James Versalovic, M.D., Ph.D.
Professor of Molecular and Human Genetics
Milton J. Finegold Professor, Department of Pathology & Immunology
Professor, Departments of Pediatrics; and Molecular Virology & Microbiology
Co-Director, Medical Scientist Training Program, Baylor College of Medicine
Vice Chair for Clinical and Molecular Pathology, Baylor College of Medicine
Department Head and Service Chief, Pathology, Texas Children's Hospital
Director, Texas Children's Microbiome Center, Texas Children's Hospital
B.A., University of Texas at Austin, 1985
M.D., Ph.D., Baylor College of Medicine, 1995
Postdoc, Digestive Diseases, Baylor College of Medicine, 1996
Resident, Clinical Pathology, Massachusetts General Hospital, 1998
Clinical Fellow, Pathology, Harvard Medical School, 1999
Postdoc, Comparative Medicine, Massachusetts Institute of Technology, 1999
Intestinal Microbiome, Mucosal Immunity, Gut Inflammation, and Cancer
The Versalovic laboratory seeks to understand the nature of the mammalian gut microbiome and how gut bacteria (and probiotics) impact mucosal immunity and intestinal inflammation. Primary clinical interests are inflammatory bowel disease and colorectal cancer. The body site of primary interest is the mammalian intestine (small and large) using mouse models, mouse and human cell lines, and human specimens. Our group links the study of bacterial genomes and metagenomes to the systems biology of the mammalian intestines.
We are actively exploring microbiome replacement and manipulation of the intestinal microbiome as models of fecal transplantation programs in humans. Our aim is to cure disease by fundamentally changing the function or composition of the intestinal microbiome to prevent or treat disease phenotypes such as IBD and cancer. We believe that this strategy represents the microbial cell and gene therapy of the future.
Gut Microbiome, Inflammation and Immunity
Many patients suffer from inflammatory bowel disease (IBD; intestinal inflammation) and cancer associated with inflammation. Our laboratory studies intestinal inflammation as an opportunity to gain deeper insights into how specific microbes and the microbiome affect intestinal immunity. With respect to inflammation, mouse colitis models and patients with IBD are studied in order to examine how gut bacteria (commensal microbes) affect patterns of mucosal immunity and immune signaling pathways. Commensal bacteria suppress TNF/cytokine signaling and MAP kinases in epithelial and myeloid cells. Genes and pathways in the microbiome (such as amino acid decarboxylation pathways) have been identified as candidate anti-inflammatory and immunoregulatory modules of the microbiome.
Identification of bacterial genes and soluble mediators from the gut microbiome may result in the isolation of novel new drug candidates such as anti-inflammatory compounds. Biogenic amines and novel genes have recently been identified, and these genes and compounds can suppress intestinal inflammation in mouse colitis models. New strategies to replace, modify or transplant microbiomes in mouse models and patients will provide opportunities to change medicine and treat patients with debilitating chronic intestinal diseases such as refractory IBD.
Gut Microbiome and Cancer
Patients with IBD or chronic intestinal inflammation are at increased risk for colorectal cancer, and our goal is to reduce cancer risk by altering the microbiome (its composition and function). New projects will explore mechanisms of immunoregulation, regulation of cell proliferation, and cancer prevention by the gut microbiome. Intestinal microbes convert amino acids into anti-inflammatory compounds that may suppress intestinal inflammation and cancer in the intestine (colorectal cancer).
Nutrient metabolism by the microbiome may offer clues regarding the connections between diet, the gut microbiome, inflammation and cancer. Microbial metabolites may modulate cell proliferation, apoptosis, and susceptibility to inflammation and cancer. Epithelial cell proliferation and differentiation appears to be regulated by factors derived from commensal bacteria. Relationships between nutrition, intestinal inflammation, cell proliferation, and neoplasia can be explored comprehensively in the context of the microbiome and probiotics research.
- Thomas CM, Hong T, van Pijkeren JP, Hemarajata P, Trinh DV, Hu W, Britton RA, Kalkum M, Versalovic J (2012). Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS One 7(2): e31951. PubMed PMID: 22384111
- Preidis GA, Saulnier DM, Blutt SE, Mistretta TA, Riehle KP, Major AM, Venable SF, Barrish JP, Finegold MJ, Petrosino JF, Guerrant RL, Conner ME, Versalovic J (2012). Host Response to Probiotics Determined by Nutritional Status of Rotavirus-infected Neonatal Mice. J. Pediatr. Gastroenterol. Nutr. 55(3): 299-307. PubMed PMID: 22343914
- Preidis GA, Saulnier DM, Blutt SE, Mistretta TA, Riehle KP, Major AM, Venable SF, Finegold MJ, Petrosino JF, Conner ME, Versalovic J (2012). Probiotics stimulate enterocyte migration and microbial diversity in the neonatal mouse intestine. FASEB J. 26(5): 1960-9. PubMed PMID: 22267340
- Human Microbiome Project Consortium (2012). A framework for human microbiome research. Nature 486(7402): 215-221. PubMed PMID: 22699610.
- Saulnier DM, Riehle K, Mistretta TA, Diaz MA, Mandal D, Raza S, Weidler EM, Qin X, Coarfa C, Milosavljevic A, Petrosino JF, Highlander S, Gibbs R, Lynch SV, Shulman RJ, Versalovic J (2011). Gastrointestinal Microbiome Signatures of Pediatric Patients With Irritable Bowel Syndrome. Gastroenterology 141(5): 1782-91. PubMed PMID: 21741921
- Saulnier DM, Santos F, Roos S, Mistretta TA, Spinler JK, Molenaar D, Teusink B, Versalovic J (2011). Exploring metabolic pathway reconstruction and genome-wide expression profiling in Lactobacillus reuteri to define functional probiotic features. PLoS One 6(4): e18783. PubMed PMID: 21559529
James Versalovic, M.D., Ph.D.
Department of Pathology
Texas Children's Hospital
Feigin Center, Suite 830
1102 Bates Ave.
Houston, TX 77030
Web Site: Versalovic Lab