Juan Sanchez-Esteban - Pediatrics Faculty Profile

Juan Sanchez-Esteban
Neonatologist • Assistant Professor, The Warren Alpert Medical School of Brown University
MD, Autonomous University of Barcelona, 1980
401-274-1122, x1383
jesteban@wihri.org

Normal lung growth and development during fetal life are critical for survival after birth. Premature infants are often born before sufficient lung maturation has occurred, and as a result, they experience a high rate of long term pulmonary complications. Understanding the mechanisms of fetal lung growth and development is a crucial step for design of preventive and therapeutic strategies.

Mechanical forces generated in the womb by repetitive breathing-like movements and by fluid distension of the fetal lung are essential for normal lung development. The staff in Dr. Esteban’s laboratory is interested in understanding the mechanisms by which pulmonary cells sense these mechanical signals to promote lung maturation.

Using an in vitro system to simulate mechanical forces in utero, the researchers have previously found that mechanical strain induces fetal lung type II cell maturation. This process is mediated via the extracellular-regulated protein kinase (ERK) pathway. In addition, they have identified roles for the epidermal growth factor receptor (EGFR) and specific integrin subtypes as mechanosensors during alveolar development. Future studies, using twisting magnetic beads device to stimulate specific receptors and transgenic mice, will determine how these receptors interact to each other and identify proteins activated by strain that induce lung development.

Selected Publications
• Sanchez-Esteban J., Wang Y, Gruppuso P.A., Rubin L.P. Mechanical stretch Induces Fetal Type II Cell Differentiation via an EGFR-ERK Signaling Pathway. Am.J.Resp.Cell Mol.Biol 30 (1): 76-83, 2004.
• Sanchez-Esteban J., Wang Y., Cicchiello L., Rubin L.P. Cyclic Mechanical Stretch Inhibits Cell Proliferation and Induces Apoptosis in Fetal Rat Lung Fibroblasts. Am. J. Physiol Lung Cell Mol Physiol 282(3): L448-56, 2002.
• Sanchez-Esteban J., Cicchiello L., Tsai S.W., Wang Y., Williams L.K., Torday J.S., Rubin L.P. Mechanical Stretch Promotes Alveolar Epithelial Type II Cell Differentiation. J. Appl. Physiol. 91: 589-595, 2001.