Gastointestinal Hormone Research Core Center

Summary

Principal Investigator: Chung Owyang
Abstract: Recent advances in basic research techniques have led to an explosion of information and interest in the role of gastrointestinal peptides in health and disease. The function of these peptides has been shown to extend beyond their classical role as hormones to include actions as paracrine effectors, neurotransmitters, growth factors and cytokines. Peptides are well known to have a myriad of actions in the gastrointestinal tract, but also to have profound influences on the function of most of the body's organ systems. The ubiquitous distribution and myriad actions of gut peptides served as the catalyst that culminated in the formation of the University of Michigan Gastrointestinal Peptide Research Center;a successful multidisciplinary group of investigators that crosses traditional clinical disciplines and scientific boundaries. Advances in cell biology, biochemistry, and molecular biology have provided tools with which the genetic or molecular links between peptides and clinically relevant disorders of digestive function may be identified. The Center, through its Core laboratories and support of innovative Pilot/Feasibility projects, has provided expertise, technical and financial support that enables investigators to broaden the scope of their research. The 3 major thematic areas that reflect the common research Interests of numerous investigators affiliated with the Center remain unchanged. These include 1) Neurobiology in Appetite Control and Visceral Pain, 2) Molecular and Cellular Mechanisms of Inflammation, and 3) Cell Growth Differentiation and Program Cell Death. We have expanded our research in neurobiology in appetite control to include a new but related area which addresses peptide regulation of energy balance and metabolism. For research in inflammation, we plan to add a new Microbiome Core which is important to study host immunity and mucosal inflammation. The addition of Tom Wang and his program project on the use of confocal microendoscopy for early detection of Gl malignancy will enhance translational research in neoplastic cell growth. In response to advances in new technologies we have streamlined our core laboratories into 1.) molecular biology;2.) protein identification and localization core;3.) microbiome and inflammation and 4.) In vivo studies. Because most of the research involving cell imaging is to localize and characterize intracellular proteins, the Cell Biology Core is now combined with the Peptide and Proteomics Core. Proteins will be identified by mass spectrometry and their intracellular locations determined by immunohistochemistry and confocal fluorescence microscopy. The purpose of the new Microbiome Core is to provide Center investigators access to state of the art techniques for analysis of host/miorobiome interactions. The Peptide Center has galvanized the activities of a large number of researchers who investigate the actions of gut peptides at the University of Michigan, as well as attract new investigators to this field of research. Through the current application, we are seeking to continue and expand the Center with the hope that together the group will approach questions of fundamental importance in the pathophysiology, diagnosis, and treatment of Gl disorders in man.
Funding Period: 1996-12-01 - 2015-11-30
more information: NIH RePORT

Top Publications

  1. pmc Candida albicans and bacterial microbiota interactions in the cecum during recolonization following broad-spectrum antibiotic therapy
    Katie L Mason
    Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
    Infect Immun 80:3371-80. 2012
  2. pmc Glucose enhances leptin signaling through modulation of AMPK activity
    Haoran Su
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
    PLoS ONE 7:e31636. 2012
  3. pmc Significance of the microbiome in obstructive lung disease
    MeiLan K Han
    Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, 3916 Taubman Center, Box 5360, 1500 E Medical Center Drive, Ann Arbor, MI 48109 5360, USA
    Thorax 67:456-63. 2012
  4. pmc Hepatic TRAF2 regulates glucose metabolism through enhancing glucagon responses
    Zheng Chen
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA
    Diabetes 61:566-73. 2012
  5. pmc Herbal constituent sequoyitol improves hyperglycemia and glucose intolerance by targeting hepatocytes, adipocytes, and β-cells
    Hong Shen
    Dept of Molecular and Integrative Physiology, Univ of Michigan Medical School, Ann Arbor, MI 48109 0622, USA
    Am J Physiol Endocrinol Metab 302:E932-40. 2012
  6. pmc Ecological succession of bacterial communities during conventionalization of germ-free mice
    Merritt G Gillilland
    Division of Pulmonary and Critical Care Medicine, The University of Michigan Medical School, Ann Arbor, Michigan, USA
    Appl Environ Microbiol 78:2359-66. 2012
  7. pmc Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice
    Meredith A Collins
    Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA
    J Clin Invest 122:639-53. 2012
  8. pmc Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells
    Kelli L VanDussen
    Department of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor, MI 48109, USA
    Development 139:488-97. 2012
  9. pmc Genetic background of Prop1(df) mutants provides remarkable protection against hypothyroidism-induced hearing impairment
    Qing Fang
    Department of Human Genetics, University of Michigan, 4945 Buhl, 1241 E Catherine St, Ann Arbor, MI 48109 5618, USA
    J Assoc Res Otolaryngol 13:173-84. 2012
  10. pmc Keratin 8 phosphorylation regulates its transamidation and hepatocyte Mallory-Denk body formation
    Raymond Kwan
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0622, USA
    FASEB J 26:2318-26. 2012

Detail Information

Publications170 found, 100 shown here

  1. pmc Candida albicans and bacterial microbiota interactions in the cecum during recolonization following broad-spectrum antibiotic therapy
    Katie L Mason
    Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
    Infect Immun 80:3371-80. 2012
    ..Previous studies have focused on the ability of bacteria to alter C. albicans; this study addresses the ability of C. albicans to alter the bacterial microbiota during nonpathogenic colonization...
