This Program Project entitled, """"""""Studies of Conadotropins"""""""" is composed of four research projects and two core facilities. Its central theme is to improve the understanding of gonadotropin structure-function relationships and to improve methods to quantify gonadotropins in studies of human reproduction. The first research project entitled, """"""""Hormone Structure and Function"""""""" will be directed by Dr. William Moyle and applies the techniques of genetic engineering to make modifications in gonadotropin gene structure, so the expressed products can be evaluated for alterations of function. Alterations to be studied include hormone receptor binding and biological activity, and it is expected that the results will define the amino acids that contribute to the structure of antibody binding sites. The second research project entitled, """"""""Protein Chemistry of Gonadotropins and Fragments"""""""" will be directed by Dr. Steven Birken and applies the techniques of protein chemistry to the genetically-altered proteins produced by Project I and also attempts to solve the location of the disulfide bridges in the native structure of Gonadotropin subunits, as well as the origins and structure of gonadotropin fragments that are employed as disease markers. Project III entitled, """"""""Biophysical and Immunochemical Studies of Gonadotropins"""""""" will be directed by Dr. Canfield, and this will serve as the interface of all disciplines in the program with a special emphasis on protein physical chemistry and immunology. The goal is to increase understanding of the three-dimensional structure of gonadotropins by three-dimensional model building, NMR studies, protein crystallography experiments, and by producing novel antibodies to gonadotropins, whose defined epitopes provide useful information about the surface arrangement of amino acids. Project IV entitled, """"""""Clinical Applications of Gonadotropin Measurement"""""""" will be directed by Dr. John O'Connor, and its goal is to apply immunologic techniques to improve clinical research measurements related to early pregnancy loss, ovulation, and other reproductive events. This program will also include an Administrative Core Facility, directed by Dr. Canfield, and a Tissue Culture and Hybridoma Core, directed by Dr. Alexander Krichevsky. Both will provide services to all four research projects.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD015454-12
Application #
3096779
Study Section
Population Research Committee (HDPR)
Project Start
1981-07-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
12
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Birken, S; Krichevsky, A; O'Connor, J et al. (1999) Development and characterization of antibodies to a nicked and hyperglycosylated form of hCG from a choriocarcinoma patient: generation of antibodies that differentiate between pregnancy hCG and choriocarcinoma hCG. Endocrine 10:137-44
Kovalevskaya, G; Birken, S; Kakuma, T et al. (1999) Early pregnancy human chorionic gonadotropin (hCG) isoforms measured by an immunometric assay for choriocarcinoma-like hCG. J Endocrinol 161:99-106
Lin, W; Ransom, M X; Myers, R V et al. (1999) Addition of an N-terminal dimerization domain promotes assembly of hCG analogs: implications for subunit combination and structure-function analysis. Mol Cell Endocrinol 152:91-8
Kovalevskaya, G; Birken, S; Kakuma, T et al. (1999) Evaluation of nicked human chorionic gonadotropin content in clinical specimens by a specific immunometric assay. Clin Chem 45:68-77
Ulaner, G A; Chuang, J; Lin, W et al. (1999) Desensitization and resensitization of lutropin receptors expressed in transfected Y-1 adrenal cells. J Endocrinol 163:289-97
O'Connor, J F; Kovalevskaya, G; Birken, S et al. (1998) The expression of the urinary forms of human luteinizing hormone beta fragment in various populations as assessed by a specific immunoradiometric assay. Hum Reprod 13:826-35
Lunardi-Iskandar, Y; Bryant, J L; Blattner, W A et al. (1998) Effects of a urinary factor from women in early pregnancy on HIV-1, SIV and associated disease. Nat Med 4:428-34
Elliott, M M; Kardana, A; Lustbader, J W et al. (1997) Carbohydrate and peptide structure of the alpha- and beta-subunits of human chorionic gonadotropin from normal and aberrant pregnancy and choriocarcinoma. Endocrine 7:15-32
Campbell, R K; Bergert, E R; Wang, Y et al. (1997) Chimeric proteins can exceed the sum of their parts: implications for evolution and protein design. Nat Biotechnol 15:439-43
Cosowsky, L; Lin, W; Han, Y et al. (1997) Influence of subunit interactions on lutropin specificity. Implications for studies of glycoprotein hormone function. J Biol Chem 272:3309-14

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