ATS Research Grantees: Making Novel, Ground-breaking Research Discoveries

ATS Grants

ATS Unrestricted Research Grants:
These grants are funded by the American Thoracic Society. Current grant recipients:

	Shweta Choudhry, Ph.D. | University of California, San Francisco Research: “Whole Genome Association Study to Identify Asthma Related Genes in Puerto Ricans” Of all the U.S. populations, Puerto Ricans have the highest asthma prevalence, morbidity and mortality rates. Despite these dramatic differences in asthma morbidity and mortality very little is known about the genetic factors that contribute to asthma in this population. Dr. Choudhry will use a genetic technique called admixture mapping to try to identify genetic regions associated with susceptibility to asthma. Her studies will be the first application of this genetic technique in Puerto Rican populations. By gaining a better understanding of genetic factors which may be responsible for asthma among the Puerto Rican population, Dr. Choudhry’s findings could provide a way to identify individuals at high risk for morbidity and mortality from asthma.
	Patricia, J. Dubin, M.D. | Children’s Hospital of Pittsburgh Research: “Type I and III IFNs in Pseudomonas aeruginosa pneumonia” Dr. Dubin is studying P. aeruginosa, a type of bacteria that causes pneumonia, pulmonary damage and death in immunocompromised individuals and patients with cystic fibrosis. Current therapies against P. aeruginosa infection are inadequate, often targeted only at killing the bacteria. It has been determined that two chemicals the host makes, IL-23 and IL-17, are critical to fighting P. aeruginosa infection. IL-23 triggers the production of IL-17 and the recruitment of white blood cells that fight the infection. It is unclear how IL-23 production is regulated, but preliminary studies suggest that a group of signaling chemicals called interferons play a significant role in this. Preliminary studies show that type I interferons down-regulate IL-23 production and inflammation but that type III interferons actually up-regulate pro-inflammatory cytokines. Dr. Dubin will study whether manipulating interferon levels could change the host’s response to P. aeruginosa, and her work could lead to new treatments to help prevent lung damage from bacterial infection.
	William E. Lawson, MD | Vanderbilt University Medical Center Research: Defining the Origins of Effector Fibroblasts in Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis (IPF) is a severe lung disease in which patients develop the insidious onset of shortness of breath, decreased exercise capacity, scarring in the lung tissue, and difficulty with oxygen exchange. Once diagnosed, the outcome in most IPF patients is gradual progression to respiratory failure and death within a period of 3-5 years. Dr. Lawson is studying what proportion of new lung fibroblasts arise from cells in the bone marrow and what proportion arise from cells in the lungs. A better understanding of the origins of fibroblasts would allow physicians and scientists to identify specific targets that could lead to new therapeutic strategies to limit progression of disease in IPF and other forms of lung fibrosis.
	Hara Levy, M.D. | Brigham and Women’s Hospital; Children's Hospital Boston Research: “IL –1 gene family polymorphisms and susceptibility to P. aeruginosa in CF patients” Dr. Levy is studying why some people with cystic fibrosis (CF) develop very severe lung disease at an early age, while others have milder lung disease into adulthood. Progressive pulmonary disease associated with chronic bacterial infection and airway inflammation is the major cause of morbidity and mortality in cystic fibrosis (CF). CF lung disease is characterized by chronic infection by Pseudomonas aeruginosa. The basis for chronic infection is unknown, but both host and bacterial factors are likely to contribute. Dr. Levy hypothesizes that genetic variations may account for the differences in clinical course among patients with CF. The results of this study could eventually help to improve the treatment of patients with CF.
	Jingsong Xu, Ph.D. | Brigham and Women’s Hospital Research: “Role of Lysyl Oxidases (LOX and LOXL1) in Normal Lung Development” Dr. Xu is studying two proteins called LOX and LOXL1 that are important for matrix production during lung maturation. Lung maturation is a developmental process in which fetal and neonatal lungs develop open air spaces and get ready for gas exchange. This process is interrupted in premature babies. As a result, premature babies often develop breathlessness and hypoxia, which can be lethal. Dr. Xu’s studies are aimed at understanding the regulation of the normal lung maturation process, and using the normal regulators of development to promote lung maturation in adult patients. Studying the processes regulated by these two enzymes may lead to new ways to promote normal matrix production and lung maturation.

