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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.
Transcriptional Control of Human Placental DifferentiationNIH HD-065339P.I.- Stuart Handwerger
Schroeder, JK, Kessler, CA, Handwerger, S. Critical role for TWIST1 in the induction of human uterine decidualization. Endocrinology. 152:4368–4376. 2011.
Sherafat-Kazemzadeh, R, Schroeder, JK, Kessler, CA, Handwerger, S. Parathyroid hormone-like hormone (PTHLH) represses decidualization of human uterine fibroblast cells by an autocrine/paracrine mechanism. J Clin Endocrinol Metab. 96:509–514. 2011.
Tang, M, Naidu, D, Hearing, P, Handwerger, S, Tabibzadeh, S. LEFTY, a member of the transforming growth factor-beta superfamily, inhibits uterine stromal cell differentiation: a novel autocrine role.Endocrinology. 151:1320–1330. 2010.
Handwerger, S. New insights into the regulation of human cytotrophoblast cell differentiation. Mol Cell Endocrinol. 323:94–104. 2010.
Hubert, MA, Sherritt, SL, Bachurski, CJ, Handwerger, S. Involvement of transcription factor NR2F2 in human trophoblast differentiation. PLoS One. 5:e9417. 2010.
Kessler, CA, Bachurski, CJ, Schroeder, J, Stanek, J, Handwerger, S. TEAD1 inhibits prolactin gene expression in cultured human uterine decidual cells. Mol Cell Endocrinol. 295:32–38. 2008.
Repaske, DR, Handwerger, S. Making the transition from pediatric to adult endocrinology services.Nat Clin Pract Endocrinol Metab. 4:492–493. 2008.
Stuart Handwerger, MD513-636-4209
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