Division of Pulmonary Medicine | Research Activities

Fellows in Pediatric Pulmonology pursue a research project during the second and third years of their training. This project can involve clinical, translational, basic science, or educational research. Selection of a project is guided by consultation with the Fellowship Director, the Division Chief, and other members of the Division. The goal is to have fellows choose an area of research that interests them and also provides strong mentorship.

General Research Activities

The BCH Division of Pulmonary Medicine is actively engaged in a wide range of basic, translational, clinical and educational research initiatives developed to advance our understanding of pediatric lung disease that will ultimately lead to new diagnostic and therapeutic strategies for our patients. Supported by more than $9.8 million in awarded research funds this past year, the Division has published 98 peer-reviewed manuscripts in a wide range of academic journals, including Pediatrics, the American Journal of Respiratory and Critical Care Medicine, Cell Stem Cell, Lancet Respiratory Medicine, the Journal of Allergy and Clinical Immunology, the Journal of Cystic Fibrosis, and many others.

The Division’s laboratories occupy 6,650 square feet of space on the 4th floor of the John Enders Research Building of Boston Children’s Hospital. The division labs also house six NIH-supported pulmonary investigators. As members of Boston Children’s Hospital and Harvard Medical School, our fellows have access to all our institutions’ core facilities, including a state-of-the-art animal facility, a Cell Imaging and Phenotyping Core (with access to two confocal microscopes, multichannel flow cytometers, and other imaging and cell sorting platforms), and a transgenic animal core. To make research more accessible to our fellows and all our faculty, the Division has in place multiple resources to assist with study organization and grant development including a dedicated grants administrator, a Translational Research Operations Manager, a Clinical Research Manager overseeing clinical trials, a biostatistician, a bioinformatics and data management team, and a number of Research Assistants and Research Coordinators.

Our Division is a world-leader in conducting clinical trials in pediatric populations. This is possible due to the extraordinary work of our Clinical Trials Group, Directed by Dr. Jonathan Gaffin. Staffed by our Clinical Research Coordinator and Clinical Research Nursing Managers and research personel, this team conducts at any given time between 15 and 30 clinical trials, including studies in CF, Childhood Interstitial Lung Disease, Asthma, Primary Ciliary Dyskinesia, Pulmonary Artery Hypertension, and Bronchopulmonary Dysplasia.

Collaborative research arrangements within the Harvard Medical area are extensive and include the Divisions of Newborn Medicine, Immunology, Allergy, Gastroenterology, Informatics, and others within Boston Children’s Hospital; the Respiratory Division of Brigham & Women’s Hospital; the Physiology Department of the Harvard School of Public Health; Harvard Medical School and the Channing Laboratories at Brigham and Women’s Hospital. The research progress of the fellow is monitored and facilitated through biannual presentations before the fellow’s Scholarship Oversight Committee.

Grant awards:

The Division of Pulmonary Medicine is highly competitive for grant external support, with numerous successful applications this year to the National Institutes of Health (NIH), the American Thoracic Society (ATS), the Cystic Fibrosis Foundation (CFF), and the National Organization for Rare Diseases (NORD), among others.

Recent Pulmonary Fellow grant awards:

Gabriel Paris: 1st and 2nd year Fellowship Award (CF Foundation)

Chandra Swanson: 2nd year Fellowship Award (CF Foundation)

Bob Sun: Pediatric Scientist Development Program Award

Taylor Baumann: BWH/BCH T32 Research Fellowship (NHLBI)

Taylor Baumann: 1st and 2nd year Fellowship Award (CF Foundation)

Kristen Richard: 1st and 2nd Year Fellowship Award (CF Foundation)

Kristen Richard: BCH Academy Health Professionals Education Innovation

Julia Lee: BCH Alumni Association Academic Development Award

Po-Yang Tsou: ATS ASPIRE (Academic Sleep Pulmonary Integrated Research/Clinical) Fellowship Program (ATS)

Stuart Rollins: 3rd and 4th year Fellowship Award (CF Foundation)

Dorothy Curran: 1st and 2nd year Fellowship Award (CF Foundation)

