Jeffrey I. Gordon

Last updated

Jeffrey Ivan Gordon
Bornc. 1947 (age 75–76)
Nationality American
Alma mater University of Chicago
Oberlin College
Awards Copley Medal (2018)
Balzan Prize (2021)
Scientific career
Fields Medicine
Institutions Washington University in St. Louis

Jeffrey Ivan Gordon [1] (born c. 1947) is a biologist and the Dr. Robert J. Glaser Distinguished University Professor and Director of the Center for Genome Sciences and Systems Biology at Washington University in St. Louis. [2] He is internationally known for his research on gastrointestinal development and how gut microbial communities affect normal intestinal function, shape various aspects of human physiology including our nutritional status, and affect predisposition to diseases. [3] He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, the Institute of Medicine of the National Academies, and the American Philosophical Society. [4]

Contents

Education and early 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, 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 Dept. Molecular Biology & Pharmacology (1991–2004). Gordon is currently the Director of the Center for Genome Sciences (2004–present) at Washington University in St. Louis.

Gordon's early career focused on the development of cell lineages within the gastrointestinal tract. His laboratory initially combined the use of transgenic mouse models and biochemical approaches to elucidate the mechanisms of gut epithelial development along the duodenal-colonic and crypt-villus axes. Early studies also provided important insight into biochemical properties of lipid handling and transport in the digestive system. Dr. Gordon and colleagues later combined laser capture microdissection, and functional genomics to characterize specified cell populations within the gastrointestinal tract, including multipotent stem cells.

Gordon played a pivotal role in the study of protein N-myristoylation, a co-translational modification by which a myristoyl group is covalently attached to an N-terminal glycine residue of a nascent polypeptide. Gordon and his colleagues were instrumental in characterizing the mechanism by which N-myristoyltransferase (the enzyme that catalyzes the myristoylation reaction) selects its substrates and its catalytic mechanism. [5]

Gordon's group published a series of elegant studies that describe the ability of components of the commensal microbiota to induce specific responses in the host intestinal epithelium. One of these responses, the induction of intestinal cell surface fucose residues, is elicited by a prominent human intestinal symbiont, Bacteroides thetaiotaomicron, which can harvest and use the host fucose as a carbon and energy source. [6] Gordon's group published a seminal study in which functional genomics were used to document the genome-wide intestinal epithelial response to microbial colonization of the gastrointestinal tract. [7] Dr. Gordon's laboratory has investigated epithelial cell interaction with human-associated pathogens, including uropathogenic Escherichia coli , Helicobacter pylori , and Listeria monocytogenes .

Present research

Gordon and his laboratory are currently focused on understanding the mutualistic interactions that occur between humans and the 10–100 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. [8] 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. [9] 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. [10] 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. [11] [12] This approach has been extended to describe the role of the adaptive immune system in maintaining the host-microbial relationship. [13]

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. [14]

Selected honors

Related Research Articles

<span class="mw-page-title-main">Human microbiome</span> Microorganisms in or on human skin and biofluids

The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, biliary tract, and gastrointestinal tract. Types of human microbiota include bacteria, archaea, fungi, protists, and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.

<span class="mw-page-title-main">Bacillota</span> Phylum of bacteria

The Bacillota are a phylum of bacteria, most of which have gram-positive cell wall structure. The renaming of phyla such as Firmicutes in 2021 remains controversial among microbiologists, many of whom continue to use the earlier names of long standing in the literature.

<span class="mw-page-title-main">Gut microbiota</span> Community of microorganisms in the gut

Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut microbiota. The gut is the main location of the human microbiome. The gut microbiota has broad impacts, including effects on colonization, resistance to pathogens, maintaining the intestinal epithelium, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut–brain axis.

<span class="mw-page-title-main">Martin J. Blaser</span> American academic

Martin J. Blaser is the director of the Center for Advanced Biotechnology and Medicine at Rutgers (NJ) Biomedical and Health Sciences and the Henry Rutgers Chair of the Human Microbiome and Professor of Medicine and Pathology and Laboratory Medicine at the Rutgers Robert Wood Johnson Medical School in New Jersey.

<i>Bacteroides</i> Genus of bacteria

Bacteroides is a genus of Gram-negative, obligate anaerobic bacteria. Bacteroides species are non endospore-forming bacilli, and may be either motile or nonmotile, depending on the species. The DNA base composition is 40–48% GC. Unusual in bacterial organisms, Bacteroides membranes contain sphingolipids. They also contain meso-diaminopimelic acid in their peptidoglycan layer.

