department of developmental biology

Professor

Department of Molecular Biology and Pharmacology
Department of Obstetrics and Gynecology

Research Interests

The placental hormone human chorionic gonadotropin (CG), and the pituitary hormones lutropin (LH), follitropin (FSH), and thyrotropin (TSH) are a family of heterodimeric glycoproteins that share a common alpha subunit but differ in their hormone-specific subunits. One or more of these hormones is essential for gonadal development and maintaining pregnancy and thyroid function. Our laboratory is focused in two general areas:

1) Regulation and structure of the human placental hormone genes during development. There are projects designed to elucidate the sequences and cellular factors associated with the expression of these hormonal genes. Studies also include ongoing transgenic models for studying the regulated synthesis of hCG.

2) Structure-function studies. Using site-directed mutagenesis, we are studying the structural determinants that govern the unique post- translational modifications of the related placental and pituitary glycoprotein hormones. These hormones undergo specific modifications and have unique biologic activities. Together with DNA mediated transfection techniques, monoclonal antibody screening, and protein and carbohydrate characterization, we can determine: (a) the region in the hormone associated with unique biologic activity; (b) the region critical for subunit assembly; and (c) disulfide bonds for folding of these hormones and the sequences critical for the differential sorting of the pituitary hormones. Studies are also underway for determining the ligand determinants which are critical for signal transduction in vivo as well as disecting the structure of the gonadal receptors associated with the biological action of these hormones. Such information has been useful for designing clinically useful agents for treating infertility.

Boime Biosketch

Training:

• St. Louis College of Pharmacy, St. Louis, MO B.S. 1964 Pharmacology
• Purdue University, West Lafayette, IN M.S. 1966 Pharmacology
• Washington University, St. Louis, MO Ph.D. 1970 Pharmacology
  

Academic Positions:

• Professor, Departments of Pharmacology and Obstetrics/Gynecology, Washington University School of Medicine, 1981 - present
• Associate Professor, Departments of Pharmacology and Obstetrics/Gynecology, Washington University School of Medicine, 1977 - 1981
• Assistant Professor, Departments of Pharmacology and Obstetrics/Gynecology, Washington University School of Medicine, 1972 - 1977
• Postdoctoral Fellow of the American Cancer Society in the laboratory of Dr. Philip Leder, National Institutes of Health, Bethesda, Maryland, 1970 - 1972
  

Honors:

• Fellow of the American Cancer Society, 1970 - 1972
• U.S. Public Health Service, Research Career Development Award, 1977 - 1982
  

Review Panels:

• Population Research Committee of the NIH, 1991 - present
• Member of Biochemical Endocrinology Study Section, National Institutes of Health, 1983 - 1987
  

Editorial Board Memberships:

• Endocrinology (Associate Editor), 1991 -1992
• Journal of Biological Chemistry, 1981 -1990 & 1993 - present
• Placenta, 1985 - present
• Biology of Reproduction, 1990 - present

 

Selected Publications

Boime, I., Ben-Menahem, D., Kudo, M., Sugahara, T., Sato, A., and Hsueh, A.J.W. "Conversion of heterodimeric gonadotropins to genetically linked single chains: New approaches to structure-activity relationships and analog design," FSH Action and Intraovarian Regulation, (Fauser, B.J.C.M., Bennink, H.J.T.C, Evers, J.L.H., Rommerts, F.F.G., Schoemaker, J., and te Velde, E.R., eds.) Parthenon Publishing, Casterton Hall, U.K. 1997 :3-10.

Garcia-Campayo, V., Sato, A., Hirsch, B., Sugahara, T., Muyan, M., Hswueh, A.J.W., and Boime, I. "Design of stable biologically active recombinant lutropin analogs," Nature Biotech. 1997 15:663.

Ben-Menahem, D., Hyde, R., Pixley, M., Berger, P., and Boime, I. "Synthesis of multi subunit domain gonadotropin complexes: A model of alpha/beta heterodimer formation," Biochemistry 1999 38:15070.

Kanda, M., Joblonka-Shariff, A., Sato, A., Pixley, M.R., Bos, E., Hiro'oka, T., Ben-Menahem, D., and Boime, I. "Genetic fusion of an alpha subunit gene to the FSH and CG beta subunit genes: Production of a bifunctional protein," Mol. Endocrinol. 1999 13:1873.

Garcia-Campayo, V., and Boime, I. "Novel recombinant gonadotropins," Trends in Endocrinol. Metab. 2001 12:72-77.

Ben-Menahem, D., Joblonka-Shariff, A., Hyde, R., Pixley, M.R., Srivastava, S., Berger, P., Boime, I. "The Position of the alpha and beta subunits in a single chain gonadotropin analog affects the heterodimeric interaction of the subunits," J. Biol. Chem. in press.

 

Contact Information

Irving Boime
Department of Molecular Biology and Pharmacology
Washington University School of Medicine
Campus Box 8103
660 South Euclid Avenue
St. Louis, MO 63110
(314) 362-2556
iboime@wustl.edu

Developmental Biology Program Website

http://molecool.wustl.edu/DevBiol/