Jaclyn Davis: 1st year Fellowship Award; 2nd Year Fellowship Award, 3rd year Fellowship Award, 4th year Fellowship Award (CF Foundation)

Tim Klouda: BWH/BCH T32 Research Fellowship (NHLBI)

Faculty grant awards (2023-2024)

Pyong Park: Glypicans in Bacterial Lung Infection (NIH)

Greg Sawicki: Cystic Fibrosis Learning Network (CFF)

Ahmet Uluer: Cystic Fibrosis Learning Network- Adult Program (CFF)

Yunhye Kim: Deficiency of Smooth Muscle ADAR1 Exacerbates Vascular Remodeling and Pulmonary Hypertension (AHA)

Ryan Perkins: TDN SHARING Working Subgroup: Junior Investigator Member (CFF)

Suzanne Dahlberg: Translating AI Lung Cancer Risk Models into the Clinic (OTHER)

Benji Raby: Molecular understanding of the GSDMB-regulated innate immune response (NIH)

Benji Raby: Integrative Genomics of Childhood Interstitial Lung Disease (NIH)

Tim Klouda: Mural Cells Contribution to Vascular Remodeling in Flow Induced Pulmonary Hypertension (NIH)

Greg Sawicki: 2023 Leadership and Design Grant (RAMP) (CFF)

Stuart Rollins: Integrated Training in Respiratory Research (NIH)

Seyni Gueye-Ndiaye: Variation of Cerebral and Peripheral Oxygenation in Children with Sleep Disordered Breathing (BCH)

Ryan Perkins: Assessing Health Insurance Choice and the Impact on Outcomes in Cystic Fibrosis (CFF)

Laura Chiel: Experiences of learners and program director participants in novel learner education handover from pediatric residency to subspecialty fellowship (OTHER)

Carolyn Snell: 2024 Success with Therapies Research Consortium (STRC) Award (CFF)

Ahmet Uluer: Cystic Fibrosis Foundation Therapeutics Development (TDC) (CFF)

Manuela Cernadas: Health Outcomes of Parents with Cystic Fibrosis (CFF)

Greg Sawicki: Co-Chair of the Success with Therapies Research Consortium (CFF)

Current Research Programs

Pulmonary Genetics Program-
Dr. Raby is a pulmonologist and a genetic epidemiologist known internationally as an expert on the genetics and genomics of asthma, rare lung disease, and as a leader in the integration of genetic diagnostics in the clinical practice of pulmonary medicine. He leads an active NIH-funded laboratory that combines population-based integrative genomics with functional genetics to define the molecular determinants of asthma. He has been continuously NIH funded for nearly two decades and his laboratory is currently supported by four NIH R01 awards focused on using population genetic and genomic approaches in the study of asthma and Interstitial Lung Disease (ILD). Dr. Raby has published more than 220 original science manuscripts on these topics, including telomere biology, telomeropathy, and ILD. Most recently, Dr. Raby’s group has published new findings demonstrating the importance of activation of the TREM-1 signaling pathway in poorly controlled and severe asthma (now the most replicated gene expression signature of poor asthma control) and the value of screening at-risk relatives of patients with ILD for pre-clinical evidence of ILD. Current projects are focused on understanding the functional mechanisms by which asthma variants confer disease, single-cell RNA-sequencing and biomarker studies in poor asthma control, gene mapping of rare childhood lung disease, and the development of novel computational approaches for the study of complex genetic disorders. Dr. Raby has led numerous large multi-institutional projects exhibiting his prowess in the analysis of complex molecular data. He has conducted integrative genomic analyses of thousands of subjects and developed network-based data analysis approaches for novel gene discovery.

Extracellular Matrix Biology in Lung Health and Disease- Dr. Pyong Park
Dr. Pyong Park is an authority on the proteoglycans – extracellular matrix components that regulate receptor-ligand interactions, cellular communication, and tissue remodeling in health and disease. Most recently, his lab discovered that syndecans regulate the anti-inflammatory activity of mesenchymal stem cells (MSCs) in acute lung injury and that glypicans modulate the pathogenesis of pneumonia. His team is currently pursuing the molecular and cellular mechanisms of how syndecans and glypicans function in these manners.

