Overview
Our research program focuses on molecular regulation of digestive system development. The major areas of investigation are:
- Hlx homeobox transcription factor regulation of digestive system development
- Genetics of anorectal malformations in humans
- Gene expression in developing and maturing intestine
Hlx
Hlx is required for normal growth and development of the intestine and liver in mouse embryos. Our overall hypothesis is that the specific expression of the Hlx protein results in regulation of the development of the intestine and liver (including enteric neurons and intestinal mesenchyme) by directing the expression of genes encoding proteins participating in interactions of mesenchyme with other tissues. Current investigations focus on understanding the control of expression of Hlx itself, identifying genes that are regulated by Hlx (downstream targets), investigating development of enteric neurons and smooth muscle in Hlx knockout mice, and analyzing the expression of a number of interesting genes identified in microarray-based comparisons of gene expression in the presence and absence of Hlx.
Anorectal malformations
Dr. Bates is also pursuing a "translational developmental biology" project to identify genes required for normal human hindgut development. Alteration of this development results in anorectal malformations, in which the GI tract ends in a blind pouch or with a fistula to the skin or into the genitourinary tract. Evidence from humans and animals suggest an important genetic component to these birth defects. This study is being performed in association with the Colorectal Center of Cincinnati Children's.
Gene expression in developing intestine
Dr. Bates is also participating in a cross-divisional effort to examine gene expression profiles in a large number of mouse tissues using DNA microarrays, focusing on gene expression along the anterior-posterior (proximal-distal) axis of the GI tract and in development and maturation of the GI tract. This work was the subject of an article in Cincinnati Children's Research Horizons newsletter.
Publications
- Bates, Michael D.; Schatzman, Lynn C.; Harvey, Richard P.; and Potter, S. Steven (2001). Two CCAAT Boxes in a Novel Inverted Repeat Motif Are Required for Hlx Homeobox Gene Expression. Biochimica et Biophysica Acta 1519:96-105.
- Bates, Michael D. and Balistreri, William F. (2002). The Gastrointestinal Tract: Development of the Human Digestive System. In: Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant, Seventh Edition. (Ed. by A.A. Fanaroff and R.J. Martin) St. Louis: Mosby, pp. 1255-1263.
- Bates, Michael D. (2002). Development of the Enteric Nervous System. Clinics in Perinatology 29:97-114.
- Bates, Michael D.; Erwin, Christopher R.; Sanford, L. Philip; Wiginton, Dan; Bezerra, Jorge A.; Schatzman, Lynn C.; Jegga, Anil G.; Ley-Ebert, Cathy; Williams, Sarah S.; Steinbrecher, Kris A.; Warner, Brad W.; Cohen, Mitchell B.; and Aronow, Bruce J. (2002). Novel Genes and Functional Relationships in the Adult Mouse Gastrointestinal Tract Identified by Microarray Analysis. Gastroenterology 122:1467-1482.
- Bates, Michael D. and Balistreri, William F. (2002). Conjugated and Unconjugated Hyperbilirubinemia and Disorders of the Hepatobiliary Tree. In: Gellis and Kagan's Current Pediatric Therapy, 17th Edition. (Ed. by F.D. Burg, J.R. Ingelfinger, R.A. Polin, and A.A. Gershon) Philadelphia: W.B. Saunders, pp. 603-607.
- Bates, Michael D. (2003). The Potential of DNA Microarrays for the Care of Children. Journal of Pediatrics 142:235-239.
- Cohran, Valeria C. and Bates, Michael D. (2003). Leptin Signaling and Obesity: Weight and See. Gastroenterology 124:1546-1548.
- Bates, Michael D. and Deutsch, Gail H. (2003). Molecular Insights into Congenital Disorders of the Digestive System. Pediatric and Developmental Pathology 6:284-298.
- Bates, Michael D. and Balistreri, William F. (2004). Morphogenesis of the Liver and Biliary System. In: Nelson Textbook of Pediatrics, 17th Edition. (Ed. by Richard E. Behrman, Robert M. Kliegman, and Hal B. Jenson). Philadelphia: W.B. Saunders, pp. 1304-1308.
- Bates, Michael D.; Wells, James M.; and Venkatesh, Byrappa (2005). Comparative Genomics of the Hlx Homeobox Gene and Protein: Conservation of Structure and Expression from Fish to Mammals. Gene 352:45-56.
- Mikhalkevich, Natallia; Becknell, Brian; Caligiuri, Michael A.; Bates, Michael D.; Harvey, Richard; and Zheng, Wei-ping (2006). Responsiveness of Naïve CD4 T Cells to Polarizing Cytokine Determines the Ratio of Th1 and Th2 Cell Differentiation. Journal of Immunology 176:1553-1560.
- Erwin, Christopher R.; Jarboe, Marcus D.; Sartor, Maureen A.; Medvedovic, Mario; Warner, Brad W.; and Bates, Michael D. (2006). Developmental Characteristics of Adapting Small Intestine Crypt Cells. Gastroenterology 130:1324-1332.
- Bates, Michael D. (2006). Genetics of Anorectal Malformations. Pull-thru Network News 15(2):15-16.
- Bates, Michael D.; Dunagan, Dana T.; Welch, Lynn C.; Kaul, Ajay; and Harvey, Richard P. (2006). The Hlx Homeobox Transcription Factor Is Required Early in Enteric Nervous System Development. BMC Developmental Biology 6:33. [Link for free download]
- Falcone, Richard A.; Levitt, Marc A.; Peña, Alberto P.; and Bates, Michael D. (2007). Increased Heritability of Certain Types of Anorectal Malformations. Journal of Pediatric Surgery, 42:124-128.
- Becknell, Brian; Hughes, Tiffany L.; Freud, Aharon G.; Blaser, Bradley W.; Yu, Jianhua; Trotta, Rossana; Mao, Hsiaoyin C.; Caligiuri de Jesús, Marie L.; Alghothani, Mohamad; Benson, Don M., Jr.; Lehman, Amy; Jarjoura, David; Perrotti, Danilo; Bates, Michael D.; and Caligiuri, Michael A. (2007). The Hlx Homeobox Transcription Factor Negatively Regulates Interferon-γ Production in Monokine-Activated Natural Killer Cells. Blood, in press.
- Konikoff, Michael R. and Bates, Michael D. Applications of Human Genomics in Clinical Pediatrics. In: Genomics and Clinical Medicine (Ed. by D. Kumar). Oxford: Oxford University Press. In press.