  2. pmc Glucose enhances leptin signaling through modulation of AMPK activity
    Haoran Su
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
    PLoS ONE 7:e31636. 2012
    ..These results suggest that glucose and/or its metabolites play a permissive role in leptin signaling, and that glucose enhances leptin sensitivity at least in part by attenuating the ability of AMPK to inhibit leptin signaling...
  3. pmc Significance of the microbiome in obstructive lung disease
    MeiLan K Han
    Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, 3916 Taubman Center, Box 5360, 1500 E Medical Center Drive, Ann Arbor, MI 48109 5360, USA
    Thorax 67:456-63. 2012
    ..Whether we can manipulate bacterial communities to improve clinical outcomes remains to be seen...
  4. pmc Hepatic TRAF2 regulates glucose metabolism through enhancing glucagon responses
    Zheng Chen
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA
    Diabetes 61:566-73. 2012
    ....
  5. pmc Herbal constituent sequoyitol improves hyperglycemia and glucose intolerance by targeting hepatocytes, adipocytes, and β-cells
    Hong Shen
    Dept of Molecular and Integrative Physiology, Univ of Michigan Medical School, Ann Arbor, MI 48109 0622, USA
    Am J Physiol Endocrinol Metab 302:E932-40. 2012
    ..Sequoyitol appears to directly target hepatocytes, adipocytes, and β-cells. Therefore, sequoyitol may serve as a new oral diabetes medication...
  6. pmc Ecological succession of bacterial communities during conventionalization of germ-free mice
    Merritt G Gillilland
    Division of Pulmonary and Critical Care Medicine, The University of Michigan Medical School, Ann Arbor, Michigan, USA
    Appl Environ Microbiol 78:2359-66. 2012
    ....
  7. pmc Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice
    Meredith A Collins
    Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA
    J Clin Invest 122:639-53. 2012
    ..They also strongly support the notion that inhibiting KrasG12D, or its downstream effectors, could provide a new approach for the treatment of pancreatic cancer...
  8. pmc Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells
    Kelli L VanDussen
    Department of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor, MI 48109, USA
    Development 139:488-97. 2012
    ..Our findings suggest that Notch targets distinct progenitor cell populations to maintain adult intestinal stem cells and to regulate cell fate choice to control epithelial cell homeostasis...
  9. pmc Genetic background of Prop1(df) mutants provides remarkable protection against hypothyroidism-induced hearing impairment
    Qing Fang
    Department of Human Genetics, University of Michigan, 4945 Buhl, 1241 E Catherine St, Ann Arbor, MI 48109 5618, USA
    J Assoc Res Otolaryngol 13:173-84. 2012
    ..Thus, the genetic background of Prop1(df) mutants is remarkably protective for most functions affected in other hypothyroid mice. The Prop1(df) mutant is an attractive model for identifying the genes that protect against deafness...
  10. pmc Keratin 8 phosphorylation regulates its transamidation and hepatocyte Mallory-Denk body formation
    Raymond Kwan
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0622, USA
    FASEB J 26:2318-26. 2012
    ..These findings may extend to neuropathies and myopathies that are characterized by intermediate filament-containing inclusions...
  11. pmc Decade-long bacterial community dynamics in cystic fibrosis airways
    Jiangchao Zhao
    Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 109:5809-14. 2012
    ..These features are the key parameters with which to assess the complex ecology of the CF airway...
  12. pmc c-Jun/AP-1 is required for CCK-induced pancreatic acinar cell dedifferentiation and DNA synthesis in vitro
    Lili Guo
    Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, Michigan 48109 5622, USA
    Am J Physiol Gastrointest Liver Physiol 302:G1381-96. 2012
    ..Monolayer culture can serve as a model to study acinar cell proliferation similar to regeneration after pancreatitis in vivo...
  13. pmc Conditional deletion of menin results in antral G cell hyperplasia and hypergastrinemia
    Natalia A Veniaminova
    Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, 48109 2200, USA
    Am J Physiol Gastrointest Liver Physiol 303:G752-64. 2012
    ..This result suggests that additional mutations in gene targets other than the Men1 locus are required to produce gastrin-secreting tumors...
  14. pmc Stabilization of the murine gut microbiome following weaning
    Patrick D Schloss
    Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA
    Gut Microbes 3:383-93. 2012
    ..These results suggest a high degree of stability in the microbiome once the community reached the second state...
  15. pmc The microbiome of the lung
    James M Beck
    Pulmonary Section, Medical Service, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, MI, USA
    Transl Res 160:258-66. 2012
    ..As this field advances over the next several years, we anticipate that studies using larger cohorts, multicenter designs, and longitudinal sampling will add to our knowledge and understanding of the lung microbiome...
