Protective role of CXCR7 in neonatal hyperoxia-induced systemic vascular dysfunction in adulthood

PROJECT SUMMARY/ ABSTRACT
With the improvement in perinatal and neonatal care, a new generation of preterm survivors are now reaching
adulthood who have increased incidence of cardiovascular morbidities. This a public health concern. Most
preterm infants are exposed to supraphysiological oxygen levels. Neonatal hyperoxia exposure in preterm infants
increases vascular stiffness in childhood, leading to hypertension, stroke and ischemic heart disease in adult
life. However, little is understood about the molecular mechanisms linking neonatal hyperoxia exposure and
systemic vascular stiffness. Currently, there are no strategies to prevent the long-term systemic vascular
complications seen in preterm infants. This proposal will provide insights into the underlying mechanisms that
drive neonatal hyperoxia-induced systemic vascular stiffness and will identify novel targets to reduce vascular
diseases in preterm survivors across their lifespan.
In this project, Dr. Benny proposes to determine the molecular mechanisms by which endothelial Chemokine
Receptor 7 (CXCR7) decreases neonatal hyperoxia-induced systemic vascular stiffness. Aim 1 will test the
hypothesis that endothelial CXCR7 decreases neonatal hyperoxia-induced systemic vascular stiffness by
suppressing Transforming Growth Factor-β signaling in smooth muscle cells. Aim 2 will test the hypothesis that
endothelial CXCR7 attenuates neonatal hyperoxia-induced smooth muscle cell fibrosis by downregulating
endothelial inflammasome signaling.
Dr. Benny is firmly committed to a career focused on investigating the early origins of vascular morbidities in
preterm survivors. Her long-term goal is to translate her experimental laboratory research into the development
of therapeutic strategies that could ameliorate the vascular morbidities in the preterm survivors. If these goals
are achieved, her work will have a lasting impact on the cardiovascular outcomes of the preterm survivors across
their lifespan. She is strongly supported in her career and research goals by her mentors and her division at the
University of Miami Miller School of Medicine. She currently holds a position as an Assistant Professor of
Pediatrics with 75% protected time for research, start-up funds for her laboratory, independent laboratory and
office space.
This K08 award will allow Dr. Benny to undertake formal scientific training in vascular injury and stiffness. Under
the guidance of her primary mentor, Dr. Omaida Velazquez, her co-mentor Dr. Roberto Vazquez-Padron and
her mentoring committee which includes Dr. Joshua Hare, Dr. Karen Young, Dr. Claudia Rodrigues and Dr. Shu
Wu, she is fully equipped to advance her skills in both in vivo and in vitro methodologies described for assessing
vascular injury and stiffness. In addition, she will achieve her training goals through a career development plan
that consists of intensive mentorship, participation in institutional scientific and career development seminars,
attendance and presentation at national meetings. Completion of this comprehensive training plan will provide
Dr. Benny with the skills and experience necessary to successfully compete for independent funding in the next
phase of her career.

Grant Number: 5K08HL153945-05
NIH Institute/Center: NIH
Principal Investigator: Merline Benny