The research laboratory of Robert Tepper, MD, PhD focuses on lung structure and function as it relates to airway hyper-reactivity, as well as lung growth and development. Dr. Tepper directs a basic science laboratory in the Wells Center for Pediatric Research and an infant pulmonary physiology laboratory in James Whitcomb Riley Hospital for Children. These combined resources provide an opportunity for translational research. Focuses within the lab include: the interaction between atopic inflammation and airway reactivity; the effects of premature birth, maternal smoking during pregnancy, and preeclampsia on lung growth and development; and mechanisms to stimulate lung growth, such as mechanical strain and chronic hypoxia.
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The long-term research goals have been to understand the growth and development of the lung early in life both under normal and pathologic conditions, and to develop strategies to maximize lung function. Many of the state-of-the-art methodologies used to assess airway and parenchymal function in infants and toddlers were developed in the Infant Pulmonary Function Laboratory at James Whitcomb Riley Hospital for Children. These methodologies have enabled the Tepper Lab to improve understanding of early pulmonary disease in this difficult to evaluate, but critical period in life. Dr. Tepper’s earliest studies demonstrated airway obstruction in premature infants, even when infants were still mechanically ventilated in the newborn intensive care unit (NICU), as well as early results that corticosteroid treatment suppressed lung inflammation and improved airway function in these subjects.
Active Research
More recently, the Tepper Lab has focused upon the impaired development of the lung parenchyma (gas exchange) following premature birth and developed the technique to measure pulmonary diffusion capacity in infants. Premature birth can differentially impair airway and parenchymal function, as these two components of the lung have differing rates of growth and development during fetal and postnatal life, as well as differing potential for compensatory growth and development.
The Tepper Lab is challenging current paradigms regarding the definition of chronic lung disease of infancy (CLDI) by demonstrating the potential role for more precise phenotyping based on specific pulmonary pathophysiology and proteomic patterns with late respiratory outcomes. In the Wells Center, studies have employed a hyperoxia induced murine model of CLDI to evaluate the pulmonary pathophysiology and the accompanying effects upon the pulmonary vasculature and cardiac function, as well as promotion of asthma-like features through IL-33-dependent ILC2 responses.
Decrements in airway and parenchymal function can be present early in life from multiple etiologies, such as maternal smoking during pregnancy, premature birth, and preeclampsia (an anti-angiogenic fetal environment). Dr. Tepper’s laboratory has been evaluating mechanisms that could potentially prevent adverse effects of maternal smoking, and stimulate lung growth and development. Maternal smoking during pregnancy is associated with lower airway function in infants, as well as more frequent episodes of wheezing respiratory illnesses during infancy, and diagnosis of asthma as older children. The laboratory is evaluating whether extra daily vitamin C, taken by pregnant women who cannot quit smoking, can block the negative effects of smoking on the infant’s lung function and respiratory symptoms. The lab’s results suggest that Vitamin C produces a sustained improvement in infant lung function during first year of life, and this cohort is being followed to 5 years of age to determine whether there is a long-term change in the trajectory of lung growth and development. Additional studies include the assessment of epigenetic changes in placental tissue and the infants’ oral mucosal epithelia to evaluate molecular mechanisms for the effects of Vitamin C upon lung development.
Dr. Tepper’s laboratory has also undertaken two approaches to evaluate ways to stimulate lung growth: 1) chronic mechanical strain of the lung, which occurs with the application of continuous positive airway pressure (CPAP), and 2) chronic hypoxia, which occurs in subjects residing at high altitude. The research within the lab includes both animal models and clinical studies.
Current Research Funding
07/15/12 – 05/31/22
Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function
Goals: to determine whether extra daily vitamin C taken by pregnant women who cannot quit smoking, can block the negative effects of the smoking on the infant’s lung function and respiratory symptoms.
9/21/16-9/20/2021
Maternal Vitamin C Supplementation to decrease effects of smoking during pregnancy on infant lung function and health
Goals: Our cohort of infants of mothers who could not quit smoking during pregnancy and received extra daily vitamin C or Placebo are part of the national multi-center NIH cohorts participating in Environmental influences on Child Health Outcomes (ECHO).
