A three-year, $750,000 research grant that specifically encourages researchers to think “outside the box” will allow a team of University of Iowa investigators to apply findings from existing heart studies to research and study asthma.
Isabella Grumbach, MD, cardiologist at University of Iowa Hospitals and Clinics, talks about the study:
How competitive is the Strategic Program for Asthma Research or SPAR grant?
It is surprising competitive. We were told that the SPAR Foundation received 255 applications this year and funded 17 of these applications—a success rate of less than 7 percent. One in 15 applications was funded. To give you an idea of what this means, look at the National Institute of Health programs. The National Institute of Health usually fund between 15 to maybe 25 percent of all applications. So this has been quite a great success for us.
What is different about this particular grant?
It is strikingly different from most grant programs that require the applicant to demonstrate substantial expertise in the particular field or questions he or she is applying for. The SPAR Foundation explicitly encourages people who don’t know anything about asthma to apply. They ask people to be highly original in their thinking and to step away from the current area of interest.
What will this study look at specifically?
We will look at a particular protein, calcium calmodulin-dependentkinase II or CaMKII. Fancy name for a protein that is activated by calcium and in heart and blood vessel muscles it influences contraction, pathologic growth, and inflammation. We in the Division of Cardiovascular Diseases have a lot of experience studying CaMKII, mainly under the leadership of Mark Anderson, MD PhD, who a leader in the field of CaMKII. We have found that airway small muscle cells express abundant CaMkinase or have a great quantity of CaM kinase and physicians studying asthma are particularly worried about contractions, pathologic roles, and inflammation in smooth muscles cells. These are exactly the subjects that we in the heart and vascular field have been studying in the context of CaM kinase. So our belief is that CaM kinase may play the same role in airway smooth muscles cells and in asthma, and we hope that blocking this particular protein may be a completely new approach to treating asthma.
What role does calcium plays in heart disease?
It plays an enormous role. The heart wouldn’t beat without calcium and, in fact, no other muscle cell would contract without calcium. The heart beats about 60 to 100 times a minute and 60 to 100 times a minute the concentration of calcium in the heart muscle cell increases and as the cell contracts the concentration decreases and the heart muscle relaxes. The concentration of calcium inside the heart muscle cell is very, very tightly regulated and CaMKII has a very important role in regulating the concentration of calcium inside the cell. We know that in patients with heart disease—for example, heart failure—the concentrations of calcium in the heart muscle cell are increased and that CaMKII is particularly active. Dr. Anderson’s work has shown that blocking CaMKII can prevent these territorious changes inside the heart muscle, structure changes, and blocking CaM kinase can also prevent arrhythmias and sudden death.
How will you use the information previously gathered in studying heart disease to look at asthma?
We have developed a number of tools to study CaM kinase in great detail, including CaM kinase blockers, imaging techniques to check calcium inside the cells activity, and mice that do not have active CaM kinase. We will study airway smooth muscle cells, and we will study the mice that we have and look at their lung function.
What is the hope or premise of the research with regard to people with asthma?
Our hope is that blocking CaM kinase will prevent inflammation and pathologic growth in airway smooth muscle cells and this may be beneficial for patients with asthma. We’re really looking at a completely new idea on how to treat asthma.
What other specialties within The University are included in the team that will be working on this study?
Apart from the four cardiovascular scientists, there will be a pulmonologist—lung specialist—who will complement our studies. Joel Kline, MD, in the Division of Pulmonary Diseases is a specialist on asthmatic mice. He works a lot with asthmatic mice and can measure the lung function in these mice. These studies will be very important experiments for this study overall.
How important is having a multi-disciplinary team in getying grants like this one from SPAR?
I think it is extremely important. Of course, we want to come up with new and fresh ideas to study asthma. On the other hand, we would like to ask and answer questions that our colleagues in pulmonary disease—the lung specialists—are interested in. The participation of a lung specialist helps us stay on track and gear our studies toward questions that are of real importance for asthma research.
Will the three-year study be performed in labs, or will there be patient involvement?
At this point, all studies will be performed in different labs within the different divisions. Our hope is that we will be able to show that blocking CaMKII will be beneficial for asthma in mice and in cells and we hope that this data then can be used to plan for studies in patients in the future. |
