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Jeffrey I. Gordon

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Jeffrey I. Gordon[1] (born October 4, 1947) is a biologist and the Dr. Robert J. Glaser Distinguished University Professor and Director of The Edison Family Center for Genome Sciences & Systems Biology at Washington University School of Medicine.[2] He is internationally known for his research on gastrointestinal development[3] and for founding the field of human microbiome research.[4] His research has revolutionized our understanding of the human microbiome and its roles in health and disease, particularly with regard to nutrition, digestion and metabolism.[5][6]

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Gordon’s research has significantly advanced scientific understanding of the human gut microbiome as a microbial “organ” that affects human health and disease beyond gastrointestinal health.[7] Much of his work has focused on addressing the global health challenge of childhood undernutrition.[8] Central questions that Gordon and his lab are pursuing include how our gut microbial communities influence human health, what interventions will repair microbial communities for an individual or a population to optimize healthy development, and how to create local infrastructures to deliver treatment in affordable, culturally acceptable, appetizing foods.[9] He and his team identified underdeveloped gut microbiota as a contributing cause of childhood malnutrition[10] and found that therapeutic food aimed at repairing the gut microbiome is superior to a widely used standard therapeutic food to treat childhood malnutrition.[11] Unlike standard therapeutic foods, these microbiome-directed foods improve long-term effects of malnutrition, including problems with metabolism, bone growth, immune function and brain development.[11]

Gordon has been elected to the National Academy of Sciences (2001),[12] the American Academy of Arts and Sciences (2004),[13] the National Academy of Medicine (2008),[14] and the American Philosophical Society (2014).[15]

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Education and career

Gordon received his bachelor's degree in Biology at 1969 at Oberlin College in Ohio. Over the next four years, Gordon received his medical training at the University of Chicago and graduated with honors in 1973. After two years as intern and junior assistant resident in Medicine at Barnes Hospital (now Barnes-Jewish Hospital), St. Louis, Gordon joined the Laboratory of Biochemistry at the National Cancer Institute as a Research Associate in 1975. He returned to Barnes Hospital in 1978 to become Senior Assistant Resident and then Chief Medical Resident at Washington University Medical Service. In 1981 he completed a fellowship in medicine (Gastroenterology) at Washington University School of Medicine. In the following years, Gordon rose quickly through the academic ranks at Washington University: Asst. Prof. (1981–1984); Assoc. Prof. (1985–1987); Prof. (1987–1991) of Medicine and Biological Chemistry. In 1991, he became head of the Department of Molecular Biology and Pharmacology (1991–2004). Gordon is currently the Director of The Edison Family Center for Genome Sciences & Systems Biology (2004–present) at Washington University in St. Louis.

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Early scientific research

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Gordon's early work focused on how the gastrointestinal epithelium is continuously renewed throughout life, and how its component cell types express different functions as they differentiate depending upon where they are located along the length of the gut.[16][17][18] This early work employed transgenic mice to study regulation of developmental-stage specific, cell type-specific and spatial patterns of gene expression using members of the fatty acid binding protein gene family as models.[19][20]

During this time he also  played a pivotal role in the study of protein N-myristoylation, a process by which the 14 carbon fatty acid, myristate, is covalently attached to an N-terminal glycine residue of proteins involved in cell signaling and other functions. Gordon’s group was instrumental in characterizing the substrate specificity of N-myristoyltransferase (Nmt), its catalytic mechanism and its atomic structure.[21] His genetic and biochemical studies provided evidence that Nmt is essential for the viability of fungi that are opportunistic pathogens and yielded enzyme inhibitors that functioned as anti-fungal agents.[22]