  16. pmc Treating hepatitis C infection by targeting the host
    Shadi Salloum
    Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
    Transl Res 159:421-9. 2012
    ..In this review, we highlight some of the host factors that are particularly attractive targets for the treatment of HCV...
  17. pmc NF-κB–inducing kinase (NIK) promotes hyperglycemia and glucose intolerance in obesity by augmenting glucagon action
    Liang Sheng
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA
    Nat Med 18:943-9. 2012
    ..Therefore, overactivation of liver NIK in obesity promotes hyperglycemia and glucose intolerance by increasing the hyperglycemic response to glucagon and other factors that activate CREB...
  18. pmc IFNγ contributes to the development of gastric epithelial cell metaplasia in Huntingtin interacting protein 1 related (Hip1r)-deficient mice
    Zhiping Liu
    Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, 48109 2200, USA
    Lab Invest 92:1045-57. 2012
    ..Together, these findings demonstrate that IFNγ is critical for the development of the gastric epithelial cell metaplasia that results from parietal cell atrophy in the Hip1r-deficient mice...
  19. pmc How glycan metabolism shapes the human gut microbiota
    Nicole M Koropatkin
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Nat Rev Microbiol 10:323-35. 2012
    ....
  20. pmc Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy
    Sharon J Miller
    University of Michigan, Department of Internal Medicine, Division of Gastroenterology, 109 Zina Pitcher Pl BSRB 1522, Ann Arbor, Michigan 48109 2200, USA
    J Biomed Opt 17:021103. 2012
    ..Specific binding of two or more peptides can be distinguished in vivo using a novel multispectral endoscope to localize colonic dysplasia on real-time wide-field imaging...
  21. pmc The intestinal microbiota in health and disease
    Vincent B Young
    Division of Infectious Diseases, Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan, USA
    Curr Opin Gastroenterol 28:63-9. 2012
    ..This review discusses some of the recent work that reveals how the gut microbiome helps establish and protect intestinal health and how disturbances in this microbial community can lead to disease states...
  22. pmc Profiling CCK-mediated pancreatic growth: the dynamic genetic program and the role of STATs as potential regulators
    Grzegorz T Gurda
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0622, USA
    Physiol Genomics 44:14-24. 2012
    ....
  23. pmc Magnetization transfer helps detect intestinal fibrosis in an animal model of Crohn disease
    Jeremy Adler
    Department of Pediatrics, Division of Gastroenterology, University of Michigan Medical Center, 1150 W Medical Center Dr, A520B MSRB I, Box 5658, Ann Arbor, MI 48109, USA
    Radiology 259:127-35. 2011
    ..To determine the utility of magnetization transfer (MT) in the identification and quantification of intestinal fibrosis in a rat model of Crohn disease...
  24. pmc Absence of keratin 8 confers a paradoxical microflora-dependent resistance to apoptosis in the colon
    Aida Habtezion
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 108:1445-50. 2011
    ..Therefore, unlike the proapoptotic effect of K8 mutation or absence in hepatocytes, lack of K8 confers resistance to colonocyte apoptosis in a microflora-dependent manner...
  25. pmc Inhibition of gastric motility by hyperglycemia is mediated by nodose ganglia KATP channels
    Shi Yi Zhou
    Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, USA
    Am J Physiol Gastrointest Liver Physiol 300:G394-400. 2011
    ..These studies provide in vivo evidence that hyperglycemia induces gastric relaxation via the vagal afferent pathway. This action is mediated through inactivation of nodose ganglia K(ATP) channels...
  26. pmc A transient transgenic RNAi strategy for rapid characterization of gene function during embryonic development
    Bryan C Bjork
    Genetics Division, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 5:e14375. 2010
    ..Of the three methodologies tested, the PB transposon system produced high numbers of transgenic embryos with the expected phenotype, demonstrating its utility as a screening method...
  27. pmc Panhematin provides a therapeutic benefit in experimental pancreatitis
    Aida Habtezion
    University of Michigan Medical School, Department of Molecular and Integrative Physiology, Ann Arbor, Michigan, USA
    Gut 60:671-9. 2011
    ..In this study, we tested the utility of Panhematin, a water-soluble haemin formulation, in activating and inducing pancreatic HO-1, and as a therapeutic agent in treating mouse acute pancreatitis...
  28. pmc Lipocalin-13 regulates glucose metabolism by both insulin-dependent and insulin-independent mechanisms
    Kae Won Cho
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109 0622, USA
    Mol Cell Biol 31:450-7. 2011
    ..These data suggest that LCN13 regulates glucose metabolism by both insulin-dependent and insulin-independent mechanisms. LCN13 and LCN13-related molecules may be used to treat insulin resistance and type 2 diabetes...
  29. pmc Low-affinity CCK-A receptors are coexpressed with leptin receptors in rat nodose ganglia: implications for leptin as a regulator of short-term satiety
    Ying Li
    Univ of Michigan, 3912 Taubman Center, SPC 5362, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA
    Am J Physiol Gastrointest Liver Physiol 300:G217-27. 2011
    ..Many nodose neurons bearing low-affinity CCKAR express OB-Rb. These neurons also respond to mechanical distention. An interaction between CCKAR and OB-Rb in these neurons likely facilitates leptin mediation of short-term satiety...
