Matthew Drake, M. D. is an assistant professor of pulmonary medicine with a special focus on asthma and critical care. His research focuses on airway neurobiology and innate immunity in asthma, with a particular focus on Toll-like receptors.
Where are you from originally?
I was born in Cambridge, England, but moved to Tucson, Arizona, at a young age. My parents both worked for the University of Arizona and enjoyed being as far away from the rain and cold as possible.
What brought you to OHSU?
I came to Portland for a residency in internal medicine and decided to stay for a variety of reasons. I knew early on that I wanted a career in pulmonary and critical care medicine that included a focus in basic science airway research. OHSU’s pulmonary division has an stellar reputation in both areas. I’m fortunate to have outstanding mentors in Drs. David Jacoby and Allison Fryer who have been instrumental in my career development at every stage.
What drew you to pulmonary critical care and research?
I am fascinated by lung physiology and immunology. The lungs are constantly bombarded by the environment. Their response to that exposure is quite diverse and can often be pathologic. Asthma is a great example of an abnormal airway immune response that continues to cause frequent and often severe symptoms for patients. The opportunity to potentially bring new treatments from my lab to my clinical practice of pulmonary medicine remains a driving motivation for my career. Pulmonary problems can be so debilitating – lung function and health are so closely tied to quality of life. Being able to help people breath better is very rewarding.
What avenues of research are you pursuing?
My research focus is in asthma and mechanisms of airway hyper-reactivity, which is the tendency for airways to contract abnormally to a stimulus. In particular, I’ve found that stimulation of a specific innate immune receptor, Toll-like receptor 7, rapidly causes the airways to dilate. This is a similar response to what you would see if you took a puff off an inhaler for asthma, although by a very different mechanism. This was very unexpected since Toll-like receptors are typically thought to cause airway inflammation in response to an infection. As it turns out, this dilating effect is unique to Toll-like receptor 7; no other innate immune receptor responds in this way. Toll-like receptor 7 causes airway dilation by producing nitric oxide, a well-known smooth muscle relaxant, but had never before been associated with Toll-like receptor signaling. We found that the dilating effect of TLR-7 doesn’t involve typical toll-like receptor signaling pathways. As is often the case, these findings raise many more questions about why this signaling pathway exists in the airways and how it relates to airway diseases like asthma.
As part of this work, I’ve looked at Toll-like receptor 7 in a variety of airway models of asthma, as well as in human airway tissue, to see if it has the potential to be used in as an inhaler or bronchodilator. Some of these results have already been published. This work owes a great debt of thanks to those who choose to donate their organs, as much of my human studies involved airway tissue samples from the Pacific Northwest Transplant Bank.
What are the next steps for your research?
Next steps include further evaluating the mechanism and characterization of the sites of Toll-like receptor 7 activation, particularly in human airways. For example, recently I found that Toll-like receptor 7 is expressed along the lungs’ nerves and that certain nerves produce nitric oxide in response to receptor activation. This raises the question of whether nerves are involved in the immune response and, on the flip side, it makes us question how much we really know about Toll-like receptors – do they have other functions besides just working as an immune receptor? Are they involved in nerve growth or perhaps the way nerves regulate themselves? We’re trying to answer those questions.
This research ties back to Drs. Jacoby and Fryer’s long-standing interest in airway nerves and how they regulate bronchoconstriction. In asthma, the nerves don’t function properly, which contributes to bronchoconstriction, shortness of breath and wheezing. Not only are nerves dysfunctional, but my colleagues here at OHSU have found that airway nerves change their structure in the presence of inflammation driven by, for example, eosinophils – white blood cells that are often present in large concentrations in the lungs of asthmatics. Understanding the causes and mechanisms that lead to airway dysfunction in asthma is the long-term goal of our work with the hope that we can then translate our findings into meaningful treatments that can improve patients’ quality of life.
Asthma remains a debilitating problem for many patients despite a variety of current treatment options. Long term, this can lead to irreversible lung disease, frequent hospitalizations and death. Furthermore, our more severe asthma patients suffer from the side effects of medications like prednisone. Given that the incidence of asthma has been rising for the past three to four decades, there has never been more urgent need for asthma research that may lead to new therapies.
What do you do when you’re not at work?
Like many Portlanders, I enjoy being outdoors, whether it’s camping, hiking, mountain biking or running. I have two daughters, five and two years old, and I get to run after them as well. I’m also a huge soccer fan (Timbers, London’s Arsenal Football Club) and an Arizona Wildcat through and through.