Led by principal investigator Scott Johnstone, Ph.D., focuses on understanding how healthy blood vessels are altered in disease and defining effective pathways to therapeutically target vascular disease. Cardiovascular disease affects over a third of Americans, causing approximately 2,200 deaths per day. In the U.S., 50 percent of cardiovascular disease patients are less than 60 years old, resulting in a need to effectively treat patients for many years to maintain vascular health.
Inflammation in vascular disease
The primary cause of cardiovascular disease is a chronic inflammatory disease called atherosclerosis. Inflammation changes the cellular composition of the blood vessel wall, essentially caused by a buildup of cellular material, which blocks blood flow. This can lead to major adverse complications including thrombosis, stroke and death. Cell signaling is a key regulator of the inflammatory process within the blood vessels. The Johnstone Lab's research focuses on the identification of cell signaling pathways that could provide a better understanding of the underlying causes of cardiovascular disease.
Proliferation in vascular disease
Treating arterial blockages in patients involves either grafting of blood vessels to bypass the blockage (coronary artery bypass) or implanting support structures called “stents” in the vessel to open up the blood flow. A significant side effect of each of these treatments is that cells start to divide inside the blood vessel wall, blocking the artery once again. The lab's research aims to identify new pathways that specifically regulate this process to help us understand the disease and to allow for the development of targeted therapeutics.
Connexin proteins, gap junctions and therapeutics
Cells communicate in a vast array of ways. The primary source of direct cell-to-cell communication occurs through gap junction channels comprised of connexin proteins. In addition to their well-established role in coordinating tissue functions, research by our group and others has shown that these are highly diverse proteins, which regulate cell functions through direct protein-protein interactions. Our lab focuses on identifying novel pathways involved in the formation of these interactions and ways in which we can manipulate these to disrupt diseased cell functions. Currently, the Johnstone Lab is developing a range of peptide-inhibitors which show promise in reducing cell proliferation in vivo and for future development to small molecules drugs.
Identified in 2000, this new class of purine (e.g. ATP) release channels have can control multiple cellular and tissue functions. Our research pinpoints that pannexin channels allow for a diverse array of signaling events within the vasculature, controlling normal physiological processes such as blood vessel tone to pathological vascular inflammation. However, signaling regulation via these channels is still poorly understood. The lab aims to define new molecular signaling pathways regulated by this class of membrane proteins. Its goal is to understand how these proteins are regulated from transcription to translation, and to identify channel functions in vascular physiology and pathophysiology.
There are common pathways in vascular disease, cancer and wound healing. These include the role for inflammation, cell signaling and cellular proliferation. Currently, the Johnstone Lab is working with multiple groups to investigate parallel pathways which can be exploited to reduce proliferation in cancer cells and to promote wound healing with reduced scar formation.