  30. pmc Helicobacter pylori induction of the gastrin promoter through GC-rich DNA elements
    Tamara P Tucker
    Departments of Internal Medicine, Microbiology and Immunology and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109 2200, USA
    Helicobacter 15:438-48. 2010
    ..Since gastrin is an important regulator of gastric acid secretion and cell growth, H. pylori regulation of this hormone has been implicated in its pathogenesis...
  31. pmc In vivo fluorescence-based endoscopic detection of colon dysplasia in the mouse using a novel peptide probe
    Sharon J Miller
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
    PLoS ONE 6:e17384. 2011
    ..This finding highlights an innovative strategy for targeted detection to localize pre-malignant lesions that can be generalized to the epithelium of hollow organs...
  32. pmc Diabetic visceral hypersensitivity is associated with activation of mitogen-activated kinase in rat dorsal root ganglia
    Gintautas Grabauskas
    Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
    Diabetes 60:1743-51. 2011
    ..2 channels...
  33. pmc Hedgehog signaling controls homeostasis of adult intestinal smooth muscle
    William J Zacharias
    Department of Cell and Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA
    Dev Biol 355:152-62. 2011
    ....
  34. pmc Energy determinants GAPDH and NDPK act as genetic modifiers for hepatocyte inclusion formation
    Natasha T Snider
    Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
    J Cell Biol 195:217-29. 2011
    ..We propose that GAPDH and NDPK are genetic modifiers of murine DDC-induced liver injury and potentially human liver disease...
  35. pmc Interplay between the gastric bacterial microbiota and Candida albicans during postantibiotic recolonization and gastritis
    Katie L Mason
    Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
    Infect Immun 80:150-8. 2012
    ..albicans. Altogether, these data implicate a dichotomy between C. albicans colonization and gastric disease that is bacterial microbiome dependent...
  36. pmc PITX2 AND PITX1 regulate thyrotroph function and response to hypothyroidism
    F Castinetti
    Department of Human Genetics, University of Michigan, Ann Arbor, USA
    Mol Endocrinol 25:1950-60. 2011
    ..These results suggest that PITX2 and PITX1 have overlapping roles in thyrotroph function and response to hypothyroidism. The novel cre transgene that we report will be useful for studying the function of other genes in thyrotrophs...
  37. pmc Lipocalin 13 protein protects against hepatic steatosis by both inhibiting lipogenesis and stimulating fatty acid β-oxidation
    Liang Sheng
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 286:38128-35. 2011
    ..These results suggest that LCN13 decreases liver lipid levels by both inhibiting hepatic lipogenesis and stimulating β-oxidation. LCN13 deficiency is likely to contribute to fatty liver disease in obese mice...
  38. pmc Menin and JunD regulate gastrin gene expression through proximal DNA elements
    Edith J Mensah-Osman
    Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, 48109 2200, USA
    Am J Physiol Gastrointest Liver Physiol 301:G783-90. 2011
    ..In conclusion, proximal DNA elements within the human gastrin gene promoter mediate interactions between JunD, which induces gastrin gene expression and menin, which suppresses JunD-mediated activation...
  39. pmc Secretin is not necessary for exocrine pancreatic development and growth in mice
    Maria Dolors Sans
    Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, 48109 5622, USA
    Am J Physiol Gastrointest Liver Physiol 301:G791-8. 2011
    ..Camostat-fed littermate secretin and secretin receptor-deficient mice had similar pancreatic mass to WT mice. These results indicate that secretin is not required for normal pancreatic development or adaptive growth mediated by CCK...
  40. pmc Gastric tuft cells express DCLK1 and are expanded in hyperplasia
    Milena Saqui-Salces
    Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Pl BSRBI, Rm 2051, Ann Arbor, MI 48109 2200, USA
    Histochem Cell Biol 136:191-204. 2011
    ..g.,TRPM5. In summary, tuft cells appear in the gastric antrum and intestine at E18.5, but their maximal numbers in the corpus are not achieved until after weaning. Tuft cell numbers increase with inflammation, hyperplasia, and metaplasia...
  41. pmc Na+ channel Scn1b gene regulates dorsal root ganglion nociceptor excitability in vivo
    Luis F Lopez-Santiago
    Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109 0632, USA
    J Biol Chem 286:22913-23. 2011
    ..Consistent with this, transient outward K(+) current (I(to)) is significantly reduced in null DRG neurons. We conclude that Scn1b regulates the electrical excitability of nociceptive DRG neurons in vivo by modulating both I(Na) and I(K)...
  42. pmc Molecular characterization of the endoplasmic reticulum: insights from proteomic studies
    Xuequn Chen
    Department of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor, MI, USA
    Proteomics 10:4040-52. 2010
    ....
  43. pmc Butyrate-induced colonic hypersensitivity is mediated by mitogen-activated protein kinase activation in rat dorsal root ganglia
    Dabo Xu
    Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
    Gut 62:1466-74. 2013
    ....