The Gordon lab’s transgenic and genetic mosaic mouse models provided evidence that spatial patterns of gene expression in gut epithelial cell lineages were dependent in part on cues from the environment.[23] In the early 1990s, he turned to the gut’s community of micro-organisms (microbiota) and their collective genes (microbiome) to search for these cues. In a simplified model of the human gut ecosystem that employed germ-free mice colonized with a single prominent human gut bacterial symbiont (Bacteroides thetaiotaomicron), his lab showed that this bacterium could direct a postnatal developmental program of expanding production of fucose-containing polysaccharides in the small intestinal epithelium but only if the organisms had functional genes for utilizing these host polysaccharides.[24][25] His follow-up functional genomics study of gnotobiotic mice colonized with just B. thetaioatomicron disclosed how a gut symbiont could influence many other aspects of gut biology.[26] By sequencing the B. thetaiotaomicron genome,[27] they found a repertoire of genes encoding enzymes that degrade polysaacharides; the number and type of these enzymes greatly exceeded those encoded in the human genome. This information enabled them to show in gnotobiotic mice how this organism can adaptively forage dietary and host glycans depending upon the diets they consumed.[28] B. thetaiotaomicron has subsequently become a leading model organism for dissecting the genetic and metabolic underpinnings of the symbiotic relationship between members of the gut microbiota and their human hosts – including how members sense/acquire/metabolize dietary polysaccharides.

These findings led his group to colonize germ-free animals with defined microbial communities of increasing complexity composed of cultured, genome-sequenced human gut microbiota members, so that questions about how members cooperate and compete in different nutrient environments to shape host physiology could be addressed. Encouraged by results obtained from these types of models, Gordon was lead author of an influential 2005 National Human Genome Research Institute white-paper entitled “Extending Our View of Self: the Human Gut Microbiome Initiative (HGMI)”.[29] In 2007, the Human Microbiome Project was listed on the NIH Roadmap for Medical Research as one of the New Pathways to Discovery.

Gordon’s efforts to link gut microbiome function to nutritional status initially focused on obesity and its associated metabolic dysfunction. This work involved characterization and subsequent transplantation of gut microbial communities from obese and lean mice, and later obese and lean twins including twin pairs discordant for obesity, into germ-free mice to characterize the effects of diet components on microbial community function and host physiology and metabolism.[30][31][32][33][34][35] These preclinical models and subsequent pilot clinical studies have been used to develop microbiome-targeted snack food prototypes composed of combinations of polysaccharides from sustainable sources that could improve microbiome function.[36][37][38]

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Present research

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Gordon and his laboratory are currently focused on understanding the mutualistic interactions that occur between humans and the 10 trillion commensal microbes that colonize each person's gastrointestinal tract. To tease apart the complex relationships that exist within this gut microbiota, Dr. Gordon's research program employs germ-free and gnotobiotic mice as model hosts, which may be colonized with defined, simplified microbial communities. These model intestinal microbiotas are more amenable to well-controlled experimentation.

Gordon has become an international pioneer in the study of gut microbial ecology and evolution, using innovative methods to interpret metagenomic and gut microbial genomic sequencing data. In recent studies, Dr. Gordon's lab has established that the gut microbiota plays a role in host fat storage and obesity.[39] Gordon and co-workers have used DNA pyrosequencing technology to perform metagenomics on the intestinal contents of obese mice, demonstrating that the gut microbiota of fat mice possess an enhanced capacity for aiding the host in harvesting energy from the diet.[40] A study of the microbial ecology of obese human subjects on two different weight loss diets indicate that the same principles may be operating in humans.[41] His group has applied the sequencing of bacterial and archaeal genomes to describe the microbial functional genomic and metabolomic underpinnings of microbial adaptation to the gastrointestinal habitat.[42][43] This approach has been extended to describe the role of the adaptive immune system in maintaining the host-microbial relationship.[44]

Gordon is the lead author of an influential 2005 National Human Genome Research Institute white-paper entitled “Extending Our View of Self: the Human Gut Microbiome Initiative (HGMI)”. In 2007 the Human Microbiome Project was listed on the NIH Roadmap for Medical Research as one of the New Pathways to Discovery.[45]

Selected honors

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Major awards and honors received by Gordon include:

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References

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