JANET THOMAS, PhD
University of Minnesota, Minneapolis, MN
Social Behavioral Research Grant Co-funded by the American Lung Association and the American Lung Association of the Upper MidWest

Comparing Two Methods To Encourage Home Smoking Bans

Documenting Child Exposure To Environmental Tobacco Smoke (ETS) Carcinogens: A Novel Approach To Motivate Families To Adopt Home Smoking Bans.Exposure to secondhand smoke contributes to about 50,000 deaths in the United States each year and is a recognized cause of respiratory disease in children. Yet 36.1% of children in the U.S. live in a home where people regularly smoke cigarettes. One way to reduce childrens secondhand smoke exposure is by limiting or banning smoking in the home. The researchers will evaluate two methods to motivate families to adopt home smoking restrictions. One group will receive a home visit by a counselor who will provide a brochure documenting the health impact of home exposure to secondhand smoke. The second group will receive the same brochure and will be given more education from the counselor about the health risks of home smoking and the importance of a home smoking ban. The second group will also receive the results of a lab test conducted on the urine of a child in the home that will document cotinine (a byproduct of nicotine use) and NNAL, a known cancer-causing agent found only in tobacco. Three months later, the researchers will return to see if the method the smokers received changed their home smoking policies and if the treatment had any effect on their smoking behaviors.

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JIAN ZHANG, MD
University of Chicago, Chicago, IL
Career Investigator Award Funded by the American Lung Association of the Upper Midwest

Controlling IgE Production Key To Treating Allergic Asthma

Regulation Of IgE Production By E3 Ubiquitin Ligase Cbl-b.The body releases immunoglobulin E (IgE) antibodies when it comes in contact with an allergen such as dust, pollen or mold spores. For most allergy sufferers, the release of IgE produces symptoms such as a runny nose, sneezing, and itchy or watery eyes. However, for those with allergic asthma, the release of IgE can trigger a full-blown asthma attack. Therefore, controlling IgE levels is crucial for treatment of allergic asthma. The researchers will study a specific protein, called Cbl-b, and determine whether and how it regulates factors that control IgE production. This research could provide information that will lead to better treatments for allergic asthma.

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KONSTANTIN BIRUKOV, MD, PhD
University of Chicago, Chicago, IL
Career Investigator Award Co-funded by the American Lung Association and the American Lung Association of the Upper Midwest

Can A Drug Used To Protect Against Radiation Damage Also Treat Lung Injury?

Novel Strategies For Treatment Of Acute Lung Injury Using Radiation Protector Amifostine. Acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are types of severe, acute lung dysfunction affecting all or most of both lungs that occur as a result of illness or injury. ARDS has a case fatality rate of 25-40%. Despite recent progress in treatment of ALI, there is still no satisfactory strategy to reduce lung damage and tissue injury in this condition. The researchers will study the compound amifostine, a drug used to control some side effects of chemotherapy and radiation therapy, to see whether it can significantly reduce ALI induced by infectious agents. Amifostine belongs to a group of agents called cytoprotectants, which protect normal tissue from some of the side effects caused by treatments for cancer. The researchers believe that studying ami-fostines protective effects may bring a promising direction in drug discovery aimed at the development of new drugs for prevention of pulmonary edema (fluid in the lungs) as a result of acute lung in-flammation and trauma.

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ANNA BIRUKOVA, MD
University of Chicago, Chicago, IL
Biomedical Research Grant Co-funded by the American Lung Association and the American Lung Association of the Upper Midwest

Growth Factor May Play Role In Treating Acute Lung Injury

Cell Adhesions In Hepatocyte Growth Factor-Induced Lung Endothelial Barrier Protection. Acute respiratory distress syndrome (ARDS) remains a major cause of illness and death. During the acute phase of lung injury, protein-rich fluid can flow into the spaces between the air sacs in the lung, causing pulmonary edema, or fluid in the lungs. A protein called hepatocyte growth factor (HGF) is one substance that appears in the lung after acute lung injury, and regulates a wide variety of events. Recent studies have suggested an important role of HGF in protecting against this fluid leak in the lungs. The researchers will study whether HGF can play a key part in significantly reducing the acute phase of ARDS associated with increased fluid leak in the lungs. If so, the findings would suggest a potential role for HGF in treating acute lung injury.

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NAVDEEP CHANDEL, PhD
Northwestern University, Chicago, IL
Career Investigator Award Funded by the American Lung Association of the Upper Midwest

Evaluating Immune System Proteins Role In Acute Respiratory Distress Syndrome

Mitochondrial ROS Regulation of TGF-Beta 1 Induced Gene Expression. There is no effective treatment for patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). These disorders are associated with an unacceptably high death rate. Transforming growth factor-beta 1 (TGF-B1) has been identified as a critical immune system protein regulating tissue repair in animal models of lung injury and scarring. Too little TGF-B1 activity may prevent resolution of inflammation and impair tissue repair while too much activity may lead to fibrosis, or scarring in the lungs. The researchers will study the relevance to lung disease of a chemical signaling pathway in TGF-B1. The results may provide the rationale for developing and testing novel therapeutic strategies for ARDS and ALI.

