Abstract

description): This K08 award will allow the candidate to obtain the scientific expertise and to conduct studies that will advance understanding of the functions of selected placental peptidases. Specifically, she will test hypotheses about the mechanisms by which alterations in the enzymes that process and metabolize Endothelin-1 are related to the pathogenesis of pre-eclampsia and pre-term labor and by which alterations in the carboxypeptidases that process a variety of peptide hormones and growth restriction.
Specific aim 1 will test the hypothesis that two closely related metalloendopeptidases, endothelin converting enzyme-1 (ECE-1) and neutral endopeptidase (NEP), function in the regulation of levels of endothelin-1 (ET-1) in the placenta and that ET-1 functions as a common pathway in the pathogenesis of pre-eclampsia and pre-term labor.
Aim 2 will test the hypothesis that recently identified members of the carboxypeptidase E family, highly concentrated in the rat placenta, also function as peptide processing enzymes in the human placenta.
Specific aim 3 will test the hypothesis that the novel placental proteins also have nonenzymatic functions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD001209-05
Application #
6520604
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Ilekis, John V
Project Start
1998-04-01
Project End
2004-12-31
Budget Start
2002-04-01
Budget End
2004-12-31
Support Year
5
Fiscal Year
2002
Total Cost
$85,158
Indirect Cost

  Institution

Name
Montefiore Medical Center (Bronx, NY)
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10467

  Publications

Munnangi, S; Gross, S J; Madankumar, R et al. (2014) Pregnancy associated plasma protein-A2: a novel biomarker for Down syndrome. Placenta 35:900-6
Sundaram, Sruthi; Ashby Jr, Charles R; Pekson, Ryan et al. (2013) N,N-dimethylacetamide regulates the proinflammatory response associated with endotoxin and prevents preterm birth. Am J Pathol 183:422-30
Wang, Wei; Yen, Haoting; Chen, Chih-Hung et al. (2010) Prevention of inflammation-associated preterm birth by knockdown of the endothelin-1-matrix metalloproteinase-1 pathway. Mol Med 16:505-12
Wang, Wei; Yen, Haoting; Yen, Hauting et al. (2008) The endothelin-converting enzyme-1/endothelin-1 pathway plays a critical role in inflammation-associated premature delivery in a mouse model. Am J Pathol 173:1077-84
Olgun, Nicole; Patel, Hardik J; Stephani, Ralph et al. (2008) Effect of the putative novel selective ETA-receptor antagonist HJP272, a 1,3,6-trisubstituted-2-carboxy-quinol-4-one, on infection-mediated premature delivery. Can J Physiol Pharmacol 86:571-5
Vu, Thanh-Danae; Yun Feng; Placido, Jessica et al. (2008) Placental matrix metalloproteinase--1 expression is increased in labor. Reprod Sci 15:420-4
Koscica, Karen L; Ananth, Cande V; Placido, Jessica et al. (2007) The effect of a matrix metalloproteinase inhibitor on inflammation-mediated preterm delivery. Am J Obstet Gynecol 196:551.e1-3
Koscica, Karen L; Sylvestre, Georges; Reznik, Sandra E (2004) The effect of phosphoramidon on inflammation-mediated preterm delivery in a mouse model. Am J Obstet Gynecol 190:528-31
Feng, Yun; Reznik, Sandra E; Fricker, Lloyd D (2002) ProSAAS and prohormone convertase 1 are broadly expressed during mouse development. Brain Res Gene Expr Patterns 1:135-40
Novikova, E; Fricker, L D; Reznik, S E (2001) Metallocarboxypeptidase Z is dynamically expressed in mouse development. Mech Dev 102:259-62

Showing the most recent 10 out of 14 publications