Nine researchers at the University of Virginia have been awarded a total of $10 million over three years from the UVA 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 (PM USA) to the University.
In an innovative move, under the terms of the PM USA agreement with UVA, an External Advisory Board of independent physician/scientists has been established to review the structure and administration of the grants program, including the application and review process. Board members may not be currently or previously affiliated with UVA, any tobacco company, or any other person or entity that presents a conflict of interest with the University or PM USA. This arrangement is similar to that used by many states when distributing funding provided by tobacco companies under the Master Settlement Agreement. Grant awards are based on evaluation and ranking by external and internal reviewers
“We have long understood that smoking causes extensive damage to our bodies. What have not been studied are the mechanisms by which smoking causes diseases such as lung cancer, chronic obstructive pulmonary disease (COPD), and emphysema,” says Erik Hewlett, M.D., Senior Associate Dean for Research at UVA. “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. 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 US.
One example of the planned research is that of Associate Professor of Pediatrics John F. Hunt, M.D., who plans to use his 3-year grant to study the role of airway acid stress in acute exacerbations of COPD.
“Smoking appears to contribute to the lung injury that allows simple colds to cause severe acute breathing problems in patients with COPD. The colds may be contributing to the acid stress which is not tolerated well in an injured lung,” Hunt explains.
Acid in a person’s airway comes from inhaling stomach acid and from acid made in the lungs themselves. This acid can cause injury to and inflammation of the airway, which is called “acid stress.”
The grant will allow Hunt to more fully characterize airway acid stress in the COPD population. 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 which contribute to or cause respiratory disease.
“It is a shame to spend lots of taxpayer money on studies of how cells work in the lung during disease when the critically important issue of pH (acidity) is forgotten. The pH will affect whatever the researchers are studying, making the research of less value,” Hunt adds.
The researchers have full independence to publish their work without contact with representatives of PM USA.
In addition to Hunt, the following researchers received three-year grants from the UVA Tobacco Research Program:
Stuart S. Berr, PhD
Imaging methodologies to study smoking induced inflammation and cancer
Development of 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, PhD
A proteomic comparison of normal and dense breast stromal matrix and the
role of inflammation on stromal matrix structure and functionality
Investigation of 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.
David R. Jones, MD
Regulation of the “metastasis-suppressor gene,” BRMS1, in lung cancer
Examination of 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, PhD
Cigarette smoke-induced formation of endogenous TLR-2 activators
Examination of 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, PhD
Smoking-induced erectile dysfunction
Exploration of 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, PhD
Identification of NF-κB-regulated biomarkers in lung cancer stem cells
Study of 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, PhD
P-LISA, a novel method to generate biomarkers for lung tumors
Examination of how a key mitotic regulatory complex may influence tumor progression and its use in discovering new biomarkers for lung tumors.
Michael P. Timko, PhD
Alteration of the human lung transcriptome by discrete smoke constituents
Determination of 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.