Clinical Assistant Professor
Pathology and Laboratory Medicine
Rutgers Biomedical and Health Services
Dr. Carayannopoulos was involved in the cloning of a novel glucose transporter in Dr. Kelle Moley’s lab in Obstetrics and Gynecology. She was very productive and published 15 papers, 3 of which described work directly involved with her activities on the BIRCWH project. After completely BIRCWH training at Washington University, she accepted a position as Clinical Assistant Professor in the Department of Pathology and Laboratory Medicine of UMDNJ-Robert Wood Johnson Medical School. She is the Director of Clinical Chemistry at UMDNJ-Robert Wood Johnson Medical School. Her current research focuses on the role of intralipid on hyperbilirubinemia in preterm infants. She recently received an RO3 award to support this work.
BIRCWH Scholar from 07/01/2004 until 12/31/2008
Deciphering the Molecular Mechanisms Involved in Diabetes Associated Congenital Malformations
Poor glycemic control during pregnancy results in compromised pregnancy outcome. While morbidity and mortality are significantly reduced when glucose is tightly controlled throughout gestation, women with type 1, type 2 and gestational diabetes continue to be at an increased risk for pregnancy associated complications. Work from our laboratory has shown that maternal hyperglycemia during the preimplantation period results in down-regulation of the embryonically expressed glucose transporters, Gluts 1-3 . This decrease in transporter expression leads to a significant drop in intraembryonic free glucose and an increase in apoptosis in the blastocyst. We hypothesize that this induced apoptosis results in loss of key progenitor cells that manifests later in pregnancy as a malformation or miscarriage. In an effort to decipher the mechanisms involved in hyperglycemia induced apoptosis, we propose to establish embryonic stem cell (ES) lines from Glut1 antisense (G1AS) transgenic mice. These mice express decreased levels of Glut1 due to the expression of a Glut1 antisense transcript . The phenotype of mice homozygous for the transgene is similar to what we have observed in mice exposed to hyperglycemia. They experience a dramatic increase in major congenital malformations (35% in G1AS x G1AS matings vs 0% in the nontransgenic (NT) matings), which include neural tube defects and caudal regression syndrome, both malformations seen in the offspring of diabetic mothers. These G1AS ES cell lines will serve as an in vitro cell culture system that will allow us to define what signaling pathways are involved in hyperglycemia induced apoptosis. These cell lines will further allow us to determine how alterations in these signaling pathways early in development could result in congenital malformations.
- Can embryonic stem (ES) cell lines established from Glut1AS (G1AS) transgenic mice serve as an in vitro model for blastocysts exposed to hyperglycemia?
- Using gene-chip analysis, can we define what genes are differentially expressed in G1AS ES cell lines (Tg/Tg vs Tg/+ vs +/+)?
- Using ES cell differentiation techniques, can we determine how decreased Glut1 expression can result in congenital malformations?