Acute Respiratory Distress Syndrome (ARDS)

ATS/The ARDS Foundation Partnership Research Grant:
This is a joint research award that is co-funded by the ATS and The ARDS Foundation. Current grant recipient:

Renee D. Stapleton, M.D., M.Sc. | University of Washington; Harborview Medical Center Research: “Anti-inflammatory Effects of n-3 Fatty Acids in Patients with Acute Lung Injury” Dr. Stapleton is performing a phase II randomized controlled trial which is the first attempt to provide a sound scientific basis for n-3 fatty acid administration in patients with Acute Lung Injury (ALI). This clinical trial will provide “proof of concept” using biologic endpoints that reflect lung inflammation, and will also lay the groundwork for a larger trial of nutritional therapy for patients with ALI. Dr. Stapleton hypothesizes that n-3 fatty acids will reduce lung and systemic inflammation, reduce organ failure, and show trends toward improvement in clinical outcomes in patients with ALI.

Alpha-1 Antitrypsin/COPD

ATS/Alpha-1 Foundation Partnership Research Grant:
These are joint research awards that are co-funded by the ATS and the Alpha-1 Foundation. Current grant recipients:

Harvey O. Coxson, Ph.D. | University of British Columbia Research: “Quantification of post-transplant bronchiolitis obliterans syndrome using CT scanning” Dr. Coxson will determine whether CT scanning is useful for the identification of bronchiolitis obliterans (BO) in lung transplant recipients, which is the major long-term complication of lung transplantation. Lung transplantation has become an important treatment option for certain carefully selected patients with alpha-one antitrypsin deficiency. BO affects over half of lung transplant patients and presents as progressive shortness of breath and is usually first identified using pulmonary function tests. CT scanning is a non-invasive, repeatable test which may be useful for identifying BO at a very early stage, when treatment may have the greatest likelihood of success.

Darrell N. Kotton, M.D. | Boston University Research: “Stem Cell-based Therapy for Alpha-1 Antitrypsin Deficiency” Dr. Kotton is working to develop a novel stem cell-based therapy for alpha-1 antitrypsin (AAT) deficiency. He will use lentiviral-mediated transfer of the normal human AAT gene into hematopoietic stem cells, or novel candidate liver progenitor populations, and then transplant these cells into mice in order to achieve stable and therapeutic secretion of AAT protein in lung tissue. If successful, this new approach could undergo safety testing and then be moved into future clinical trials of therapy for individuals afflicted with AAT deficiency.

COPD

ATS Research Award for Novel Studies of COPD:
This is an ATS research program that is sponsored by The Respiratory Institute, a Division of GlaxoSmithKline. Current grant recipients:

Janet Lee, M.D. | University of Pittsburgh Fractalkine/CX 3CL1: A Novel Pathway Related to the Pathogenesis of COPD Dr. Lee is studying chronic obstructive pulmonary disease (COPD), a chronic lung disease characterized by chronic inflammation in the airways. Although cigarette smoking is the most important risk factor for COPD, the majority of smokers do not develop COPD. Several human studies implicate a role for immune cells called T lymphocytes in the pathogenesis of cigarette-induced COPD. Dr. Lee will investigate the role of a new protein, fractalkine, in the development of cigarette-induced COPD, and its role in the recruitment of T lymphocytes into the lungs. Defining the biological significance of fractalkine in the lungs will provide novel information about the mechanisms underlying the development of COPD and identify potential therapeutic targets for this important disorder.

Chun Geun Lee, M.D., Ph.D. | Yale University Genetic Factors Controlling TGF-ß 1 in the Pathogenesis of COPD Transforming Growth Factor-ß 1 is a multifunctional molecule that plays a critical role in tissue injury, inflammation and repair, and is overexpressed in tissues of patients with COPD. To define the role of TGF-ß 1 in COPD, Dr. Lee and his colleagues generated mice in which TGF-ß 1 was selectively overexpressed in the lung. They will use these mice to investigate the role of TGF-ß 1 in pulmonary fibrosis and emphysema. Results from this research could provide important new information about the role of TGF-ß 1 and the genetic determinants of susceptibility to emphysema.

