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Department of Pediatrics Heersink School of Medicine

Pediatric Pulmonology Research

Ongoing and Current Research

Ammar Saadoon Alishlash, M.D.
Dr. Saadoon Alishlash’s research focuses on studying the factors that affect lung development in children especially vitamin D deficiency. His laboratory also investigates the pulmonary vascular structure and function which include pulmonary complications of Sickle Cell disease, and pediatric pulmonary hypertension.

Tom Harris, M.D.
Dr. Harris' laboratory focuses on mechanisms that underlie cystic fibrosis (CF) lung disease, with the long-term goal of developing innovative approaches to therapy.  Pursuing the role of TGF-β as a genetic modifier of CF disease severity, I have developed 3 parallel and interconnected streams of research pursuit: 1) Myofibroblast activation and lung remodeling in CF 2) miRNA manipulation to augment F508del CFTR correction and 3) Consequence of smoke exposure on CF respiratory decline and response to therapy.  I am also interested in clinical strategies to improve CF outcomes including pharmaceutical studies, novel strategies for disease detection, and improving adherence with current therapeutic options.

Gabriela Oates, Ph.D.
Dr. Oates is a medical sociologist with a focus on social determinants of health and health disparities in chronic respiratory diseases. She investigates health-related behaviors in a social context, with the aim of developing interventions that improve respiratory health outcomes. Her work has documented the role of social determinants – financial resources, educational attainment, living conditions, family environment, and social support – for respiratory health and has demonstrated that these factors impact lung health from the very beginning of one’s life. Dr. Oates reports on geographic disparity in preventable chronic diseases and health-related behaviors by income, education, race, and gender, as well as racial and gender disparities in the incidence of lung and bronchus cancer. By geocoding clinical data to obtain neighborhood-level socio-environmental measures, she showed that socioeconomic disadvantage is associated with decreased adherence to pulmonary rehabilitation in chronic obstructive pulmonary disease. She also found that household income, mother’s education, and number of adult caregivers impact adherence to airway clearance therapy in pediatric cystic fibrosis. Finally, Dr. Oates has conducted studies that clarify the contributions of race, socioeconomic status, and perceived discrimination for health outcomes, showing that risk factors for systemic inflammation differ by race, gender, and indicators of socioeconomic status.

Isabel Virella-Lowell, M.D.
Dr. Lowell’s research centers on clinical trials in cystic fibrosis and asthma that look at new potential therapies or strategies for improving overall care.  She is also involved in a number of quality improvement studies in asthma, cystic fibrosis and hospital patient safety.

Faculty Research Interests

Ammar Saadoon Alishlash, M.D.
Dr. Saadoon Alishlash overlooks the research of pediatric pulmonary vascular disease and developmental aspects of the lung in children. He also has multiple publications about pediatric asthma, exhaled nitric oxide, cystic fibrosis microbiome, Flexible Bronchoscopy and pneumomediastinum in children.

Dr. Saadoon Alishlash's lab is located at Volker Hall building, Room 641

Jennifer Guimbellot, M.D.
Cystic Fibrosis, pharmacology, pharmacogenetics, in vitro biomarkers, personalized medicine

Tom Harris, M.D.
Dr. Harris investigates TGF-β associated pathobiology in cystic fibrosis (CF), with a long-term goal of developing innovative approaches to therapy. TGF-β is a genetic modifier of CF severity, providing mechanistic clues to disease progression.  He has identified increased levels of TGF-β in plasma, bronchoalveolar lavage fluid, and lung tissue to be associated with CF lung disease severity.  He has also identified TGF-β signaling as increased in CF lungs with TGF-β dependent myofibrobablasts mediating small airway remodeling in the disease. Additionally, he has served as site PI on several clinical trials investigating the CFTR modulators ivacaftor and lumacaftor.  Recently, he has pursued the mechanisms by which TGF-β suppresses CFTR synthesis and function in airway epithelia and nullifies the F508del CFTR response to lumacaftor correction.  He has now identified miRNA-145 as the mediator of TGF-β inhibition of CFTR, with restoration of F508del CFTR correction after miR-145 inhibition. miRNA are small (~22 base pair) non-coding RNA that destabilize mRNA transcripts and inhibit protein translation. In addition to these basic science pursuits, Dr. Harris is interested in the consequence of socioenvironmental determinants of health.  He specifically investigates the consequences of smoke exposure, poverty, and low paternal education on lung function, with an evolving focus of smoke exposure on CFTR modulator response.

