies important for cancer prevention and human nutrition. Already, vitamin biosynthesis and other nutrient pathways have been identified in selected commensal microbes that may have implications for human nutrition. Next steps include beginning to understand how changes in the metagenome may influence metabolism of fatty acids and antioxidants that could modulate cell proliferation, apoptosis, and susceptibility to inflammation and cancer. Relationships between intestinal inflammation, neoplasia, and nutrition can be explored comprehensively in the context of the microbiome and probiotics research.

Bacterial-Host Genetics – Systems Biology – Metabolic Modeling
The laboratory has used a model commensal model organism, Lactobacillus reuteri, in order to study how microbes regulate signaling pathways in mammalian cells (mouse and human). Gene expression profiling of commensal bacteria by custom microarrays and next generation sequencing has enabled the laboratory to study key genes and pathways in prokaryotes that may provide signals or mediators of microbial:host interactions. Targeted and random mutagenesis strategies are being refined to explore biological pathways in microbial genomes and the metagenome and how these microbial signaling networks may be related to the dynamics of mucosal immunity and neurobiology in mouse models and human patients. New probiotics may be engineered or selected for therapeutic applications.