U.Va. Program Awards $10 Million to University Investigators to Studying Diseases Associated with Smoking

July 18, 2008 — Nine researchers at the University of Virginia have been awarded a total of $10 million over three years from the U.Va. Tobacco Research Program to advance the study of diseases associated with smoking.

The program was created in 2007 following a gift from Philip Morris USA to the University.

Grant awards are based on evaluation and ranking by external and internal reviewers. The researchers have full independence to publish their work without contact with representatives of Philip Morris.

Under the terms of the Philip Morris agreement with U.Va., an external advisory board of independent physician/scientists reviews the structure and administration of the grants program, including the application and review process.

Board members may not be currently or previously affiliated with U.Va., any tobacco company or any other person or entity that presents a conflict of interest with the University or Philip Morris. This arrangement is similar to that used by many states when distributing funds provided by tobacco companies under the Master Settlement Agreement.

"We have long understood that smoking causes extensive damage to our bodies," Dr. Erik Hewlett, senior associate dean for research at U.Va, said. "What have not been studied are the mechanisms by which smoking causes diseases such as lung cancer, chronic obstructive pulmonary disease and emphysema."

"Our researchers have chosen to focus on lung cancer, genetics, biomarkers and the important relationships between smoking and inflammation in this first round of grants," he added. "We believe that this work will lay the foundation for the understanding and treatment of smoking-related diseases.”

Smoking is the leading cause of preventable death and, according to the Centers for Disease Control, smoking-related diseases are responsible for more than $150 billion in annual health-related expenses in the United States.

One example of the planned research is that of Associate Professor of Pediatrics Dr. John F. Hunt, who plans to use his three-year grant to study the role of airway acid stress in making cases of chronic obstructive pulmonary disease worse.

"Smoking appears to contribute to the lung injury that allows simple colds to cause severe, acute breathing problems in patients with COPD," he explained. "The colds may be contributing to the acid stress which is not tolerated well in an injured lung."

Acid in a person's airway comes from inhaling stomach acid and from acid made in the lungs themselves. This acid can cause injury and inflammation in the airway, which is called "acid stress."

The grant will allow Hunt to more fully characterize airway acid stress in COPD patients.. In addition, he plans to conduct clinical studies with a simple, inexpensive therapy directed toward the excessive acidity, which may allow commonly prescribed inhaled medications to be more effective.

He hopes his work will encourage researchers, and later clinicians and patients, to pay attention to airway acid-base balance as they attempt to learn about the cellular and biochemical changes that contribute to or cause respiratory disease.

Hunt said his findings should make research into lung diseases more valuable. "It is a shame," he said, "to spend lots of taxpayer money on studies of how cells work in the lung during disease when the critically important issue of acidity is forgotten."

In addition to Hunt, the following researchers received three-year grants from the U.Va. Tobacco Research Program:

• Stuart S. Berr is developing imaging methodologies for use in identifying the relationship between inflammatory mediators induced by cigarette smoke and the subsequent development and progression to cancer and to other smoking-induced diseases.
• Jay W. Fox is investigating the chemical and structural differences between normal and dense breast tissue and the relationship between breast density and a chronic inflammatory state, which can be associated with both smoking and progression to breast cancer.
• Dr. David R. Jones is examining "the relationship between smoking and inflammation with the transition of bronchial epithelial and lung cancer cells to a metastatic state, and exploration of agents that might block this transition.
• Norbert Leitinger is examining the mechanisms by which cigarette smoke causes oxidative reactions and initiates crucial events in the development of arterial plaques, a process typified by chronic inflammation.
• Jeffrey J. Lysiak is exploring how oxidative stress induced by chronic smoking disrupts normal oxygen homeostasis in the lining of vascular tissue, to identify the underlying smoking-induced mechanisms causing ED via molecular, biochemical and in vivo approaches.
• Marty W. Mayo is studying the molecular mechanisms controlling the epithelial to mesenchymal transition, which is critical for lung cancer progression, invasive growth and metastasis of lung cancer cells.
• P. Todd Stukenberg is examining how a key mitotic regulatory complex may influence tumor progression and its use in discovering new biomarkers for lung tumors.
• Michael P. Timko is examining how individual smoke components change lung cell function, with the goal of developing strategies to prevent, alleviate or reverse the harmful cellular effects and debilitating consequences of smoking on human health.