Pluripotent Stem Cells- Dr. Ruby Wang
Dr. Ruobing Wang is developing approaches to use induced pluripotent stem cells (iPSC) and CRISPR-cas9 gene-editing tools to model Cystic Fibrosis (CF). Using samples obtained from CF patients with extreme phenotypes of lung function decline, Dr. Wang has derived 19 viable iPSC lines, has CRISPR-corrected the mutant CFTR gene in 5, and has successfully helped to develop a cell-based model based on in vitro differentiation of patient derived iPSCs to 1) airway epithelium both as 3D-organoids and 2D pseudostratified epithelium plated on air-liquid interface, and 2) functional putative macrophages. The iPSC-airway epithelium grown as 2D pseudostratified layer on air-liquid interface is capable of tight junction barrier formation, and mucociliary differentiation, and generates both the major airway cell types, as well as the rare cell types, including pulmonary ionocytes. She has shown that this platform is useful to model cystic fibrosis by demonstrating restoration of Cl- activities in CF iPSC after correction of CFTR via Ussing chamber assay. Recently, she has been using this platform to study CFTR-deficient epithelial response to SARS-CoV-2 and other CF relevant pathogens.

Computational Biology- Dr. Sung Chun
Dr. Sung Chun is a geneticist and computational biologist with an interest in complex trait genetics. He has developed approaches for co-localization of clinical phenotype and regulatory genetic (eQTL) associations and for using polygenic risk scores in the study of pulmonary disease. Current projects include applying these approaches in a clinical setting to improve risk stratification among at-risk relatives of patients with ILD, rare variant mapping in childhood interstitial lung disease, and genome-wide association studies in Eosinophilic Granulomatosis and Polyangiitis (EGPA, formerly called Churg-Strauss Syndrome). Dr. Chun and his team provide bioinformatic and statistical support to fellows and faculty across the division.

Pulmonary Vascular Disease- Dr. Ke Yuan
Dr. Ke Yuan is a vascular biologist whose research focuses on the role of lung pericytes in the muscularization of pulmonary arterioles in response to chronic hypoxia and the development of pulmonary arterial hypertension (PAH). The major pathological hallmark of PAH is the uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs), leading to the progressive occlusion of precapillary pulmonary arteries. Through the use of lineage tracing and fate mapping animal models, Dr. Yuan has published foundational studies demonstrating that pericytes can transdifferentiate into smooth muscle-like cells, contributing to abnormal muscularization and vascular obstruction. Her research employs cutting-edge technologies, including single-cell RNA sequencing, spatial transcriptomics, tissue clearing, 3D deep tissue light-sheet imaging, and super-resolution microscopy, to study changes in lung vasculature. Additionally, her group has optimized methods to differentiate pericytes from other mural cells in both mouse and human samples. Dr. Yuan’s laboratory consistently contributes to a deeper and clinically relevant understanding of pericyte biology, paving the way for novel therapeutic strategies in PAH.

Clinical Trials Program-
Our pulmonary clinical research team remains among the most active clinical trials group in the country, continuing to enroll large numbers of subjects across a diverse set of clinical trials. We serve the Northeastern U.S. and all of New England as a major referral center for clinical trials in pulmonary disease, both for pediatrics and adults. We have participated in pivotal clinical trials for cystic fibrosis and continue to perform clinical trials in CFTR-modulating agents, anti-inflammatory and anti-bacterial drugs, as well as novel gene therapies for CF. The outcomes of these trials have had major impact on the health and quality of life of the majority of patients with CF. We continue to participate in clinical trials to treat asthma, interstitial lung disease, ciliary dyskinesia, and RSV. Our research portfolio also includes many cutting edge research projects led by our own Pulmonary Division clinician-scientists, including gene mapping efforts in Childhood Interstitial Lung Disease (Drs. Alicia Casey and Martha Fishman); several initiatives in the areas of Bronchopulmonary Dysplasia (BPD) and asthma (Drs. Lystra Hayden, Catherine Sheils, and Jonathan Gaffin), sleep disordered breathing syndromes (Drs. Katwa, Rosen, Gueye-Ndiaye); severe respiratory infections due to viral illness, and genetics/genomics of rare lung diseases (Dr. Raby).The clinical trials program provides personnel, informatics, and regulatory oversight to facilitate patient enrollment, sample collection and processing, and data management.

