2007 ATS Research Grant Recipients

Partnership Grants:

ATS/Asthma and Allergy Foundation of America Partnership Grant in Asthma

• Co-funded by the ATS and the Asthma and Allergy Foundation of America

Loren C. Denlinger, MD, PhD

University of Wisconsin, School of Medicine and Public Health
Research: “Regulation of Nucleotide Receptor Function During Infection in Asthma”

Asthma affects seven percent of the US population. Recent data suggest that up to half of the patients who remain symptomatic despite standard therapy may have chronic airway infection by viruses and/or atypical bacteria such as Chlamydia pneumoniae.  Dr. Denlinger plans to study cells taken from the airways of patients with asthma as well as healthy volunteers.  Specific experiments will dissect the contributions from the patient’s immune system, asthma medications and infection by Chlamydia in a culture dish on the ability of these cells to regulate their own life span. Others have shown that these cells from patients with asthma have decreased life spans under certain conditions, causing gaps to form in this defensive barrier.

ATS/Coalition for Pulmonary Fibrosis Partnership Grant in Pulmonary Fibrosis

• Co-funded by the ATS and the Coalition for Pulmonary Fibrosis

Sonye K. Danoff, MD, PhD

Johns Hopkins University
Research: “VEGF: Marker or Mediator of Lung Injury in Pulmonary Fibrosis?”

Pulmonary fibrosis results in progressive, irreversible scarring of the lungs.  Although it occurs most often in people in their sixties and seventies, it can also occur in younger people.  Among younger people with pulmonary fibrosis, the cause of the lung problem is frequently an autoimmune disorder.  Dr. Danoff proposes to determine how a signal (vascular endothelial growth factor) that is present in normal lungs might also be involved in the lung injury which results in fibrosis.  Understanding this will help to explain how all types of lung fibrosis might occur.  This is particularly promising since medicines which block this pathway already exist and are being tested in patients with other diseases.  Therefore, these medicines might be quickly available for treating pulmonary fibrosis.

ATS/COPD Foundation Partnership Grant in COPD

• Co-funded by the ATS and the COPD Foundation

Brigitte N. Gomperts, MD

University of California, Los Angeles
Research: “Circulating Stem/Progenitor Epithelial Cells in Airway Repair”

The discovery of stem cells that have the ability to form new lung cells has created much excitement about the potential use of stem cells for therapy.  However, there is still much to be learned about these stem cells.  It has been shown that airway repair after injury is derived from resident airway stem cells and from blood borne stem cells.  Preventing the contribution of blood borne stem cells to airway repair resulted in similar abnormalities in the airway to those seen in patients with chronic obstructive pulmonary disease (COPD).  Dr. Gomperts, therefore, plans to study the resident and blood borne lung stem cell populations in COPD.

ATS/Foundation for Sarcoidosis Research Partnership Grant in Sarcoidosis

• Co-funded by the ATS and the Foundation for Sarcoidosis Research

Michael T. Falta, PhD

University of Colorado Denver Health Sciences Center
Research: “T Cell Ligands in Sarcoidosis”

Sarcoidosis is an immune disease that mainly involves the lungs, but any organ of the body can be affected.  It is not known what causes this disease; however, one type of immune blood cell, called T lymphocytes, may be important in the development of inflammation.  T cells and other cell types become overactive, and their activity results in the formation of lumps of inflamed tissue called granulomas that can appear all over the body.  The purpose of Dr. Falta’s research is to find out how T cells become overactivated in sarcoidosis patients and to understand how these cells are involved in granuloma formation.  This information might lead to an understanding of what causes disease and suggest new therapies for treating sarcoidosis.

ATS/Hermansky-Pudlak Syndrome Network Partnership Grant in Hermansky-Pudlak Syndrome

• Co-funded by the ATS and the Hermansky-Pudlak Syndrome Network

Lisa R. Young, MD

2007 Carl Booberg Research Awardee
Cincinnati Children’s Hospital Medical Center
Research: “Alveolar Cell Dysfunction in Pulmonary Fibrosis”

Interstitial lung diseases (ILD) are disorders which cause progressive shortness of breath and respiratory compromise due to scarring (fibrosis) in the lung. The causes of ILD are largely unknown, and no effective treatments exist for most diseases.  Hermansky- Pudlak Syndrome (HPS) is a rare inherited disorder in which almost all affected adults develop pulmonary fibrosis. This proposal will use a powerful genetic mouse model to understand how scarring occurs in the lung.  Insights gained from this study may lead to novel approaches to the treatment of ILD.

ATS/LUNGevity Foundation Partnership Grants in Lung Cancer

• Co-funded by the ATS and the LUNGevity Foundation

ShouWei Han, MD, PhD

Emory University
Research: “Signaling through PPARy in Lung Cancer: Potential Therapeutic Role of PPARy Ligands”

Lung cancer is currently the leading cause of cancer death in men and women in the US.  Despite recent advances in understanding the molecular biology of lung cancer and despite the introduction of new therapies for its treatment, less than 15 percent of lung cancer patients survive more than 5 years.  The lack of advancement in this area is related to our limited knowledge about factors that are able to promote cancer formation in the lung, able to stimulate cancer cell growth and able to render cancer cells resistant to chemotherapy.  Dr. Han’s project seeks to investigate the mechanisms that control non-small cell lung carcinoma cell growth and also to explore the effects of novel anti-cancer therapies.