09/15/15 – 05/31/19
Anti-Angiogenic Preeclamptic Milieu Impairs Infant Lung and Vascular Development
Goals: 1) Determine whether angiogenic circulating progenitor cells (CPCs) in cord blood are associated with the risk of premature infants developing chronic lung disease of infancy (CLDI) and whether post-natal CPCs and environment alters the relationship between cord blood CPCs and CLDI, and 2) Determine whether angiogenic CPCs in cord blood are associated with pulmonary pathophysiology at 6 months corrected-age and whether post-natal CPCs and environment alters the relationship between cord blood CPCs and pulmonary dysfunction.
7/01/15 – 6/30/20
CPAP Drives Lung Growth and Pulmonary Function in Moderately Preterm Primates
Goals: 1) Determine whether applying CPAP for 10 days stimulates lung growth, improves lung function, and suppresses airway reactivity in non-human moderately premature primates and whether these effects persist with subsequent lung growth and development, and 2) Identify pathways and mechanisms by which CPAP stimulates lung growth and improves lung function.
09/01/2018 – 08/31/2019
Physiological Phenotyping of Respiratory Outcomes in Infants Born Premature
Studies proposed are highly innovative, testing new ideas that challenge current paradigms regarding BPD definition and outcomes by demonstrating the potential role for more precise phenotyping based on novel measures relating specific pulmonary pathophysiology and proteomic patterns with late respiratory outcomes to better distinguish infants at risk for sustained respiratory disease during early childhood.
3/01/2017 – 8/30/2018
Hypoxia-dependent Epigenetic Modifications in the Pulmonary Vasculature
Goals: determine if in utero hypoxia results in epigenetic modifications in hypoxia-sensitive pathways in the lung vasculature that begin in utero and that persist until adulthood; determine if epigenetic modifications in utero are reversible and inducible when the post-utero environment is changed.
Recent Publications
For a full list of Dr. Tepper’s publications, find him on PubMed.
Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP): Rationale, design, and methods of a randomized, controlled trial of vitamin C supplementation in pregnancy for the primary prevention of effects of in utero tobacco smoke exposure on infant lung function and respiratory health. McEvoy CT, Milner KF, Scherman AJ, Schilling DG, Tiller CJ, Vuylsteke B, Shorey Kendrick LE, Spindel ER, Schuff R, Mitchell J, Peters D, Metz J, Haas D, Jackson K, Tepper RS, Morris CD. Contemporary clinical trials. 2017; 58:66-77.
Cumulative effects of neonatal hyperoxia on murine alveolar structure and function. Cox AM, Gao Y, Perl AT, Tepper RS, Ahlfeld SK. Pediatric Pulmonology. 2017; 52(5):616-624.
Neonatal hyperoxia promotes asthma-like features through IL-33-dependent ILC2 responses. Cheon IS, Son YM, Jiang L, Goplen NP, Kaplan MH, Limper AH, Kita H, Paczesny S, Prakash YS, Tepper R, Ahlfeld SK, Sun J. J Allergy Clin Immunol. 2017 Dec 15. S0091-6749(17)32871-3.
Chronic Hypoxia Accentuates Dysanaptic Lung Growth. Llapur CJ, Martínez MR, Grassino PT, Stok A, Altieri HH, Bonilla F, Caram MM, Krowchuk NM, Kirby M, Coxson HO, Tepper RS. American Journal of Respiratory and Critical Care Medicine. 2016; 194(3):327-32.
Increased Cardiac Output and Preserved Gas Exchange Despite Decreased Alveolar Surface Area in Rats Exposed to Neonatal Hyperoxia and Adult Hypoxia. Goss KN, Tepper RS, Lahm T, Ahlfeld SK. American Journal of Respiratory and Critical Care Medicine. 2015; 53(6):902-6.
Research Team
Research team members within the Wells Center include research technicians Amy Gao and Fredrick Herman. Additional research team members from the Riley Infant Pulmonary Function Laboratory include Christina Tiller, Michelle Cunningham and Jeffrey Bjerregaard.