Irving Boime, Ph.D.

Professor
Developmental Biology
Obstetrics and Gynecology

Biochemistry, Biophysics, and Structural Biology Program
Molecular Cell Biology Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-362-2556

  • 314-362-2519

  • 314-361-3560

  • 8103

  • 3909 South Building, 3rd Floor

  • iboime@wustl.edu

  • http://boimelab.wustl.edu

  • biochemistry, carbohydrate, protein structure, signal transduction, intracellular trafficking

  • Placental and pituitary hormone genes

Research Abstract:

Human chorionic gonadotropin (CG), lutropin (LH), follitropin (FSH), and thyrotropin (TSH) are a family of heterodimeric glycoprotein hormones that share a common α subunit but differ in their hormone-specific β subunits. One or more of these hormones is essential for gonadal development, and for maintaining pregnancy and thyroid function. Using site-directed mutagenesis, our laboratory investigates 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, the laboratory is examining the regions critical for chaperone interactions in the folding and the differential sorting of these heterodimeric hormones. Studies are also underway for determining the ligand determinants that are responsible for the transducing signals in the hormone-receptor complex. A critical feature of these hormones is their unique secretion patterns. LH is secreted through a regulated secretory pathway, i.e. it is released by secretagogue, whereas FSH is primarily secreted constitutively. The oligosaccharides on these glycoproteins are hormone specific. We are currently testing models addressing the hypothesis that the carbohydrates play a critical role in FSH/LH sorting. FSH-LH β chimeras and point mutants are currently designed to identify sequences that govern their unique secretion patterns. Informative LH and FSH variants in cell-culture assays will be expressed in pituitaries from transgenic mice. The ability to reroute FSH and LH in vivo would represent an important model for gonadal dysfunction and potentially provide a novel way to examine normal and ultimately pathophysiological events in the human reproductive tract.

Selected Publications:

Pearl C, Boime I. Sulfation of LH does not affect intracellular trafficking. Mol & Cell Endo. 2009 309:76-81.

Fauser BC, Mannaerts BM, Devroey P, Leader A, Boime I and Baird DT. Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency. Hum. Reprod. Update 2009.

Jablonka-Shariff A, Boime I. Secretory trafficking signal encoded in the carboxyl-terminal region of the CGb subunit. Molec. Endocrinol. (Baltimore, MD) 2009 23: 316-23.

Jablonka-Shariff A, Pearl CA, Comstock A, Boime I. A Carboxyl-terminal Sequence in the Lutropin b subunit contributes to the sorting of Lutropin to the Regulated Pathway. J. Biol. Chem 2008 283(17): 11485-11492.

Jablonka-Shariff A, Garcia-Campayo V, Boime I. Evolution of lutropin to chorionic gonadotropin generates a specific routing signal for apical release in vivo. J Biol Chem 2002 277:879-882.

Last Updated: 8/3/2011 1:49:06 PM

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