  44. pmc Hepatoprotective role of Sestrin2 against chronic ER stress
    Hwan Woo Park
    Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA
    Nat Commun 5:4233. 2014
    ..The Sestrin2-mediated unfolded protein response (UPR) may be a general protective mechanism against ER stress-associated diseases. ..
  45. pmc Efficient, specific, developmentally appropriate cre-mediated recombination in anterior pituitary gonadotropes and thyrotropes
    Maria Ines Perez-Millan
    Department of Human Genetics, University of Michigan, Ann Arbor, Michigan
    Genesis 51:785-92. 2013
    ..This αGSU-iCre line is suitable for efficient, specific, and developmentally regulated deletion of floxed alleles in anterior pituitary gonadotropes and thyrotropes...
  46. pmc Intracellular lipid content is a key intrinsic determinant for hepatocyte viability and metabolic and inflammatory states in mice
    Liang Sheng
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan
    Am J Physiol Endocrinol Metab 305:E1115-23. 2013
    ..These data suggest that intracellular lipid content is a key intrinsic determinant for hepatocyte heterogeneity of metabolic, inflammatory, and survival states...
  47. pmc Genome-wide association of body fat distribution in African ancestry populations suggests new loci
    Ching Ti Liu
    Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America
    PLoS Genet 9:e1003681. 2013
    ..These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity...
  48. pmc Rab18 binds to hepatitis C virus NS5A and promotes interaction between sites of viral replication and lipid droplets
    Shadi Salloum
    Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
    PLoS Pathog 9:e1003513. 2013
    ..Our results support a model in which specific interactions between viral and cellular proteins may promote the physical interaction between membranous HCV replication foci and lipid droplets. ..
  49. pmc Dual oxidases control release of hydrogen peroxide by the gastric epithelium to prevent Helicobacter felis infection and inflammation in mice
    Helmut Grasberger
    Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan Electronic address
    Gastroenterology 145:1045-54. 2013
    ..The roles of DUOX in cellular interactions with microbes have not been determined in higher vertebrates...
  50. pmc Endothelial PAS domain protein 1 activates the inflammatory response in the intestinal epithelium to promote colitis in mice
    Xiang Xue
    Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan
    Gastroenterology 145:831-41. 2013
    ..HIF1α limits intestinal barrier dysfunction, but the role of EPAS1 has not been assessed under conditions of hypoxic inflammation or in models of IBD...
  51. pmc Modulation of post-antibiotic bacterial community reassembly and host response by Candida albicans
    John R Erb Downward
    Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, USA
    Sci Rep 3:2191. 2013
    ....
  52. pmc Drosophila Fip200 is an essential regulator of autophagy that attenuates both growth and aging
    Myungjin Kim
    Department of Molecular and Integrative Physiology University of Michigan Ann Arbor, MI USA
    Autophagy 9:1201-13. 2013
    ..These results suggest that Fip200 is a critical downstream component of Atg1 and specifically mediates Atg1's autophagy-, aging- and growth-regulating functions...
  53. pmc A conserved rod domain phosphotyrosine that is targeted by the phosphatase PTP1B promotes keratin 8 protein insolubility and filament organization
    Natasha T Snider
    From the Departments of Molecular and Integrative Physiology and
    J Biol Chem 288:31329-37. 2013
    ..Our results implicate the rod domain QYE motif tyrosine as an important determinant of IF assembly and solubility properties that can be dynamically modulated by phosphorylation. ..
  54. pmc Identification of a functional TPH1 polymorphism associated with irritable bowel syndrome bowel habit subtypes
    Helmut Grasberger
    Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA
    Am J Gastroenterol 108:1766-74. 2013
    ..In this study, we assessed the only common TPH1 proximal promoter variant (-347C/A; rs7130929) and its association with bowel habit predominance in IBS...
  55. pmc Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats
    Dabo Xu
    Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
    Gastroenterology 146:484-96.e4. 2014
    ..We propose that rifaximin modulates the ileal bacterial community, reduces subclinical inflammation of the intestinal mucosa, and improves gut barrier function to reduce visceral hypersensitivity...
  56. pmc Dynamics and associations of microbial community types across the human body
    Tao Ding
    Department of Microbiology and Immunology, 1500 W Medical Center, University of Michigan, Ann Arbor, Michigan 48109, USA
    Nature 509:357-60. 2014
    ..Understanding the diversity of community types and the mechanisms that result in an individual having a particular type or changing types, will allow us to use their community types to assess disease risk and to personalize therapies. ..
  57. pmc Quantifying size and number of adipocytes in adipose tissue
    Sebastian D Parlee
    Department of Molecular and Integrative Physiology, School of Medicine, University of Michigan, Ann Arbor, Michigan, USA
    Methods Enzymol 537:93-122. 2014
    ..In doing so, the method described herein is a useful tool for accurately quantifying WAT development, growth, and remodeling. ..
  58. pmc Mutation of caspase-digestion sites in keratin 18 interferes with filament reorganization, and predisposes to hepatocyte necrosis and loss of membrane integrity
    Sujith V W Weerasinghe
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Cell Sci 127:1464-75. 2014
    ..These findings might extend to other intermediate filament proteins that undergo proteolysis during apoptosis...
