The Division of Pediatric Pulmonology directs investigator-initiated basic and clinical research programs related to asthma, cystic fibrosis and bronchopulmonary dysplasia. Faculty research is funded by the National Institutes of Health and Cystic Fibrosis Foundation. Areas of study include:
- Viral-induced exacerbations of asthma and other chronic airways diseases
- Contribution of early-life respiratory viral infections in the development of asthma
- Matricellular proteins in the pathogenesis of asthma and bronchopulmonary dysplasia
- Interactive effects of diesel exhaust and respiratory viral infection on asthmatic children
- Promoting activity among children with asthma in Detroit
- Role of viral and bacterial co-infection in the pathogenesis of cystic fibrosis lung disease
- Influence of the airway microbiome on nontuberculous mycobacterial infection in cystic fibrosis
- Interventions to improve adherence in children with cystic fibrosis
- Studies to improve the cystic fibrosis newborn screening parental notification process
- Matricellular proteins in the pathogenesis of asthma and bronchopulmonary dysplasia
- Damage-associated molecular patterns and priming of the immune system in bronchopulmonary dysplasia
- Role of adipose-tissue macrophages in the pathogenesis of obesity-associated diseases such as metabolic syndrome and diabetes
Marc B. Hershenson, M.D.
Professor of Pediatrics
The focus of my research is chronic airways disease in children, including asthma, cystic fibrosis and bronchopulmonary dysplasia. Specific research projects include:
Viral-induced asthma exacerbations. My laboratory developed the first mouse model of rhinovirus-induced asthma exacerbations. Using this model, we found for the first time that rhinovirus interacts with not only airway epithelial cells but also non-resident airway macrophages, perhaps explaining the brisk inflammatory response to viral infection in asthmatics compared to normal subjects. We have also found interactions between rhinovirus and macrophages in human airways. We are currently interactions between rhinovirus and Toll-like receptors (Figure) in rhinovirus-induced airway responses. Funding: NIH R01 HL134369 and HL81420
Early-life viral infections in the development of asthma.
Funding: NIH R21 AI114220
Early-life wheezing-associated respiratory viral infections have been recognized to be a harbinger of asthma in young children. However, it is unclear whether viral infections, in combination with other factors, actually contribute to asthma development, or whether viral infection simply unmasks asthma that was already present. To study this, my laboratory developed the first immature mouse model of rhinovirus infection.
We found that early-life infection of immature mice with rhinovirus causes a long-lasting asthma phenotype consisting of mucous metaplasia and airways hyperresponsiveness which is dependent on IL-13, IL-25 and type 2 innate lymphoid cells (Figure).
Interestingly, the pro-asthmatic effect of virus is limited to mice that are less than 8 days of age. These studies show the importance of developmental stage in the response to respiratory viral infections. Funding: NIH R01AI120526
S-nitrosothiol-based rinse/aerosol solutions for treatment/prevention of rhinosinusitis. The purpose of the research being proposed is to develop a highly effective nasal rinse that can treat chronic rhinosinusitis (CRS) in an entirely new way.In coordination with Drs. Uma Sajjan, Mark Meyerhoff and NOTA Laboratories, our team plans to: 1) identify and optimize a formulation of S-nitrosoglutathione (GSNO) and examine the rates of NO release using chemiluminescence measurements; and 2) test the ability of such NO-releasing solutions to disrupt bacterial biofilms on mucociliary-differentiated primary sinus epithelial cell cultures. Funded by NIH R41 AI120443
J. Kelley Bentley, Ph.D.
Associate Research Scientist, Department of Pediatrics
The focus of my research is matricellular proteins and their role in the pathogenesis of asthma and bronchopulmonary dysplasia. Matricellular proteins are non-structural extracellular matrix proteins that modulate cell-matrix interactions, thereby influencing fiber deposition, cell adhesion, migration, proliferation and survival.
One particular matricellular protein, periostin, is expressed in the airways of patients with IL-13-mediated allergic asthma (Figure). With Dr. March Hershenson we have recently shown in mice that periostin is not only a biomarker, but also required for house dust mite-induced allergic airways disease. Thus, periostin represents a new therapeutic target for asthma. Funding: NIH R01 HL079339
Lindsay J. Caverly, M.D.
Clinical Lecturer, Dept of Pediatrics
Pubmed Search for Caverly LJ
The focus of my research is the airway microbiome in cystic fibrosis patients with non-tuberculous mycobacterial infection. The prevalence of non-tuberculous Mycobacteria (NTM) infection is increasing in children with cystic fibrosis.
