Handwerger Lab Research
Research in the Handwerger laboratory focuses on the molecular mechanisms involved in human placental development and the regulation of placental hormones involved in the control of fetal growth and development. Using an in vitro model of human villus cytotrophoblast differentiation, the laboratory has used genome-wide microarray analyses to delineate genes that are induced and repressed during the differentiation of cytotrophoblast cells to a syncytiotrophoblast cell phenotype. Knockdown and overexpression experiments identified several transcription factors, including TFAP2A, FOXF1 and NR2F2, that act as key regulators of the differentiation process. Transient transfection and other studies also delineated several putative signaling pathways and interactions involved in transcriptional regulation. Additional experiments have focused on the transcription factors and signaling pathways implicated in the regulation of human placenta lactogen (hPL) and human growth hormone variant (hGH-v), two proteins expressed by syncytiotrophoblast cells that modulate fetal growth and metabolism.
Current projects
- Delineation of the downstream targets of TFAP2A, FOXF1 and NR2F2 during trophoblast differentiation using ChIP-seq analyses.
- Studies of the roles of the transcription factors ETS1 and FOXO1 in trophoblast differentiation using knockdowns with specific lentivirus shRNAs.
- Immunohistchemical studies of TFAP2A, FOXF1 and NR2F2 protein expression in normal and pathologic placentas.
Research support
Transcriptional Control of Human Placental Differentiation
NIH HD-065339
P.I.- Stuart Handwerger