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PATRICK A. SINGLETON, PhD
University of Chicago, Chicago, IL
Biomedical Research Grant Co-funded by the American Lung Association and the American Lung Association of the Upper Midwest

Knowing Why Cell Barrier Is Disrupted May Lead To ARDS Treatment

HABP2/C1INH Regulation Of Acute Lung Injury. Acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are types of severe, acute lung dysfunction affecting all or most of both lungs that occur as a result of illness or injury. ALI/ARDS afflicts over 190,000 people a year in the U.S., resulting in 74,500 deaths. Despite recent progress in treatment of ALI, there is still no satisfactory strategy to reduce lung damage and tissue injury in this condition. The hallmark of ALI is inflammation-induced disruption of the cells called endothelial cells that line the pulmonary blood vessels, linking to one another with cell-cell junctions to form a physical barrier between the airways and the blood vessels of the lung. This disruption results in leakage of fluid, protein, and cells into the airspaces of the lung. The researchers seek to understand the mechanisms of the endothelial cell barrier disruption in an attempt to develop novel strategies to treat ALI/ARDS.

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LIN-FENG CHEN, PhD
University of Illinois at Urbana-Champaign, Champaign, IL
Biomedical Research Grant Co-funded by the American Lung Association and the American Lung Association of the Upper Midwest

Targeting Protein That Causes Inflammation In Asthma And COPD

Regulation And Functions Of Reversible Acetylation Of NF-kappa B In Lung Inflammation. Lung inflammatory diseases, including chronic obstructive pulmonary disease (COPD) and asthma, are characterized by an increased production of genes that cause inflammation. These genes are mainly controlled by a protein called NF-kappa B. Blocking this protein could be a novel treatment in these diseases. Many currently used anti-inflammatory drugs for asthma and COPD, such as steroids, indirectly inhibit NF-kappa B. The researchers will investigate how NF-kappa B is regulated, learn about its role in inflammation, and identify targets for treatment that would inactivate the protein.

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BEATRIZ QUINCHIA-RIOS, PhD, DDS
University of Wisconsin, Madison, WI
Senior Research Training Fellowship Funded by the American Lung Association of the Upper Midwest

Airway Remodeling Research May Benefit Patients With Asthma

Role of the IL-5 Activated Eosinophil In Airway Remodeling Through Modulation Of Bronchial Fibroblasts Activation Of A Fibrotic And Secretory Phenotype. The persistence of asthma may lead to progressive changes in the airway that affect air intake, worsen asthma symptoms and irreversibly damage breathing function. These structural changes in the airway are collectively known as airway remodeling. Treatment with anti-inflammatory drugs such as corticosteroids can improve asthma symptoms but has a limited long-term effect on airway remodeling; therefore, it is important to investigate the factors that trigger and perpetuate airway remodeling in order to create better therapies to control or prevent these changes. One of the major inflammatory cells involved in the allergic asthma reaction and recently linked to some features of airway remodeling is the eosinophil. This cell is activated by the presence of an inflammatory protein, IL-5, and its activation may affect the behavior of the resident cells causing remodeling. The researchers will study the role of IL-5-primed eosinophils in altering the resident cells and causing airway remodeling. This research will contribute to our understanding of the causes as well as the process of airway remodeling, and should be important for the design of more specific medications and treatment strategies to control and perhaps prevent airway remodeling, including anti-IL5 agents.

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LIN-FENG CHEN, PhD
University of Illinois at Urbana-Champaign, Champaign, IL
Biomedical Research Grant Co-funded by the American Lung Association and the American Lung Association of the Upper Midwest

Targeting Protein That Causes Inflammation In Asthma And COPD

Regulation And Functions Of Reversible Acetylation Of NF-kappa B In Lung Inflammation. Lung inflammatory diseases, including chronic obstructive pulmonary disease (COPD) and asthma, arecharacterized by an increased production of genes that cause inflammation. These genes are mainly controlled by a protein called NF-kappa B. Blocking this protein could be a novel treatment in these diseases. Many currently used anti-inflammatory drugs for asthma and COPD, such as steroids, indirectly inhibit NF-kappa B. The researchers will investigate how NF-kappa B is regulated, learn about its role in inflammation, and identify targets for treatment that would inactivate the protein.

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KEVIN LEGGE, PhD
University of Iowa, Iowa City, IA
Biomedical Research Grant Co-funded by the American Lung Association and the American Lung Association of the Upper Midwest

Finding A Way To Help The Immune System Fight Off Bacterial Infections After Influenza

Respiratory Dendritic Cells: Cell Migration And Induction Of Adaptive Immunity During Virus Infections. The lungs are routinely exposed to foreign pathogens such as bacteria and viruses in the air that we breathe. Often our immune system halts these pathogens before significant infections can occur. However, when these pathogens do establish an infection, the immune system must kick in to fight it. In the lungs, respiratory dendritic cells (rDC) are thought to be responsible for inducing this immune system response. The researchers have found that following influenza infections, rDC rapidly migrate from the lungs to the lymph nodes and induce an immune response that is specific to influenza. But within 24 hours after influenza virus infection, rDC halt their migration. This halt is of particular concern following respiratory virus infections where concurrent or new bacterial infections are common. The researchers will study the way in which rDC migration is stopped following influenza virus infections. They will then determine if manipulating this mechanism can restore rDC migration, thus helping the immune system fight off secondary infections. By boosting the immune systems response to bacterial infections, complications ranging from otitis media and pneumonia in children to potentially deadly pneumonia in elderly adults might be avoided.

