In the last 20 years the prevalence of asthma has doubled and it now affects 10% of the population in the United States. The susceptibility to allergic asthma varies greatly in the population exposed to allergens. Gene-environment interaction may play an important role in pathogenesis of asthma. Our long-term objective is to understand the host factors that regulate susceptibility to allergens and the pathogenesis of asthma. Such an understanding is vital for developing new intervention strategies. We recently reported a novel host factor, nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), that may play a critical role in determining susceptibility to allergic asthma. Nrf2 is a basic leucine zipper transcription factor that determines the severity to asthma in mice models by regulating environmental stress response that includes cellular antioxidants. Disruption of Nrf2 in mice leads to severe asthma in response to sensitization and challenge by variety of allergens such as ovalbumin and ragweed extract. The exaggerated asthmatic response in Nrf2-disrupted mice in response to allergen involves increased oxidative stress and pronounced infiltration of eosinophils into the lungs, greater T helper 2 cells and cytokines (IL-4, IL-13), antigen-specific IgE, mucus cell hyperplasia, airway hyperresponsiveness. Thus, Nrf2 is a critical regulator of asthma pathogenesis.Our central hypothesis is that Nrf2 dependent compensatory transcriptional program regulate the environmental stress response that protects against allergen-induced asthma by decreasing oxidative stress in the airway epithelium and Th2 effector cells that in turn inhibits cytokine and chemokine expression. Conversely, disrupted or suboptimal Nrf2 activity causes increased oxidative stress and asthmatic response.
Specific Aim 1 : To investigate the regulation of asthma by Nrf2 activity in the airway epithelium.
Specific Aim 2 : To investigate the regulation of asthma by Nrf2 activity in T effector cells.
Specific aim 3 : To test the hypothesis that genetic variation in Nrf2 and its target antioxidant genes is associated with susceptibility to childhood asthma and atopy.
Specific Aim 4 : To test the hypothesis that enhancing Nrf2 activity can attenuate asthma.The proposal will focus on investigating Nrf2 dependent regulation of asthma pathogenesis and strive to develop a preclinical intervention strategy by targeting this transcription factor for decreasing asthma in the susceptible individuals in the population.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
United States
Zip Code
Wu, Tianshi David; Eakin, Michelle N; Rand, Cynthia S et al. (2018) In-Home Secondhand Smoke Exposure Among Urban Children With Asthma: Contrasting Households With and Without Residential Smokers. J Public Health Manag Pract :
Wu, Tianshi David; Brigham, Emily P; Peng, Roger et al. (2018) Overweight/obesity enhances associations between secondhand smoke exposure and asthma morbidity in children. J Allergy Clin Immunol Pract 6:2157-2159.e5
Grant, Torie; Aloe, Charles; Perzanowski, Matthew et al. (2017) Mouse Sensitization and Exposure Are Associated with Asthma Severity in Urban Children. J Allergy Clin Immunol Pract 5:1008-1014.e1
McCormack, Meredith C; Paulin, Laura M; Gummerson, Christine E et al. (2017) Colder temperature is associated with increased COPD morbidity. Eur Respir J 49:
Peters, Kamau O; Williams, D' Ann L; Abubaker, Salahadin et al. (2017) Predictors of polycyclic aromatic hydrocarbon exposure and internal dose in inner city Baltimore children. J Expo Sci Environ Epidemiol 27:290-298
Nnodum, Benedicta Nneoma; McCormack, Meredith C; Putcha, Nirupama et al. (2017) Impact of Physical Activity on Reporting of Childhood Asthma Symptoms. Lung 195:693-698
Paulin, Laura M; Williams, D 'Ann L; Peng, Roger et al. (2017) 24-h Nitrogen dioxide concentration is associated with cooking behaviors and an increase in rescue medication use in children with asthma. Environ Res 159:118-123
Miele, Catherine H; Jaganath, Devan; Miranda, J Jaime et al. (2016) Urbanization and Daily Exposure to Biomass Fuel Smoke Both Contribute to Chronic Bronchitis Risk in a Population with Low Prevalence of Daily Tobacco Smoking. COPD 13:186-95
Kolahdooz, Fariba; Butler, Jennie L; Christiansen, Karina et al. (2016) Food and Nutrient Intake in African American Children and Adolescents Aged 5 to 16 Years in Baltimore City. J Am Coll Nutr 35:205-16
McCormack, Meredith C; Belli, Andrew J; Waugh, Darryn et al. (2016) Respiratory Effects of Indoor Heat and the Interaction with Air Pollution in Chronic Obstructive Pulmonary Disease. Ann Am Thorac Soc 13:2125-2131

Showing the most recent 10 out of 100 publications