Intestinal permeability is a term describing the control of material passing from inside the gastrointestinal tract through the cells lining the gut wall, into the rest of the body. The intestine normally exhibits some permeability, which allows nutrients to pass through the gut, while also maintaining a barrier function to keep potentially harmful substances from leaving the intestine and migrating to the body more widely. In a healthy human intestine, small particles can migrate through tight junction claudin pore pathways, and particles up to 10–15 Å can transit through the paracellular space uptake route. There is some evidence abnormally increased intestinal permeability may play a role in some chronic diseases and inflammatory conditions. The most well understood condition with observed increased intestinal permeability is celiac disease.

Dysbiosis is characterized by a disruption to the microbiome resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, or a shift in their local distribution. For example, a part of the human microbiota such as the skin flora, gut flora, or vaginal flora, can become deranged, with normally dominating species underrepresented and normally outcompeted or contained species increasing to fill the void. Dysbiosis is most commonly reported as a condition in the gastrointestinal tract.

Microecology means microbial ecology or ecology of a microhabitat. In humans, gut microecology is the study of the microbial ecology of the human gut which includes gut microbiota composition, its metabolic activity, and the interactions between the microbiota, the host, and the environment. Research in human gut microecology is important because the microbiome can have profound effects on human health. The microbiome is known to influence the immune system, digestion, and metabolism, and is thought to play a role in a variety of diseases, including diabetes, obesity, inflammatory bowel disease, and cancer. Studying the microbiome can help us better understand these diseases and develop treatments.

<span class="mw-page-title-main">Claire M. Fraser</span> American genome scientist and microbiologist

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<span class="mw-page-title-main">Human Microbiome Project</span> Former research initiative

The Human Microbiome Project (HMP) was a United States National Institutes of Health (NIH) research initiative to improve understanding of the microbiota involved in human health and disease. Launched in 2007, the first phase (HMP1) focused on identifying and characterizing human microbiota. The second phase, known as the Integrative Human Microbiome Project (iHMP) launched in 2014 with the aim of generating resources to characterize the microbiome and elucidating the roles of microbes in health and disease states. The program received $170 million in funding by the NIH Common Fund from 2007 to 2016.

<span class="mw-page-title-main">Microbial symbiosis and immunity</span>

Long-term close-knit interactions between symbiotic microbes and their host can alter host immune system responses to other microorganisms, including pathogens, and are required to maintain proper homeostasis. The immune system is a host defense system consisting of anatomical physical barriers as well as physiological and cellular responses, which protect the host against harmful microorganisms while limiting host responses to harmless symbionts. Humans are home to 1013 to 1014 bacteria, roughly equivalent to the number of human cells, and while these bacteria can be pathogenic to their host most of them are mutually beneficial to both the host and bacteria.

<span class="mw-page-title-main">Microbiota</span> Community of microorganisms

Microbiota are the range of microorganisms that may be commensal, mutualistic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found to be crucial for immunologic, hormonal, and metabolic homeostasis of their host.

For the American folk-rock singer-songwriter, see Nancy Moran.

<span class="mw-page-title-main">Gut–brain axis</span> Biochemical signaling between the gastrointestinal tract and the central nervous system

The gut–brain axis is the two-way biochemical signaling that takes place between the gastrointestinal tract and the central nervous system (CNS). The "microbiota–gut–brain axis" includes the role of gut microbiota in the biochemical signaling events that take place between the GI tract and the CNS. Broadly defined, the gut–brain axis includes the central nervous system, neuroendocrine system, neuroimmune systems, the hypothalamic–pituitary–adrenal axis, sympathetic and parasympathetic arms of the autonomic nervous system, the enteric nervous system, vagus nerve, and the gut microbiota.

<span class="mw-page-title-main">Microbiome</span> Microbial community assemblage and activity

A microbiome is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps et al. as "a characteristic microbial community occupying a reasonably well-defined habitat which has distinct physio-chemical properties. The term thus not only refers to the microorganisms involved but also encompasses their theatre of activity". In 2020, an international panel of experts published the outcome of their discussions on the definition of the microbiome. They proposed a definition of the microbiome based on a revival of the "compact, clear, and comprehensive description of the term" as originally provided by Whipps et al., but supplemented with two explanatory paragraphs. The first explanatory paragraph pronounces the dynamic character of the microbiome, and the second explanatory paragraph clearly separates the term microbiota from the term microbiome.

<span class="mw-page-title-main">David Relman</span> American microbiologist

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<span class="mw-page-title-main">Pharmacomicrobiomics</span>

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Bile salt hydrolases (BSH) are microbial enzymes that deconjugate primary bile acids. They catalyze the first step of bile acid metabolism and maintain the bile acid pool for further modification by the microbiota. BSH enzymes play a role in a range of host and microbe functions including host physiology, immunity, and protection from pathogens.

