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Clifford Bogue, MD

Waldemar Von Zedtwitz Professor of Pediatrics; Chair, Pediatrics; Chief Medical Officer, Yale-New Haven Children's Hospital

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Clifford Bogue, MD

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Research Summary

The major focus of my research is to understand the molecular control of organ formation and cell-type specification. In particular, we are focusing on the role that homeobox genes play in early organogenesis, specifically the Hhex gene. Based on a null mutation of Hhex generated in my laboratory, we have determined that Hhex is crucial for early liver budding and morphogenesis, cardiovascular development, and lymphopoiesis. We plan to determine the precise role of Hhex in these critical developmental processes and the factors with which it interacts using mouse molecular genetics, conditional gene knockouts, and transgenic overexpression in specific cells and tissues. The two major areas of focus in the lab are the roles that Hhex plays in liver and cardiovascular development. By studying the specific role of Hhex during development, we will gain important insight into the basic developmental mechanisms involved in early organogenesis of a number of different organs. Ultimately, we plan to use the knowledge obtained by our study of the basic mechanisms of organ development to repair and regenerate organs and tissues in humans.

Specialized Terms: Role of homeobox transcription factors in early liver and cardiovascular development; Stem cells in organ repair and regeneration

Extensive Research Description

The major focus of my research is to understand the molecular control of organ formation and cell-type specification. In particular, we are focusing on the role that homeobox genes play in early organogenesis, specifically the Hhex gene. Based on a null mutation of Hhex generated in my laboratory, we have determined that Hhex is crucial for early liver budding and morphogenesis, cardiovascular development, and lymphopoiesis. We plan to determine the precise role of Hhex in these critical developmental processes and the factors with which it interacts using mouse molecular genetics, conditional gene knockouts, and transgenic overexpression in specific cells and tissues. The two major areas of focus in the lab are the roles that Hhex plays in liver and cardiovascular development. By studying the specific role of Hhex during development, we will gain important insight into the basic developmental mechanisms involved in early organogenesis of a number of different organs. Ultimately, we plan to use the knowledge obtained by our study of the basic mechanisms of organ development to repair and regenerate organs and tissues in humans.

  • Hhex – a homeobox gene essential for liver development. In this project, we are using mice with a liver-specific deletion of Hhex, derived in my lab, to gain insight into liver cell differentiation and bile duct morphogenesis.
  • Mechanism of polycystic liver disease in Hhex mutant mice. In this project, we are studying the role that Hhex deletion in the embryonic liver leads to polycystic liver disease.
  • Hhex and cardiovascular development. Hhex is critically important for normal heart and blood vessel development. This project focuses on the molecular mechanisms by which embryonic cardiovascular development is dependent on normal Hhex levels.

