Research

Discovery Award Program

Program Goals

The main objective of the Discovery Award Program is to bring talented and accomplished basic and physician scientists together in an interdisciplinary manner promoting the generation of research that identifies viable targets for the treatment of various forms of lung disease. Teams of basic and physician scientists will propose research based on existing preliminary results that show promise. The competitive selection of projects will be conducted by an advisory board consisting of qualified outside and institutional scientists. Projects will be selected based upon the expertise of the team and the quality of preliminary data presented. The most feasible and highest quality proposals will be funded with the major goal of pushing forward translational research on pulmonary diseases. These proposals should be viewed as Pre-RO1 awards provided to help the investigative team generate findings that will lead to eventual high level extramural grant submissions. Success of this program will be measured by the quality of data generated and the securing of additional public or private funding to continue the research.

Measures of Success

Quality data generation
Publication in top journals
Successful grant applications
Patent filings

Oversight and Assessment

External Advisory Board
Center leadership
Yearly scientific retreat to assess progress and showcase findings

Discovery Award Winners: Research Summaries

  • Development of Patient-Specific Therapeutic Approaches for Cystic Fibrosis

    PI:  Brian R. Davis, PhD, Brown Foundation Institute of Molecular Medicine
    Co-PI:  Wa Xian, PhD, Brown Foundation Institute of Molecular Medicine
    Co-I:  Ricardo Mosquera, MD, Department of Pediatrics, UTHealth – McGovern Medical School

    Cystic Fibrosis (CF), a genetically inherited disease caused by DNA mutations in a specific gene named CFTR, results in recurrent infections and inflammation in the lung. This project is focused on performing a detailed characterization of a specific population of cells in the lungs of CF patients, namely the stem cells. What we wish to determine is whether the stem cells, which are responsible for the ongoing maintenance and regeneration of the lung airway, are adversely affected — either as a direct consequence of the CFTR mutation or as an indirect consequence of continuous exposure to inflammation and injury. In addition, we wish to assess whether precise genetic correction of the CFTR mutation in these cells restores the ability of CF stem cells to give rise to functional lung tissue. If this latter possibility is demonstrated, then this will potentially lead to new therapeutic approaches in which CF patient-specific lung stem cells are corrected—either directly in the CF patient or first corrected in a clinical laboratory and then transplanted back into the lungs of the same patient. The hope is that that the presence of genetically corrected lung stem cells would result in restoration of healthy lung tissue.

  • MicroRNA and mRNA Epigenetics as Post-transcriptional Regulators of Allergic Airway Inflammation

    PI:  Ann-Bin Shyu, PhD, Department of Biochemistry and Molecular Biology, UTHealth – McGovern Medical School
    Co-I:  Jeffrey T. Chang, PhD, Department of Integrative Biology & Pharmacology, UTHealth – McGovern Medical School
    Co-I:  Chyi-Ying A. Chen, PhD, Department of Biochemistry and Molecular Biology, UTHealth – McGovern Medical School
    Co-I:  Amber Luong, MD, PhD, Department of Otorhinolaryngology, UTHealth – McGovern Medical School

    Respiratory epithelial cells, lining the respiratory tract, can sense inhaled allergens, pollutants, proteases, and microbes and respond through cell surface receptors, thereby leading to activation of stress and inflammatory responses. One key signaling pathway that mediates these responses is called NF-κB signaling. We recently unraveled a novel cellular regulation by a micro-nucleic acid, termed microRNA 26 (miR-26). This small RNA dampens inflammatory responses in human bronchial epithelial cells by directly down-regulating NF-κB signaling. Our first research plan is to investigate the effects of miR-26 on NF-κB signaling pathway in inflammatory responses and tissue remodeling processes in airway epithelial cells. The second aspect of our research plan is to study the conceptually novel and largely unexplored relationship between airway inflammation and modifications of messenger RNA (mRNA). Human mRNAs contain many methylated adenosine (m6A) residues, which represents a previously unknown layer of regulation of gene expression. We will test whether patients with altered dynamics of m6A modification on messenger RNA may exhibit aberrant gene expression related to airway inflammation and tissue remodeling. Collectively, our studies have great potential to provide insight into novel therapeutic approaches for alleviation of airway inflammation associated with chronic airway diseases, such as chronic sinusitis, lung fibrosis, and asthma.