Lymphangioleiomyomatosis (LAM)

ATS/The LAM Foundation Partnership Research Grant:
This is a joint research award that is co-funded by the ATS and The LAM Foundation. Current grant recipient:

Arnold S. Kristof, M.D. | The Research Institute of the McGill University Hospital Centre Research: ”The Role of Protein Kinase Cδ in the Pathogenesis of Lymphangioleiomyomatosis” Dr. Kristof’s studies will enhance our knowledge about why lymphangioleiomyomatosis (LAM) progresses, and how to treat patients with this important disease. LAM is a disease that causes destruction of the lungs, failure of the respiratory system, and need for lung transplantation. LAM is caused by abnormal growth of smooth muscle cells, which leads to lung cysts and abdominal tumors. Dr. Kristof is using molecular and cellular biology techniques to understand how a signaling molecule called mTOR helps cells choose between increased growth or premature death. These ‘signaling switches’ could be exploited to promote the death of abnormal LAM cells. These molecular switches and potential therapies might also control abnormal smooth muscle growth in other lung diseases, such as asthma.

Lung Cancer

ATS/LUNGevity Foundation Clinical Research Grant in Lung Cancer:
These are joint research awards that are co-funded by the ATS and the LUNGevity Foundation. Current grant recipients:

Charles A. Powell, M.D. | Columbia University Molecular Signatures of Invasiveness in Lung Adenocarcinoma Dr. Powell’s research focuses on understanding lung cancer, the leading cause of cancer death in the U.S and the world. He is working to understand the molecular events involved in progression of adenocarcinoma, which represents 40 percent of all lung cancers. Dr. Powell’s long-term goal is to discover biomarkers that are associated with invasiveness of adenocarcinoma. These new biomarkers will facilitate early diagnosis, refine the assessment of prognosis, and assist in the development of new therapeutic targets for lung cancer.

George M. Verghese, M.D. | University of Virginia Regulation of Non-small Cell Lung Cancer Invasion by Membrane Serine Proteinases and Antiproteinases Dr. Verghese’s research focuses on non-small cell lung cancer. The major goals of his research are to identify new biological markers for non-small cell lung cancer that will correlate with tumor type, stage and behavior, and to define a new cell-surface protease pathway that regulates the spread of lung cancer cells. The findings from this research may lead to the development of tests to screen for early lung cancer and to new targets for drug development that could slow or stop the progression of many forms of lung cancer.

Pulmonary Hypertension

ATS/Pulmonary Hypertension Association Partnership Grant:
These are joint research awards that are co-funded by the ATS and the Pulmonary Hypertension Association. Current grant recipients:

Todd M. Bull, M.D. | University of Colorado Denver HSC Research: “The role of Kaposi’s sarcoma herpesvirus (HHV-8) in the development of severe pulmonary hypertension” Dr. Bull is investigating mechanisms by which HHV-8 contributes to the development of severe pulmonary hypertension. Severe pulmonary arterial hypertension (PAH) is a poorly understood disease with severe clinical consequences for those afflicted. The disease process of PAH is characterized by an abnormal growth of cells in the pulmonary arteries. The ability of HHV-8 to infect pulmonary microvascular endothelial cells has already been demonstrated. Dr. Bull will investigate the effect of this infection on the gene and protein expression of these cells as well as the effect on cell growth and cell apoptosis (programmed cell death). Dr. Bull will also explore a possible connection between HHV-8 infection and alterations in the bone morphogenic protein (BMP) pathway, a pathway recognized to be important in the development of pulmonary hypertension.

Xinqi Wu, Ph.D. | Children’s Hospital Boston Research: “Hypoxic regulation of bone morphogenetic protein (BMP) signaling and the role of Id1 in the development of pulmonary hypertension” Dr. Wu hypothesizes that the suppression of the signaling molecule, Id1, may cause increased growth and inhibition of apoptosis of human pulmonary artery smooth muscle cells (HPASMC) contributing to the development of Pulmonary Hypertension. Primary pulmonary hypertension (PPH) is a fatal disorder characterized by excessive growth of blood vessel cells in the lungs, resulting in narrowing of vessels and increased blood pressure in the lungs followed by heart failure. Dr. Wu is investigating Id1 expression in hypoxic lungs of mice and the role of Id1 in cell cycle progression, proliferation, apoptosis and migration, processes underlying vascular remodeling. Dr. Wu’s studies will identify additional hypoxiaregulated BMP target genes, enhance our understanding of PPH pathogenesis and may lead to the identification of molecules that play a critical role in PPH, and could be targets for therapeutic intervention.