References

  1. ↑ Akademien
  2. ↑ "Lab of Jeffrey I. Gordon • 2017 • Washington University in St. Louis". Archived from the original on August 7, 2019. Retrieved September 30, 2011.
  3. ↑ "Washington University News". Archived from the original on June 8, 2010. Retrieved February 19, 2008.
  4. ↑ "APS Member History". search.amphilsoc.org. Retrieved March 12, 2021.
  5. ↑ Kresge, Nicole; Simoni, Robert D.; Hill, Robert L. (2008). "N-Myristoyltransferase Substrate Selection and Catalysis: the Work of Jeffrey I. Gordon". Journal of Biological Chemistry. Elsevier BV. 283 (2): e2–e3. doi: 10.1016/s0021-9258(20)69031-7 . ISSN   0021-9258.
  6. ↑ Bry, L.; Falk, P. G.; Midtvedt, T.; Gordon, J. I. (September 6, 1996). "A Model of Host-Microbial Interactions in an Open Mammalian Ecosystem". Science. American Association for the Advancement of Science (AAAS). 273 (5280): 1380–1383. Bibcode:1996Sci...273.1380B. doi:10.1126/science.273.5280.1380. ISSN   0036-8075. PMID   8703071. S2CID   39804775.
  7. ↑ Hooper, L. V. (February 2, 2001). "Molecular Analysis of Commensal Host-Microbial Relationships in the Intestine". Science. American Association for the Advancement of Science (AAAS). 291 (5505): 881–884. Bibcode:2001Sci...291..881H. doi:10.1126/science.291.5505.881. ISSN   0036-8075. PMID   11157169.
  8. ↑ Bäckhed, Fredrik; Manchester, Jill K.; Semenkovich, Clay F.; Gordon, Jeffrey I. (January 8, 2007). "Mechanisms underlying the resistance to diet-induced obesity in germ-free mice". Proceedings of the National Academy of Sciences. 104 (3): 979–984. doi: 10.1073/pnas.0605374104 . ISSN   0027-8424. PMC   1764762 . PMID   17210919.
  9. ↑ Turnbaugh, Peter J.; Ley, Ruth E.; Mahowald, Michael A.; Magrini, Vincent; Mardis, Elaine R.; Gordon, Jeffrey I. (2006). "An obesity-associated gut microbiome with increased capacity for energy harvest". Nature. Springer Science and Business Media LLC. 444 (7122): 1027–1031. Bibcode:2006Natur.444.1027T. doi:10.1038/nature05414. ISSN   0028-0836. PMID   17183312. S2CID   4400297.
  10. ↑ Ley, Ruth E.; Turnbaugh, Peter J.; Klein, Samuel; Gordon, Jeffrey I. (2006). "Human gut microbes associated with obesity". Nature. Springer Science and Business Media LLC. 444 (7122): 1022–1023. doi:10.1038/4441022a. ISSN   0028-0836. PMID   17183309. S2CID   205034045.
  11. ↑ Sonnenburg, J. L. (March 25, 2005). "Glycan Foraging in Vivo by an Intestine-Adapted Bacterial Symbiont". Science. American Association for the Advancement of Science (AAAS). 307 (5717): 1955–1959. Bibcode:2005Sci...307.1955S. doi:10.1126/science.1109051. ISSN   0036-8075. PMID   15790854. S2CID   13588903.
  12. ↑ Samuel, B. S.; Hansen, E. E.; Manchester, J. K.; Coutinho, P. M.; Henrissat, B.; Fulton, R.; Latreille, P.; Kim, K.; Wilson, R. K.; Gordon, J. I. (June 11, 2007). "Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut". Proceedings of the National Academy of Sciences. 104 (25): 10643–10648. Bibcode:2007PNAS..10410643S. doi: 10.1073/pnas.0704189104 . ISSN   0027-8424. PMC   1890564 . PMID   17563350.
  13. ↑ Peterson, Daniel A.; McNulty, Nathan P.; Guruge, Janaki L.; Gordon, Jeffrey I. (2007). "IgA Response to Symbiotic Bacteria as a Mediator of Gut Homeostasis". Cell Host & Microbe. Elsevier BV. 2 (5): 328–339. doi: 10.1016/j.chom.2007.09.013 . ISSN   1931-3128. PMID   18005754.
  14. ↑ NIH Roadmap Archived December 10, 2010, at the Wayback Machine
  15. 1 2 "Gordon CV". Lab of Jeffrey I. Gordon. June 26, 2020. Retrieved February 23, 2021.
  16. ↑ "Jeffrey I. Gordon". www.balzan.org. Retrieved April 13, 2022.
  17. ↑ Princess of Asturias Awards 2023
  18. ↑ Albany Medical Center Prize 2023
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