Dr. Harris’ basic science laboratory is in Volker Hall

Wynton Hoover, M.D.
Clinical research related to Cystic Fibrosis involving early detection and treatment of lung disease, prevention and eradication of pseudomonas prior to chronic colonization and treatment of difficult infections such as MRSA.

Gabriela Oates, Ph.D.

  • Social determinants of health, psychosocial stress, and outcomes research

  • Adherence and self-management, with a focus on chronic respiratory conditions

Dr. Oates’s work places biological and behavioral processes in a social context to understand the mechanisms through which the social and physical environments impact health behaviors and health outcomes. Her research investigates the impact of individual- and neighborhood-level social determinants on adherence and outcomes in chronic respiratory conditions. The goal of this work is to develop strategies for reducing the burden of socioeconomic disparities on lung health.

Isabel Virella-Lowell, M.D.
Asthma therapies, Adherence, Cystic Fibrosis Therapies, Airway Inflammation, optimizing the conduction of clinical trials and delivery of inpatient and outpatient care.

Basic Science Research

Ammar Saadoon Alishlash, M.D.
Dr. Saadoon Alishlash’s lab utilizes animal models of pulmonary hypertension and acute chest syndrome in Sickle Cell Disease to study the pathophysiology and management of those complications. He also uses vitamin D deficiency mouse model to investigate the effect of vitamin D on the lung and pulmonary vascular development.

Jennifer Guimbellot, M.D.
The Guimbellot laboratory is focused on developing personalized strategies to optimize drug therapy for patients with cystic fibrosis and related diseases. In vitro models are being evaluated as screening methods to assess efficacy of small molecule therapies from individual patients ex vivo, which will provide unique and innovative tools to predict corrector activity in any candidate for CFTR modulators. In addition, we have initiated a comprehensive research program to incorporate pharmacometrics and pharmacogenomics into development and validation of these models, as well as to understand tissue-specific metabolism of this new class of drugs on personalized efficacy.

Tom Harris, M.D.
TGF-beta pathobiology in CF lung disease:  TGF-beta is the most established genetic modifier of CF lung disease.  Dr. Harris pursues the mechanisms by which TGF-beta modifies respiratory trajectory in CF, with a focus on airway remodeling and miRNA.

Airway remodeling in CF:  Dr. Harris has identified the role of activated pro-fibrotic fibroblasts called myofibroblasts to airway remodeling in CF.  These TGF-beta dependent fibroblast develop in response to epithelial injury and mechanical strain as part of the regenerative process.  If these stimuli do not resolve, myofibroblasts then produce increased extracellular matrices that result in small airway and parenchymal remodeling.  Dr. Harris has identified the contribution of constrictive bronchiolitis to loss of small airway patency and extensive parenchymal fibrosis in CF lung disease.  These findings indicate potential of nuanced anti-fibrotic or anti-TGF-beta therapies to ameliorated disease progression refractory to current therapy.  These studies on remodeling in CF formed the basis of his CFF Shwachman Clinical Investigator Award.

miRNA in CF:  Dr. Harris has identified the role of miRNA (small, ~22bp, non-coding nucleotide sequences) to modify CFTR synthesis and function.  miRNA bind to the 3’-untranslated region (3’-UTR) of CFTR mRNA to decrease transcript stability and protein translation.  Dr. Harris has identified miR-145 as the mediator of TGF-beta suppression of CFTR and miR-145 as an inhibitor of F508del CFTR correction.  Antagonism to miR-145 eliminates TGF-beta suppression of CFTR and augments lumacaftor/ivacaftor correction of mutant CFTR.  These studies formed the basis for his NIH NHLBI K08 Career Development Award.

Clinical Research

Ammar Saadoon Alishlash, M.D.
In collaborates with the Hematology-Oncology division, Dr. Saadoon Alishlash investigates contributing factors and management of Sickle Cell Disease pulmonary complications including four categories: Acute Chest Syndrome, Pulmonary Hypertension, Asthma and Sleep Disordered breathing.  