  59. pmc Leptin acts independently of food intake to modulate gut microbial composition in male mice
    Michael W Rajala
    Department of Internal Medicine, Division of Gastroenterology M W R, Division of Metabolism, Endocrinology and Diabetes C M P, M G M and Division of Infectious Disease J S O, S K F, V B Y Department of Microbiology and Immunology V B Y, Department of Molecular and Integrative Physiology M G M, and Neuroscience Program M G M, University of Michigan, Ann Arbor, Michigan
    Endocrinology 155:748-57. 2014
    ..Overall, our data reveal a role for LepRb signaling extrinsic to the intestinal epithelium and independent of food intake in the control of the gut microbiome. ..
  60. pmc Mathematical modeling of primary succession of murine intestinal microbiota
    Simeone Marino
    Department of Microbiology and Immunology and Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109
    Proc Natl Acad Sci U S A 111:439-44. 2014
    ..These results suggest future animal and in silico experiments. Our modeling approach can be applied to other systems to provide a greater understanding of the dynamics of communities associated with health and disease. ..
  61. pmc The microbiome and regulation of mucosal immunity
    Andrew J McDermott
    Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA
    Immunology 142:24-31. 2014
    ..Additionally, evidence continues to accumulate that alterations of the intestinal microbiome can impact not only gastrointestinal immunity but also immune regulation at distal mucosal sites. ..
  62. pmc The gut microbiome modulates colon tumorigenesis
    Joseph P Zackular
    Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
    MBio 4:e00692-13. 2013
    ....
  63. pmc Intestinal iron homeostasis and colon tumorigenesis
    Xiang Xue
    Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
    Nutrients 5:2333-51. 2013
    ..Limiting intratumoral iron through specifically chelating excess intestinal iron or modulating activities of iron transporter may be an attractive therapeutic target for CRC. ..
  64. pmc Changes in cystic fibrosis airway microbiota at pulmonary exacerbation
    Lisa A Carmody
    Department of Pediatrics and Communicable Disease, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Ann Am Thorac Soc 10:179-87. 2013
    ..In persons with cystic fibrosis (CF), repeated exacerbations of pulmonary symptoms are associated with a progressive decline in lung function. Changes in the airway microbiota around the time of exacerbations are not well understood...
  65. pmc Corticosterone mediates stress-related increased intestinal permeability in a region-specific manner
    G Zheng
    Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
    Neurogastroenterol Motil 25:e127-39. 2013
    ..It is unknown whether corticosterone (CORT) plays a role in mediating alterations of epithelial permeability in response to CPS...
  66. pmc Murine colitis is mediated by vimentin
    Nirit Mor-Vaknin
    Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI 48109 5640, USA
    Sci Rep 3:1045. 2013
    ..Our results suggest that vimentin impedes bacterial killing and production of ROS, thereby contributing to the pathogenesis of acute colitis...
  67. pmc NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer
    Aurélie Couturier-Maillard
    University Lille Nord de France, Lille, France
    J Clin Invest 123:700-11. 2013
    ....
  68. pmc Impact of intestinal PepT1 on the kinetics and dynamics of N-formyl-methionyl-leucyl-phenylalanine, a bacterially-produced chemotactic peptide
    Shu Pei Wu
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States
    Mol Pharm 10:677-84. 2013
    ..In conclusion, these findings demonstrated that PepT1 had a major influence on the permeability of fMet-Leu-Phe in duodenum, jejunum, and ileum in wild-type mice and on inflammatory response in intestinal regions that expressed PepT1...
  69. pmc Essential elements for glucosensing by gastric vagal afferents: immunocytochemistry and electrophysiology studies in the rat
    Gintautas Grabauskas
    Division of Gastroenterology, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, SPC 5362, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA
    Endocrinology 154:296-307. 2013
    ..Glucosensing requires a GLUT, GK, and K(ATP) channels. These elements are transported axonally to the gastric vagal afferents, which can be activated by elevated glucose through modulation of K(ATP) channels...
  70. pmc The microbiome in wound repair and tissue fibrosis
    Brittan S Scales
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
    J Pathol 229:323-31. 2013
    ....
  71. pmc Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3
    Jun Hee Lee
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, San Diego, CA 92093, USA
    Cell Metab 16:311-21. 2012
    ..These results demonstrate an important homeostatic function for the stress-inducible Sestrin protein family in the control of mammalian lipid and glucose metabolism...
  72. pmc Glucose and SIRT2 reciprocally mediate the regulation of keratin 8 by lysine acetylation
    Natasha T Snider
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Cell Biol 200:241-7. 2013
    ..Keratin acetylation provides a new mechanism to regulate keratin filaments, possibly via modulating keratin phosphorylation...
  73. pmc ZBP-89 regulates expression of tryptophan hydroxylase I and mucosal defense against Salmonella typhimurium in mice
    Bryan E Essien
    Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109 2200, USA
    Gastroenterology 144:1466-77, 1477.e1-9. 2013
    ..We investigated whether conditional deletion of ZBP-89 from the intestinal and colonic epithelium of mice increases their susceptibility to pathogens such as Salmonella typhimurium...
