Cristina M. Alvira
Academic Appointments
- Assistant Professor, Pediatrics - Critical Care
- Member, Child Health Research Institute
Key Documents
Contact Information
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Clinical Offices
Pediatric Intensive Care 725 Welch Rd 2 East Palo Alto, CA 94304 Tel Work (650) 497-8850 Fax (650) 725-8343Practices at Lucile Packard Children's Hospital
- Academic Offices
Personal Information Email
Professional Overview
Clinical Focus
- Intensive Care, Pediatric
- Pediatric Critical Care Medicine
Honors and Awards
- Fellow to Faculty Transition Grant, American Heart Association (2008-2013)
- Pediatric Clerkship Honor Roll for Teaching, Lucile Packard Children's Hospital at Stanford (2007)
- Travel Award, Society for Pediatric Research (2004)
- Travel Award, Western Society for Clinical Investigation (2004)
- Excellence in Clinical Medicine, Louis Weinstein Prize (1999)
- Member, Alpha Omega Alpha National Honor Society (1998)
Professional Education
| Fellowship: | Stanford University Medical Center CA (2005) |
| Internship: | Stanford University Medical Center CA (2000) |
| Residency: | Stanford University Medical Center CA (2002) |
| Medical Education: | Tufts University MA (1999) |
| Board Certification: | Pediatric Critical Care Medicine, American Board of Pediatrics (2006) |
| BS: | Tufts University, Biology (1995) |
Graduate & Fellowship Program Affiliations
Internet Links
Scientific Focus
Current Research Interests
Secondary septation, the process that marks the alveolar phase of lung development,involves the coordinated activities of multiple different cell types within the lung. Secretion of extracellular matrix components, proliferation and migration of myofibroblasts and epithelial cells, and pulmonary capillary angiogenesis, have been identified as key players in this process. However, in contrast to the identification of multiple transcription factors controlling branching morphogenesis during the early stages of lung development, the regulators that control and coordinate the individual components of alveolarization remain unknown. The nuclear factor kappa-B (NFkB) family of transcription factors plays a key role in regulating cell survival, differentiation, and inflammation, however, a role in lung development has not been previously identified. A main focus of our work is to define a novel function for NFkB in regulating postnatal lung development using mouse models and primary cell lines.
Postnatal pulmonary angiogenesis is essential for alveolarization. We have recently demonstrated a high degree of constitutive NFkB signaling in primary pulmonary endothelial cells (PEC) isolated from neonatal mice as compared to those isolated from adult mice. Furthermore, inhibiting constitutive NFkB activity in the neonatal PEC with either pharmacologic inhibitors or RNA interference, blocked PEC survival, decreased proliferation, and impaired in vitro angiogenesis. In this project we are utilizing RNAi to block the individual components of the NFkB pathway, gene expression analysis, and endothelial specific conditional knock-out mice in order to identify novel NFkB mediated targets that are essential for postnatal pulmonary angiogenesis.
In a separate but related project, we are exploring pathways which help to preserve normal lung development in the setting of lung injury. Both local and systemic infections can injure the lung. Clinical and experimental evidence suggests that unique pathways may exist that serve to protect the immature lung from severe inflammation, and potentially allow for a greater regeneration after injury. Using a murine model of acute respiratory distress syndrome induced by the administration of systemic lipopolysaccharide, we are exploring the molecular mechanisms that serve to protect the lung against injury, and identify how these mechanisms are distinct in immature and mature animals. We believe that the information learned from these studies will be clinically relevant to a broad number of pulmonary diseases including bronchopulmonary dysplasia, asthma, ARDS, and emphysema.
Publications
- Inhibiting NF-κB in the developing lung disrupts angiogenesis and alveolarization. Am J Physiol Lung Cell Mol Physiol. 2012; (10): L1023-36
- Voltage-dependent anion channel-2 interaction with nitric oxide synthase enhances pulmonary artery endothelial cell nitric oxide production. Am J Respir Cell Mol Biol. 2012; (5): 669-78
- Inhibition of transforming growth factor β worsens elastin degradation in a murine model of Kawasaki disease. Am J Pathol. 2011; (3): 1210-20
- Rho kinase modulates postnatal adaptation of the pulmonary circulation through separate effects on pulmonary artery endothelial and smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2010; (6): L872-8
- Nuclear factor-kappaB activation in neonatal mouse lung protects against lipopolysaccharide-induced inflammation. Am J Respir Crit Care Med. 2007; (8): 805-15
- Hypoxia-inducible factor-1α in pulmonary artery smooth muscle cells lowers vascular tone by decreasing myosin light chain phosphorylation. Circ Res. 2013; (9): 1230-3
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