Tom Harris, M.D.
In addition to his basic science work, Dr. Harris serves as site PI for multiple Phase III CFTR modulator studies.  Currently, he evaluates ivacaftor in toddlers aged 0-2, lumacaftor/ivacaftor for toddlers aged 12-24 months.  He also investigates next-generation therapy with tezacaftor/ivacaftor for age 6-11.  Previous work on ivacaftor for age 2-5 and lumacaftor/ivacaftor for age 6-11 led to FDA clinical approval for the CF population. 

Isabel Virella-Lowell, M.D.

  1. Vertex Pharmaceuticals Incorporated. A Phase 3, 2-Part, Open-label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have a CFTR Gating Mutation. Principal Investigator

  2. Proteostasis, A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect of PTI-428 in Subjects with Cystic Fibrosis, Principal Investigator

  3. Cystic Fibrosis Foundation Therapeutics, Prospective Evaluation of a Standardized Approach to Diagnosis (PREDICT) and Treatment (PATIENCE) of Nontuberculous Mycobacteria Disease in Cystic Fibrosis, Co—Investigator

  4. Proteostasis, A Multi-Center, Randomized, Placebo-Controlled, Phase 1, Two-Part Study Designed to Assess the Safety, Tolerability, Pharmacokinetics, Food Effect, and Drug-Drug Interactions of PTI-801 in Healthy Volunteers, and Safety, Tolerability, and Pharmacokinetics of PTI-801 in Subjects with Cystic Fibrosis, Sub-Investigator

  5. Cystic Fibrosis Foundation Therapeutics, The CHEC-SC Cohort Study: Characterizing CFTR Modulated Changes in Sweat Chloride and their Association with Clinical Outcomes (the CHEC-SC study), Sub-Investigator

  6. Cystic Fibrosis Foundation Therapeutics. Standardized Treatment of Pulmonary Exacerbations II, Sub-Investigator

  7. Vertex Pharmaceuticals Incorporated, A Study Evaluating the Long Term Safety and Efficacy of VX-659 Combination Therapy, Sub-Investigator

  8. Vertex Pharmaceuticals Incorporated. A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis, Sub-Investigator

  9. Vertex Pharmaceuticals Incorporated. A Phase 3b, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Safety, Efficacy, and Tolerability of Tezacaftor/Ivacaftor (TEZ/IVA) in an Orkambi-experienced Population Who Are Homozygous for the F508del-CFTR Mutation, Sub-Investigator

  10. Vertex Pharmaceuticals Incorporated. A Phase 3, 2-Arm, Open-label Study to Evaluate the Safety and Pharmacodynamics of Long-term Ivacaftor Treatment in Subjects with Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have a CFTR Gating Mutation, Sub-Investigator

  11. Vertex Pharmaceuticals Incorporated. A Phase 3, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment with Lumacaftor in Combination with Ivacaftor in Subjects Aged 6 Years and Older with Cystic Fibrosis, Homozygous for the F508del-CFTR Sub-Investigator

  12. Vertex Pharmaceuticals Incorporated. A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With VX-661 in Combination with Ivacaftor in Subjects Aged 12 Years and Older with Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation. Sub-Investigator

Quality Improvement Research

Ammar Saadoon Alishlash, M.D.
Dr. Saadoon Alishlash established the Acute Chest Syndrome protocol to improve the outcomes of Sickle Cell Disease patients admitted with acute chest syndrome.

Tom Harris, M.D.
Dr. Harris also investigates the consequence of socioeconomic determinants of health in CF disease, with a focus of the consequence in childhood.  This has led to the identification of paternal education as a risk factor for detriments in lung function and the consequence of second-hand smoke exposure on CF pulmonary decline. 

Isabel Virella-Lowell, M.D.

2017– 2018: Alabama Child Health Improvement Alliance “Breathe Easy” project  

2017-present: Improving adherence and medicine reconciliation in asthma clinic. 

2015-present: Improving the rate at which we administer Asthma Control Tests (ACT), Asthma Action Plans (AAP) and flu shots amongst asthmatics seen in Pediatric Pulmonology clinic. 

2015-present: Implementation of the Depression and Anxiety Guidelines in Cystic Fibrosis. Developed a structured plan for expanding screen in CF clinic and provided patients with option to obtain e-therapy given obstacles to obtaining good mental health care in smaller rural areas or cities far from Birmingham

Publications