  74. pmc Lamin aggregation is an early sensor of porphyria-induced liver injury
    Amika Singla
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Cell Sci 126:3105-12. 2013
    ..The nuclear shape and lamin defects associated with porphyria phenocopy the changes seen in laminopathies and could result in transcriptional alterations due to sequestration of nuclear proteins...
  75. pmc Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform
    James J Kozich
    Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
    Appl Environ Microbiol 79:5112-20. 2013
    ..These analyses demonstrate that our approach can provide data that are at least as good as that generated by the 454 platform while providing considerably higher sequencing coverage for a fraction of the cost. ..
  76. pmc Rgg-associated SHP signaling peptides mediate cross-talk in Streptococci
    Betty Fleuchot
    INRA, UMR1319 MICALIS, Jouy en Josas, France AgroParisTech, UMR Micalis, Jouy en Josas, France
    PLoS ONE 8:e66042. 2013
    ..Interestingly, this does not seem to be dependent on the SHP/Rgg group and cross-talk between pathogenic and non-pathogenic streptococci is observed...
  77. pmc Cholecystokinin-mediated RhoGDI phosphorylation via PKCα promotes both RhoA and Rac1 signaling
    Maria Eugenia Sabbatini
    Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America
    PLoS ONE 8:e66029. 2013
    ..By mutational analysis we found that CCK-induced PKCα phosphorylation on RhoGDI1 at Ser96 releases RhoA and Rac1 from RhoGDI1 to facilitate Rho GTPases signaling...
  78. pmc Adenylyl cyclase 6 mediates the action of cyclic AMP-dependent secretagogues in mouse pancreatic exocrine cells via protein kinase A pathway activation
    Maria E Sabbatini
    Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
    J Physiol 591:3693-707. 2013
    ..In conclusion, several AC isoforms are expressed in pancreatic acini and ducts. AC6 mediates a significant part of pancreatic amylase and fluid secretion in response to secretin, VIP and forskolin through cAMP/PKA pathway activation...
  79. pmc Dominant protein interactions that influence the pathogenesis of conformational diseases
    Jordan Wright
    Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical Center, Ann Arbor, Michigan, USA
    J Clin Invest 123:3124-34. 2013
    ..These results offer new insight into dominant as well as recessive inheritance of conformational diseases and offer opportunities for the development of new therapies. ..
  80. pmc The emerging world of the fungal microbiome
    Gary B Huffnagle
    Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
    Trends Microbiol 21:334-41. 2013
    ..However, the impact of the mycobiome on human health is significant, especially as a reservoir for blooms of pathogenic microbes when the host is compromised and as a potential cofactor in inflammatory diseases and metabolic disorders. ..
  81. pmc Acute infection of mice with Clostridium difficile leads to eIF2α phosphorylation and pro-survival signalling as part of the mucosal inflammatory response
    Amir A Sadighi Akha
    Divisions of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109 5642, USA
    Immunology 140:111-22. 2013
    ..difficile and highlight eIF2α phosphorylation and the interleukin-22-pSTAT3-RegIIIγ axis as two of the pathways that could be used to contain and counteract the damage inflicted on the intestinal epithelium. ..
  82. pmc Dynamic responses of Bacteroides thetaiotaomicron during growth on glycan mixtures
    Theresa E Rogers
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Mol Microbiol 88:876-90. 2013
    ..Our results provide insight into how a bacterial glycan generalist modifies its responses in dynamic glycan environments and provide essential knowledge to interpret related metabolic behaviour in vivo...
  83. pmc The hypoxia-inducible factor-C/EBPα axis controls ethanol-mediated hepcidin repression
    Erik R Anderson
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA
    Mol Cell Biol 32:4068-77. 2012
    ..These data provide novel insight into the regulation of hepcidin by hypoxia and indicate that targeting HIFs in the liver could be therapeutic in ALD...
  84. ncbi CCK-induced pancreatic growth is not limited by mitogenic capacity in mice
    Stephen J Crozier
    Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Am J Physiol Gastrointest Liver Physiol 294:G1148-57. 2008
    ..These results indicate that CCK-stimulated growth of the pancreas is not limited by acinar cell mitogenic capacity but is due, at least in part, to inhibition of promitogenic Akt signaling...
  85. pmc New advances in acute pancreatitis
    Matthew J DiMagno
    University of Michigan Medical School, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ann Arbor, Michigan, USA
    Curr Opin Gastroenterol 23:494-501. 2007
    ..We focused on clinical aspects of acute pancreatitis, which contained new observations or insights into new or old concepts. For experimental acute pancreatitis we refer readers to a recent comprehensive review...
  86. pmc H pylori infection causes chronic pancreatitis in Mongolian gerbils
    Gabriele Rieder
    Max von Pettenkofer Institute, Pettenkoferstr 9a, D 80336 Munich, Germany
    World J Gastroenterol 13:3939-47. 2007
    ..To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type IV secretion system...