  • CFIm25 Links Alternative Polyadenylation with Pulmonary Hypertension and Right Ventricle Hypertrophy

    PI:  Harry Karmouty-Quintana, PhD, Assistant Professor, Department of Biochemistry and Molecular Biology, UTHealth – McGovern Medical School
    Co-I:  Bindu Akkanti, M.D., Assistant Professor, Division of Pulmonary, Critical Care and Sleep Medicine, UTHealth – McGovern Medical School
    Co-I:  Leng Han, Ph.D., Assistant Professor, Department of Biochemistry and Molecular Biology, UTHealth – McGovern Medical School
    Co-I:  Keith Adam Youker, Ph.D., Assistant Research Professor, Houston Methodist Hospital Research Institute

    The appearance of high blood pressure in the lungs, termed pulmonary hypertension (PH), is the one of the deadliest complication that affects many patients already suffering from chronic lung diseases such as chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). Sadly, the mechanisms that lead to this deadly complication are not entirely understood and as a result there are no treatment options other than lung transplantation for patients with PH. PH is fatal because the wall of the arteries that carry blood in the lung thicken and eventually block the flow of blood, resulting in increased blood pressure in the lungs. This higher blood pressure means that the heart has to work harder to pump blood to the lungs causing the walls of the heart to also thicken and eventually fail; causing many patients die from right-heart failure. A new discovery of my lab is that a protein called CFIm25 appears to control the level of many molecules that regulate wall thickness. We believe that when CFIm25 levels are reduced more molecules that make the wall thicker are produced. As a result our research efforts focus on preventing CFIm25 to go down in disease, as a new way to treat both PH and prevent heart attacks.

  • Induced Pluripotent Stem (iPS) Cell-Derived Lung Progenitor Cells as Therapy for Lung Injury and Surfactant Protein Disorders

    PI:  Rick A. Wetsel, PhD, Brown Foundation Institute of Molecular Medicine
    Co-I:  Matthew T. Harting, MD, Pediatric Surgery, UTHealth – McGovern Medical School
    Co-I:  Brian R. Davis, PhD, Brown Foundation Institute of Molecular Medicine
    Co-I:  Dachun Wang, MD, Brown Foundation Institute of Molecular Medicine

    Respiratory diseases are a leading cause of mortality and morbidity worldwide, and are a major cause of death in babies less than 1 year of age. In the United States alone, 35 million Americans suffer with lung disease, accounting for approximately 400,000 deaths per year. Current treatments for lung disease at best provide symptomatic relief but offer no prospect of cure or disease reversal.  Lung transplantation is the often the only viable option.  Our research team is focused on developing novel cell based therapeutics to treat patients suffering from lung injury and from infants affected by genetically inherited diseases affecting normal lung function.  Our overall approach will test the use of patient specific induced pluripotent stem cells (iPSCs).  These iPSCs are derived from a small skin biopsy and can be differentiated into pure populations of lung cells that can be transplanted into the lungs of patients for repair of damaged pulmonary tissue caused by acute or chronic lung diseases, such as COPD.  After genetic correction, they also can be used for gene therapy for patients with genetic disorders affecting normal lung function. Since these transplanted cells are derived from the patient undergoing therapy, there will be no graft rejection issues—thereby avoiding a major complication of lung transplantation.

  • Metabolomic Profiling Reveals New Insight, Sensitive Biomarkers and Innovative Approaches for Pulmonary Hypertension

    PI:  Yang Xia, MD, PhD, Professor, Department of Biochemistry and Molecular Biology, UTHealth – McGovern Medical School
    Co-I:  Harinder S. Juneja, MD, Professor and Director, Division of Hematology, Department of Internal Medicine, UTHealth – McGovern Medical School
    Co-I:  Aravind Yadav, MD, Assistant Professor, Pulmonary Medicine, Department of Pediatrics, UTHealth – McGovern Medical School
    Co-I:  Harry Karmouty-Quintana, PhD, Assistant Professor, Department of Biochemistry and Molecular Biology, UTHealth – McGovern Medical School

    Pulmonary hypertension (PH) is a dangerous condition with high morbidity and mortality due to lack of early pre-symptomatic tests and effective therapies. Insufficient oxygen (hypoxia) is one of the major initial triggers promoting PH.  Sickle cell disease (SCD) is a devastating genetic hemolytic disorder constantly facing hypoxia and is associated with PH. The proposed research builds on the results of our unbiased high throughput metabolomic screen revealing that adenosine (Ado), sphingosine 1 phosphate (S1P) and 2,3-bisphosphoglycerate (2,3-BPG) are metabolites elevated in the blood of humans and mice with SCD and in healthy individuals adapting to high altitude hypoxia.  Further studies showed that these metabolites collaboratively work together facilitating O2 release from hemoglobin to prevent hypoxemia and progression to PH. However, this process is detrimental for SCD patients by promoting O2 release, sickling and development of PH. Taken together, our innovative metabolomic screening revealed multiple common hypoxic responsive metabolites and opens up novel promising therapeutic approaches for the treatment of PH. Thus, the major goal of our proposed research is to determine whether our newly identified hypoxia-responsive circulating and erythrocyte metabolites are sensitive biomarkers for early prediction of PH in SCD patients and important therapeutic targets in pathogenesis of PH in non-SCD settings.