Kostyantyn Krysan, PhD

University of California, Los Angeles
Research: “Modulation of PGE2-Dependent EGFR Inhibitor Resistance in NSCLC by E-Cadherin”

Lung cancer, which accounts for more than 28 percent of all cancer deaths each year, is the leading cause of cancer related mortality in the US.  EGFR is an important target for anti-cancer therapies. Several EGFR inhibitors have recently been FDA approved for treatment of lung cancer. However, the inherent problem in the biology of lung cancer is the resistance of lung cancer cells to targeted therapies and only a limited population of lung cancer patients responds to the EGFR inhibitors. Dr. Krysan proposes that understanding the mechanisms of this resistance will likely lead to important advances in therapy for this devastating disease.

ATS/ Pulmonary Hypertension AssociationPartnership Grants in Pulmonary Hypertension

• Co-funded by the ATS and the Pulmonary Hypertension Association

Namasivayam Ambalavanan, MBBS, MD

University of Alabama at Birmingham
Research: “Transforming Growth Factor-β and Effects of Hypoxia on the Newborn Lung”

Persistent pulmonary hypertension of the newborn (PPHN) in term infants and bronchopulmonary dysplasia (BPD) in premature infants are major causes of death or long-term impairment in newborn infants.  Hypoxia (lack of oxygen) is a contributing factor to PPHN and BPD.  Both PPHN and BPD have abnormal development of the lung blood vessels, and BPD also has abnormal development of the lung air sacs.  Normal lung development is mediated by a growth factor called transforming growth factor-β (TGFβ).  Dr. Ambalavanan proposes that identifying how TGFβ mediates hypoxia-induced changes in lung development may help identify treatment strategies for BPD or PPHN and help improve newborn survival.

Arlin B. Blood, PhD

Loma Linda University
Research: “The Interaction of Nitric Oxide and Hemoglobin in the Regulation of Pulmonary Vascular Tone”

Pulmonary hypertension is a disease in which blood pressure between the heart and lung is elevated, sometimes due to constriction of the arteries carrying blood to the lung.  In severe cases, pulmonary hypertension can lead to impaired blood flow to the lungs and an inability to adequately oxygenate the blood.  Also, the additional work required by the heart to pump blood through the lung can lead to heart disease and failure.  Hemolysis is a condition in which red blood cells in the blood break open, spilling their contents into the plasma.  In severe hemolysis, the ability of the body to clear hemoglobin from the plasma is overwhelmed and hemoglobin in the plasma becomes a toxin.  Recent evidence indicates that free hemoglobin selectively constricts pulmonary arteries, leading to pulmonary hypertension.  Dr. Blood plans to develop a model of pulmonary hypertension caused by hemolysis to explore the mechanism and potential treatment options.

ATS Unrestricted Grants:

Vivek Balasubramaniam, MD

University of Colorado Denver Health Sciences Center
Research: “Role of Endothelial Progenitor Cells In the Development of BPD”

Premature infants suffer from a chronic lung disease of infancy known as bronchopulmonary dysplasia (BPD).  Interestingly, only 60 percent of infants born prematurely develop BPD.  Infants with BPD have abnormal lung structure, including impaired growth of the blood vessels in the lung. In the circulation of full term infants, there exists a population of cells that is progenitor or precursor cells that will grow into blood vessels called endothelial progenitor cells (EPCs).  This project will determine if there are differences in the number of these cells in a premature infant versus a full term infant.  Dr. Balasubramaniam hopes to identify differences in the function of EPCs from premature infants who develop BPD compared to those that do not.  These studies may provide insight into the development of BPD and lead to new therapies to reduce the morbidities of infants with BPD.

Jinhee Lee, DVM, PHD

University of Massachusetts
Research: “Lipsome-Based Tuberculosis Vaccine Enhanced by Immunostimulatory Ligands”

Tuberculosis (TB) kills millions of people despite the availability of effective antibiotics.  Two factors have dramatically increased the global threat of TB in recent decades: the HIV/AIDS pandemic and the emergence of antibiotic resistant TB germs.  The recent advent of extreme drug resistant (XMDR) TB makes it even more urgent to develop an effective vaccine.  BCG, the only currently available TB vaccine, has provided life-saving protection for certain forms of TB in children, but it is not effective for adults.  In an effort to develop a safer and stronger TB vaccine, Dr. Lee proposes a new approach of vaccine design that he believes will strongly activate immunity and improve patient compliance.

Benjamin D. Medoff, MD

Massachusetts General Hospital
Research: “The Role of the CARMA Proteins in Allergic Airway Inflammation”

Asthma is one of the most common chronic diseases in the world, affecting around five percent of the population.  Asthma results from an abnormal inflammatory response in the lungs to inhaled particles in the air.  Dr. Medoff plans to study the functions of the CARMA proteins in a mouse model of asthma.  The results of these studies will provide important information on the biology of these proteins.  It is hoped that the results may help identify novel targets of therapy for asthma.  Given the prevalence of asthma, new therapy for this disease could have a tremendous impact on the overall health of the public.

Magnus Nord, MD, PhD

Karolinska Institutet
Research: “C/EBP Transcription Factors-Novel Players in the Pathogenesis of COPD”

Chronic obstructive pulmonary disease (COPD) is a major and increasing global health problem that is now a leading cause of death.  In the US, 24 million adults have been estimated to suffer from this disease and the total societal cost has been estimated at 32.1 billion US dollars per year. There is a major need to develop new treatments for COPD as no currently available drug therapy reduces the relentless progression of the disease.  Dr. Nord proposes that his studies will serve to identify novel targets for the development of future innovative treatments.