  87. ncbi Functional role of bone morphogenetic protein-4 in isolated canine parietal cells
    Hildegard Nitsche
    Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109 0682, USA
    Am J Physiol Gastrointest Liver Physiol 293:G607-14. 2007
    ..These findings may provide new clues for a better understanding of the mechanisms that regulate gastric epithelial cell growth and differentiation...
  88. ncbi Receptor-mediated regulation of tomosyn-syntaxin 1A interactions in bovine adrenal chromaffin cells
    Svetlana E Gladycheva
    Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 282:22887-99. 2007
    ..Thus, modulation of the tomosyn-syntaxin 1A interaction in response to secretagogue activation is an important mechanism allowing for dynamic regulation of the secretory response...
  89. ncbi Pioglitazone reverses insulin resistance and impaired CCK-stimulated pancreatic secretion in eNOS(-/-) mice: therapy for exocrine pancreatic disorders?
    Raju C Reddy
    Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, 1150 W Medical Center Drive, 6520 MSRB 1, Ann Arbor, MI 48109, USA
    Am J Physiol Gastrointest Liver Physiol 293:G112-20. 2007
    ..Insulin-sensitizing PPAR-gamma agonists such as pioglitazone may thus simultaneously correct endocrine and exocrine pancreatic disorders...
  90. pmc Hes1 is required for pituitary growth and melanotrope specification
    Lori T Raetzman
    University of Michigan, Ann Arbor 48109 0618, USA
    Dev Biol 304:455-66. 2007
    ..These results demonstrate that Notch signaling plays multiple roles in pituitary development, influencing precursor number, organ size, cell differentiation and ultimately cell fate...
  91. pmc Ankyrin repeat and SOCS box containing protein 4 (Asb-4) interacts with GPS1 (CSN1) and inhibits c-Jun NH2-terminal kinase activity
    Ji Yao Li
    Department of Surgery, University of Michigan, Ann Arbor 48109 0346, United States
    Cell Signal 19:1185-92. 2007
    ..The present study demonstrates that Asb-4 interacts with GPS1 and inhibits JNK activity...
  92. ncbi Intestinal epithelial cell proliferation is dependent on the site of massive small bowel resection
    Emir Q Haxhija
    Department of Pediatric Surgery, Medical University Graz, Graz, Austria
    Pediatr Surg Int 23:379-90. 2007
    ..However, the exact mechanisms, which guide these signalling pathways are still unclear...
  93. ncbi Genetic variation in C57BL/6 ES cell lines and genetic instability in the Bruce4 C57BL/6 ES cell line
    Elizabeth D Hughes
    Transgenic Animal Model Core, Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Mamm Genome 18:549-58. 2007
    ..Despite their tendency to aneuploidy and consequent inefficiency, use of Bruce4 ES cells can be valuable for models requiring behavioral studies and other mouse models that benefit from a defined C57BL/6 background...
  94. ncbi Reduced pepsin A processing of sonic hedgehog in parietal cells precedes gastric atrophy and transformation
    Yana Zavros
    Department of Internal Medicine Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 282:33265-74. 2007
    ..Moreover parietal cell atrophy, a known pre-neoplastic lesion, correlates with loss of Shh processing...
  95. pmc Nitric oxide pathways and evidence-based perturbations in acute pancreatitis
    Matthew J DiMagno
    Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
    Pancreatology 7:403-8. 2007
    ..The aims of this minireview are to describe normal intrapancreatic NO pathways, perturbations during experimental AP and due to epidemiological factors associated with pancreatic pathology, and the clinical implications of NO on AP...
  96. ncbi Hypoxia-inducible factor-1 target genes as indicators of tumor vessel response to vascular endothelial growth factor inhibition
    Duyen T Dang
    Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, MI 48109, USA
    Cancer Res 68:1872-80. 2008
    ..The data further show that DPP4 is a novel marker of HIF-1 induction. Altogether, these preclinical findings suggest novel clinical trials for predicting and monitoring tumor vessel responses to antiangiogenic therapy...
  97. ncbi Role for NMDA receptors in visceral nociceptive transmission in the anterior cingulate cortex of viscerally hypersensitive rats
    Xiaoyin Wu
    Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
    Am J Physiol Gastrointest Liver Physiol 294:G918-27. 2008
    ..The enhancement of excitatory glutamatergic transmission in the ACC appears to mediate this response. Furthermore, NMDA receptors mediate ACC synaptic responses after the induction of visceral hypersensitivity...
  98. ncbi Anterior cingulate cortex modulates visceral pain as measured by visceromotor responses in viscerally hypersensitive rats
    Zhijun Cao
    Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
    Gastroenterology 134:535-43. 2008
    ..We aimed to determine if ACC neuron activation enhances visceral pain in viscerally hypersensitive rats and to identify the receptor involved in facilitation of visceral pain...
  99. pmc A role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasion
    Longchuan Bai
    Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109 2200, USA
    FEBS Lett 581:5904-10. 2007
    ..Additionally, ectopic expression of CITED2 arrested RKO cell growth. Thus, CITED2 regulates colon cancer invasion and might be a target for HDAC inhibitor-based intervention of colon cancer...