Coauthors

Research Interests

Critical Care; Gastroenterology; Morphogenesis; Pediatrics; Organogenesis

Selected Publications

  • Race, Ethnicity, and Socioeconomic Status in Research on Child HealthCheng T, Goodman E, Cheng T, Bogue C, Chien A, Dean J, Kharbanda A, Peeples E, Scheindlin B. Race, Ethnicity, and Socioeconomic Status in Research on Child Health Pediatrics 2015, 135: e225-e237. PMID: 25548336, DOI: 10.1542/peds.2014-3109.
  • Declined Presentation Critical roles for the homeodomain transcription factor hhex in lymphoid commitment and self-renewal of hematpoietic and leukaemic stem cellsShields B, Jackson J, Nasa C, Metcalf D, Bogue C, Alexander W, McCormack M. Declined Presentation Critical roles for the homeodomain transcription factor hhex in lymphoid commitment and self-renewal of hematpoietic and leukaemic stem cells Experimental Hematology 2014, 42: s48. DOI: 10.1016/j.exphem.2014.07.181.
  • Infectious Disease-Associated Syndromes in the PICULazar I, Bogue C. Infectious Disease-Associated Syndromes in the PICU 2014, 567-575. DOI: 10.1007/978-1-4471-6416-6_36.
  • Promoting Education, Mentorship, and Support for Pediatric ResearchCabana M, Cheng T, Bauer A, Bogue C, Chien A, Dean J, Scheindlin B, Kelle A. Promoting Education, Mentorship, and Support for Pediatric Research Pediatrics 2014, 133: 943-949. PMID: 24777211, PMCID: PMC8194448, DOI: 10.1542/peds.2014-0448.
  • Embryology and Development of the Ductal PlateBogue C. Embryology and Development of the Ductal Plate 2010, 3-21. DOI: 10.1007/978-1-60327-524-8_1.
  • The Proline-Rich Homeodomain (PRH/HEX) Protein Is Down-Regulated in Liver during Infection with Lymphocytic Choriomeningitis VirusDjavani M, Topisirovic I, Zapata J, Sadowska M, Yang Y, Rodas J, Lukashevich I, Bogue C, Pauza C, Borden K, Salvato M. The Proline-Rich Homeodomain (PRH/HEX) Protein Is Down-Regulated in Liver during Infection with Lymphocytic Choriomeningitis Virus Journal Of Virology 2008, 82: 8954-8954. PMCID: PMC2519670, DOI: 10.1128/jvi.01304-08.
  • Conditional deletion of the homeobox gene Hhex in the mouse liver results in polycystic liver diseaseHunter M, Wilson C, Kaestner K, Bogue C. Conditional deletion of the homeobox gene Hhex in the mouse liver results in polycystic liver disease The FASEB Journal 2007, 21: lb4-lb4. DOI: 10.1096/fasebj.21.6.lb4.
  • Genetic Models of Respiratory Tract DevelopmentBogue C. Genetic Models of Respiratory Tract Development 2001, 20013058: 59-89. DOI: 10.1201/b14019-7.
  • Immunocytochemical Characterization of Murine Hex, a Homeobox-Containing ProteinGhosh B, Ganea G, Denson L, Iannucci R, Jacobs H, Bogue C. Immunocytochemical Characterization of Murine Hex, a Homeobox-Containing Protein Pediatric Research 2000, 48: 634-638. PMID: 11044484, DOI: 10.1203/00006450-200011000-00014.
  • Hex expression suggests a role in the development and function of organs derived from foregut endodermBogue C, Ganea G, Sturm E, Ianucci R, Jacobs H. Hex expression suggests a role in the development and function of organs derived from foregut endoderm Developmental Dynamics 2000, 219: 84-89. PMID: 10974674, DOI: 10.1002/1097-0177(2000)9999:9999<::aid-dvdy1028>3.0.co;2-5.
  • Divergent homeobox gene Hex regulates promoter of the Na+-dependent bile acid cotransporterDenson L, Karpen S, Bogue C, Jacobs H. Divergent homeobox gene Hex regulates promoter of the Na+-dependent bile acid cotransporter AJP Gastrointestinal And Liver Physiology 2000, 279: g347-g355. PMID: 10915644, DOI: 10.1152/ajpgi.2000.279.2.g347.
  • HNF3β and GATA-4 transactivate the liver-enriched homeobox gene, HexDenson L, McClure M, Bogue C, Karpen S, Jacobs H. HNF3β and GATA-4 transactivate the liver-enriched homeobox gene, Hex Gene 2000, 246: 311-320. PMID: 10767553, DOI: 10.1016/s0378-1119(00)00082-2.
  • Genomic structure, cDNA mapping, and chromosomal localization of the mouse homeobox gene, HexGhosh B, Jacobs H, Wiedemann L, Brown A, Bedford F, Nimmakayalu M, Ward D, Bogue C. Genomic structure, cDNA mapping, and chromosomal localization of the mouse homeobox gene, Hex Mammalian Genome 1999, 10: 1023-1025. PMID: 10501975, DOI: 10.1007/s003359901152.
  • Pain management and weaning from narcotics and sedativesGanea G, Bogue C. Pain management and weaning from narcotics and sedatives Current Opinion In Pediatrics 1999, 11: 207-212. PMID: 10349097, DOI: 10.1097/00008480-199906000-00006.
  • Multiple Factors Regulate the Promoter Region of the Liver-Enriched Orphan Homeobox Protein, HexDenson L, Ghosh B, McClure M, Bogue C, Karpen S, Jacobs H. Multiple Factors Regulate the Promoter Region of the Liver-Enriched Orphan Homeobox Protein, Hex Pediatric Research 1999, 45: 110-110. DOI: 10.1203/00006450-199904020-00654.
  • Fetal Lung mRNA Levels of Hox Genes Are Differentially Altered by Maternal Diabetes and Butyrate in RatsJacobs H, Bogue C, Pinter E, Wilson C, Warshaw J, Gross I. Fetal Lung mRNA Levels of Hox Genes Are Differentially Altered by Maternal Diabetes and Butyrate in Rats Pediatric Research 1998, 44: 99-104. PMID: 9667378, DOI: 10.1203/00006450-199807000-00016.
  • Use of high-frequency and nonconventional ventilation for respiratory failureDonnelly K, Bogue C. Use of high-frequency and nonconventional ventilation for respiratory failure Current Opinion In Pediatrics 1998, 10: 278-283. PMID: 9716890, DOI: 10.1097/00008480-199806000-00010.
  • Hex Expression During Development Suggests an Important Role in Both Gastrulation and Organogenesis • 251Bogue C, Ganea G, Sturm E, Zhao F, Jacobs H. Hex Expression During Development Suggests an Important Role in Both Gastrulation and Organogenesis • 251 Pediatric Research 1998, 43: 45-45. DOI: 10.1203/00006450-199804001-00272.
  • The Na+-dependent bile acid cotransporter (NTCP) is a putative target gene for the liver-enriched, orphan homeobox protein, Hex • 581Jacobs H, Denson T, Karpen S, Bogue C. The Na+-dependent bile acid cotransporter (NTCP) is a putative target gene for the liver-enriched, orphan homeobox protein, Hex • 581 Pediatric Research 1998, 43: 102-102. DOI: 10.1203/00006450-199804001-00602.
  • Butyrate decreases homeobox gene expression in fetal rat lung in culture.† 256Gross I, Bogue C, Dynia D, Wilson C, Jacobs H. Butyrate decreases homeobox gene expression in fetal rat lung in culture.† 256 Pediatric Research 1997, 41: 45-45. DOI: 10.1203/00006450-199704001-00276.
  • RETINOIC ACID ENHANCES SURFACTANT PROTEIN GENE EXPRESSION. • 329Bogue C, Jacobs H, Dynia D, Wilson C, Gross I. RETINOIC ACID ENHANCES SURFACTANT PROTEIN GENE EXPRESSION. • 329 Pediatric Research 1996, 39: 57-57. DOI: 10.1203/00006450-199604001-00349.
  • Fatal enterovirus type 71 infectionLANDRY M, FONSECA S, COHEN S, BOGUE C. Fatal enterovirus type 71 infection The Pediatric Infectious Disease Journal 1995, 14: 1095-1100. PMID: 8745025, DOI: 10.1097/00006454-199512000-00013.
  • New approaches to diagnosis and therapy in pediatric critical careBogue C, Lister G. New approaches to diagnosis and therapy in pediatric critical care Current Opinion In Pediatrics 1992, 4: 431-436. DOI: 10.1097/00008480-199206000-00007.
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