Childhood Interstitial Lung Disease (ChILD) Research-
Through the Pulmonary Biobank and BCH Sequencing Cohort Initiatives, the ChILD team utilizes a pipeline for whole exome (and in some whole genome) sequencing analysis to evaluate undiagnosed cases and continue to grow a local patient registry to facilitate translational research. This collaboration has led to the identification of mutations in multiple known and novel genes in cases of unexplained diffuse lung disease. Success in these efforts formed the basis of our divisions Chan-Zuckerberg Initiative funded project to create a single nuclear and spatial transcriptomic Atlas for the chILD community around the globe. Our ChILD program has also conducted multiple clinical and genotype phenotype correlation clinical research studies in ILD. BCH is a major contributor of patients to the national chILD registry – a multicenter collaborative developed to accelerate scientific investigation and clinical trials research of these understudied diseases.

Bronchopulmonary Dysplasia Research-
Our BPD group has numerous active clinical, data science, and basic science research projects in bronchopulmonary dysplasia. Dr. Gaffin’s ongoing research examines the environmental determinants of impaired lung function and respiratory health in children. He currently has support from the NIH/NIEHS to assess the impact of indoor air quality on respiratory outcomes in children with BPD. Dr. Hayden is the PI of the Preterm Lung Patient Registry and Biobank, which follows longitudinal outcomes among over 1,300 patients in BPD clinic. Studies in this cohort led by Dr. Levin, a dual trained neonatologist and pulmonologist with expertise in clinical informatics, have demonstrated worsening obstructive lung function pattern with age, revealing that former premature infants are at risk for ongoing abnormal pulmonary development in childhood. Dr. Sheils has led the BCH arm of the multi-center implementation protocol of home oximetry, which will improve and revolutionize home monitoring of patients with BPD. BCH is also an active participant in the BPD collaborative, a multi-national group of centers dedicated to improving outcomes in children with BPD. This has included numerous multi-center epidemiological analyses evaluating medical, environmental, and socioeconomic ​impacts on the health outcomes of children with BPD, as well as outcomes in ventilator dependent children with BPD.  There are also basic science research opportunities with collaborators in neonatology (Dr Kourembanas), whose laboratory focuses on the biology and application of mesenchymal stem cell extracellular vesicles/exosomes in the immune pathways that lead to BPD. Fellows have been actively involved in all these efforts and the BPD team welcomes future fellow-initiated investigations.

Sleep-disordered Breathing Research-
Our sleep faculty have made several noteworthy advances this past year. Dr. Umakanth Katwa published an algorithm for management of infants with Pierre Robin sequence. Dr. Dennis Rosen completed a study that identified a much-higher prevalence of periodic limb-movements of sleep in children with Down syndrome than in typical patients. This has resulted in the launching of a joint QI initiative with the Down syndrome program at BCH to improve the screening for and treatment of this condition in children with Down syndrome. This is expected to improve their overall health and to have a positive impact on their ability to integrate into mainstream educational frameworks. Dr. Eliot Katz published two studies on the evaluation and stratification of infants having brief resolved unexplained events.

Medical Education Research-
Fellows and faculty have conducted medical education research including related to curriculum design, feedback, and simulation. An example of a recent medical education-related fellowship project was conducting a needs assessment of the pediatric pulmonary fellowship curriculum, which was then used to inform specific teaching initiatives. One of our fellows recently surveyed pediatric pulmonary fellows across the country on the perceived effectiveness of virtual pulmonary fellowship interviews. Another one of our fellows was recently accepted into the Virtual Program for Post-Graduate Trainees: Future Academic Clinical Educators program. Opportunities for medical education related grant funding are available through the institution, with several recent fellows receiving these awards.