This is a particularly challenging infection, as treatment may have significant side effects (primarily ototoxicity) and may not be completely effective. Also, it is difficult to identify which patients require treatment, as some patients suffer a progressive deterioration of lung disease while others clear the bacteria without treatment. My goal is to identify infectious and inflammatory changes in cystic fibrosis airways that are predictive of NTM acquisition and disease course. Funding: NIH K12 HD028820 (V. Castle, PI)
Toby Crowe Lewis, M.D., M.P.H.
My research focuses on asthma epidemiology and airborne exposures. Specific research projects include:
Interactive effects of diesel exhaust and respiratory viral infection on asthmatic children.
My research team is testing the general hypothesis that traffic-associated air pollution, specifically diesel exhaust, and respiratory viral infections combine to induce exaggerated asthmatic responses in children with asthma. We are determining whether traffic-associated air pollution (Figure) increases susceptibility to viral upper respiratory tract infections, and whether combined exposures to pollutants and upper respiratory tract infections elicit augments inflammatory and oxidative stress responses, leading to worse clinical asthma outcomes. Funding: NIH R01 ES016769
With Dr. Marc Hershenson, my laboratory is also examining the pathogenesis of viral-induced asthma exacerbations in children with asthma. We collect nasal aspirates before and during respiratory viral infections. We analyze the aspirates for the presence of virus and expression of host mRNAs, proteins and micro RNAs, and correlate our findings with changes in asthma symptoms and pulmonary function. Funding: NIH R21 AI114220
Promoting activity among children with asthma in Detroit.
My research team also studies community-based health behavior interventions to improve asthma care. Children with asthma in Detroit face barriers to more active lifestyles. We currently plan a multi-faceted program to promote exercise in inner-city children with asthma which we hypothesize will improve asthma-related quality of life.
Carey N. Lumeng, M.D., Ph.D.
Associate Professor of Pediatrics
Obesity threatens the health of children and adults in the U.S. due its strong association with diseases such as metabolic syndrome and Type 2 diabetes. My laboratory studies the origins of adipose tissue inflammation with obesity. My current research projects include:
Regulation of adipose tissue inflammation by antigen presenting cells. Recently, studies have demonstrated that T cells partner with adipose tissue macrophages (Figure) to cause inflammation in obese adipose tissue. My laboratory is testing the hypothesis that adipose tissue macrophages function as antigen presenting cells to communicate with and activate inflammatory CD4+ T cells in fat. Identification of the types of cell-cell communications that regulate inflammation in adipose tissue can identify novel points for intervention to uncouple obesity from its negative effects on health. Funding: NIH R01 DK090262
Inflammatory Effects of Post-Natal Overnutrition. Rapid post-natal growth is a risk factor for obesity and cardiometabolic disease. Using animal models we are evaluating the influence of post-natal overnutrition on innate immunity. Funding: NIH R21 HD086696
Obesity Induced Effects on Hematopoiesis. The lab seeks to understand how obesity influences myeloid cell production from the bone marrow compartment. Funding: American Diabetes Association Career Development Award.
Samya Z. Nasr, M.D.
My research studies the delivery of health care in children with cystic fibrosis. Specific research projects include:
Interventions to improve adherence in children with cystic fibrosis. This is a longitudinal prospective trial looking at the impact of home lung function monitoring on adherence, clinical outcomes and quality of life in children 12-21 years of age with CF. Participants are assigned to the Spiro PD® personal spirometer to monitor their lung function once a week from home. Prescription refill histories for the duration of the study and in the 12-months prior to enrollment will be compared to gauge the impact of our intervention on medication adherence. Lung function results, BMI, frequency of pulmonary exacerbations and responses to the CFQ-R will be used as health outcome and quality of life measures. Funding: Cystic Fibrosis Foundation
Studies to improve the cystic fibrosis newborn screening parental notification process. These studies will measure family preferences to tailor the delivery of educational material at the time of newborn screening CF diagnosis, and assess parental understanding and satisfaction of the notification process. Funding: Cystic Fibrosis Foundation
Antonia Popova, M.D.
The focus of my research is pulmonary complications of premature birth. These complications include bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurely-born infants in which lung alveoli fail to form normally, and asthma. My work combines animal experiments and an ex vivo lung model and, for selected studies human subject research.
My current research aims to understand the contribution of innate immune mechanisms to asthma development in prematurely born infants, especially those with BPD. Particularly, I am studying how early-life exposures associated with premature birth, such as exposure to oxygen and bacterial endotoxins, prime the innate immune system, causing exaggerated inflammatory responses to respiratory viral infection. Using an animal model, we found that damage associated molecular patterns, or DAMPs, activate Clec9a+CD103+ dendritic cells, thereby enhancing T cell responses to rhinovirus infection. We have also found evidence of DAMP signaling in tracheal aspirates from human preterm infants. Funding: NIH K23 HL109149