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LATANIA LOGAN, MD
Childrens Memorial Hospital, Chicago, IL
Senior Research Training Fellowship Funded by the American Lung Association of the Upper Midwest

How Do Hardy Bacteria In The Lung Withstand Antibiotic Treatment?

Mechanisms of Relapse In Pseudomonas Aeruginosa Acute Pneumonia. Pseudomonas aeruginosa (PA) is a bacteria that is a major cause of lung disease resulting in serious infections. This organism is particularly problematic in patients with hospital-acquired pneumonia, which leads to death in up to 80% of infected patients on ventilators. PA is very difficult to kill once it has infected the lung, and often causes relapses. Most cystic fibrosis patients remain infected with the same strain of PA for life despite long-term therapy with multiple antibiotics. Despite the enormity of the problem, very little is known about how PA is able to withstand antibiotic therapy. The researchers will examine what happens to the bacteria inside white blood cells during antibiotic treatment. A better understanding of the importance of PAs role inside white blood cells in pneumonia may lead to the identification of new antibiotic combinations with increased effectiveness in the treatment of these infections.

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RICHARD NHO,PhD
University of Minnesota, Minneapolis, MN
Biomedical Research Grant Funded by the American Lung Association of the Upper Midwest

Spotlight On Cell That May Be Responsible For Scarring in Pulmonary Fibrosis

A Pathologic Integrin Growth Signaling Pathway Regulates Aberrant IPF Fibroblast Proliferation On Extracellular Matrices. Idiopathic pulmonary fibrosis (IPF) is a deadly lung disease of unknown cause. Short of lung transplantation there is no proven effective treatment for the disease process. IPF is characterized by progressive scarring of the lungs. The primary cell type responsible for the progressive scarring is the lung fibroblast. Recent work suggests that the lung fibroblast in IPF has distinct properties enabling it to abnormally proliferate and survive. However, much is still not known about the differences between the out-of-control growth of fibroblasts in IPF responsible for progressive proliferation and the limited production of normal fibroblasts necessary for proper lung repair. In preliminary studies, the researchers have discovered abnormal changes in chemical pathways that regulate IPF fibroblast proliferation. The researchers will further investigate key differences between normal and IPF fibroblasts that underlie the ability of IPF fibroblasts to proliferate and scar the lungs. These experiments could suggest new therapeutic strategies for this lethal disease.

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SERGEI DANILOV, MD, MPH
University of Illinois, Chicago, Chicago, IL
Career Investigator Award Co-funded by the American Lung Association and the American Lung Association of the Upper Midwest

Uncovering Enzymes Role In Pulmonary Hypertension

Role Of Caveolin-1 In Lung Endothelial ACE Expression. Pulmonary hypertension, or high blood pressure affecting the pulmonary blood vessels, is difficult to treat and is usually fatal within a few years of diagnosis. The cells that make up the inside layer of the lung blood vessels, called dysfunctional pulmonary endothelium, have a central role in the initiation and progression of severe pulmonary hypertension. The researchers previously have shown that an enzyme called angiotensin-1-converting enzyme (ACE), which is involved in the regulation of blood pressure, plays a role in the development of pulmonary hypertension. They will study abnormalities in structures called caveolae that are found in endothelial cells, to see if they affect ACE production and function in lung blood vessels. The researchers believe that better understanding the mechanisms that govern production of ACE in the lung will greatly enhance the understanding of the development of pulmonary hypertension and facilitate the development of new, effective treatments of this severe lung disease.

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FARAHNAZ MOVAHEDZADEH, PhD
University of Illinois, Chicago, IL
Biomedical Research Grant Co-funded by the American Lung Association and the American Lung Association of the Upper Midwest

Genes May Provide Insight About Latent Tuberculosis

The Biological Function Of Genes Essential For Latency In M. Tuberculosis. Mycobacterium tuberculosis (Mtb) causes tuberculosis (TB), which kills 1.7 million people worldwide every year. TB can reside latently in the human body for many years, but once active, it attacks the respiratory system. Anti-TB therapy is complicated, involving combinations of antibiotics taken over 6-12 months. In certain parts of the world, the rates of drug resistance are increasing rapidly. Thus, there is an urgent need to identify new anti-TB drugs. The ability of Mtb to enter a latent state is considered to be the key to its success as an infectious agent. The researchers will study the mechanism of the genes which are important in maintenance of the latent state of Mtb. Determining the functions of such genes will be key to finding targets for new anti-TB drugs that eliminate latent TB infection and/or shorten the duration of treatment of active TB.

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