ALA/ATS Career Investigator Award

This is a joint research award that is co-funded by the ATS and the American Lung Association. Current grant recipient:

Lynn Schnapp, M.D. | University of Washington HIV-Matrix Interactions in the Lung Dr. Schnapp is performing studies to investigate the mechanisms by which the human immunodeficiency virus (HIV) induces inflammation and replicates in the lungs. The lungs are a key target of HIV infection, and many patients who progress to AIDS develop severe pulmonary infections. Dr. Schnapp has discovered that HIV-infected lymphocytes produce signals that stimulate fibroblasts to produce matrix molecules like fibronectin, which are part of the backbone structure of the lungs. Dr. Schnapp’s studies will determine how fibronectin binds to the HIV virus, and how this interaction stabilizes the virus, prolonging infectivity. These studies will enhance our knowledge of the basic molecular mechanisms involved in HIV infection, and could suggest new molecular targets for combating HIV infection in the lungs.

Sarcoidosis

American Thoracic Society/Foundation for Sarcoidosis Research Partnership Grant for Sarcoidosis:
These are joint research awards that are co-funded by the ATS and the Foundation for Sarcoidosis Research. Current grant recipients:

Jan A. Wahlström, M.D., Ph.D. | Karolinska Institutet Research: “Antigen specificity in Sarcoidosis” Sarcoidosis is a chronic inflammatory disease of unknown origin which affects the lungs and other organs. The T cells are the cells of the immune system that are believed to be central for initiating and maintaining the inflammation. Dr. Wahlström has identified a distinct population of T cells in the lungs of a clinically and genetically well characterized group of patients. Dr. Wahlström hypothesizes that these T cells have recognized and proliferated in response to a specific “sarcoidosis antigen”. Dr. Wahlström and his associates have been able to identify small peptides that are presented to the T cells in the lungs of these patients. This collection of peptides provides a unique opportunity to identify a sarcoidosis antigen, which could lead to a new understanding about how the disease occurs.

Richard F. Silver, M.D. | Case Western Reserve University Research: Abnormal TLR responses in the pathogenesis of pulmonary Sarcoidosis Sarcoidosis is an inflammatory disease of unknown cause that can affect many organs of the body. The lungs are the most frequent site of disease. Currently, the main treatment for sarcoidosis is the administration of anti-inflammatory corticosteroids. This treatment is frequently effective, but because it is not specific, it can lead to many unwanted and harmful side effects. Dr. Silver will investigate how white blood cells from the lungs of sarcoidosis patients recognize bacterial products using Toll-like receptors (TLR). If the proposed studies show that TLR responses of lung cells of patients with sarcoidosis are excessive, new treatments could be developed based on modifying TLR function. This could result in new approaches to treating patients with sarcoidosis.

Transplantation

ATS/American Society of Transplantation Research Partnership Grant:
This is a joint research award that is co-funded by the ATS and the American Society of Transplantation. Current grant recipient:

Stavros Garantziotis, M.D. | Duke University Research: “The role of innate immunity in alloimmune lung injury after transplantation” Dr. Garantziotis is studying the role of the innate immune system in lung rejection after transplantation. This study represents as an important step towards a better understanding of the mechanisms that render the lung highly vulnerable to immune injury. The study will identify risk factors for posttransplant injury as well as provide information about how to modify immunosuppressive treatment. The results could lead to novel therapies to prevent lung rejection and improve the outcomes of patients who undergo lung transplantation.

Our Research Program Partners

A guiding principle of the ATS Research Program is that it will work in partnership with other medical, research, clinical, professional, corporate, patient and non-profit health organizations that are focused on the diagnosis, understanding and treatment of lung disease. Our current research partners, who share research priorities and funding responsibilities, are:

Alpha-1 Foundation*
American Lung Association
American Society of Transplantation
The ARDS Foundation*
The Foundation for Sarcoidosis Research
The LAM Foundation*
LUNGevity Foundation
Pulmonary Hypertension Association*
The Respiratory Institute, a Division of GlaxoSmithKline

The ATS welcomes our newest partners:

American Lung Association of Hawaii
Asthma and Allergy Foundation of America*
Coalition for Pulmonary Fibrosis*
COPD Foundation*

*These organizations are public interest organizations and members of the ATS Public Advisory Roundtable.