Scott Johnstone

Johnstone, Scott R.

Primary Appointment

Instructor of Research, Cardiovascular Medicine


  • PhD, Cell and Molecular Biology, Glasgow Caledonian University

Contact Information

409 Lane Road
Building MR4, Rm 6071
Charlottesville, Va 22908
Telephone: 434-924-2093
Fax: PO Box 801394

Research Disciplines

Molecular Physiology and Biological Physics

Research Interests

Translating molecular mechanisms into therapeutic targets

Research Description

Core research
Cardiovascular diseases account for 1:4 deaths. Despite significant improvements in the way in which we successfully treat patients, this still accounts for a significant mortality rate. My research focuses on understanding the molecular mechanisms that regulate normal vascular physiology and the pathophysiology of disease. Defining pathways involved in cardiovascular disease allows us to more effectively target these for therapeutic intervention.

Inflammation in vascular disease
The primary cause of cardiovascular disease is atherosclerosis, where a buildup of cellular material in the blood vessel walls blocks blood flow. Atherosclerosis is a chronic inflammatory disease, where a prolonged immune reaction results in a change in the composition of the blood vessel. This can lead to complications including thrombosis and stroke. Our research is focused on defining how inflammation is regulated by the cells of the blood vessels wall, and using this information to design the best avenues for future therapeutic intervention.

Proliferation in vascular disease
Blockages that reduce blood flow to tissues such as the heart and lower limbs are the greatest contributors to CVD, and can result in heart attacks or a requirement for amputations. Treating blocked arteries 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 side effect of each of these treatments, is that the cells in the blood vessels start to divide (proliferate). This increases the number of cells, and blocks the artery once again. Clinically, this can lead to stent-failure in around 25% of patients and is a significant risk factor. Our research aims to identify new pathways that specifically regulate this process, to help us understand the disease better and to aid the development of targeted therapeutics.

Connexin (Cx) proteins and gap junctions
Cells communicate in a vast array of ways. The primary source of direct cell-to-cell communication occurs through the gap junction channels comprised of connexin proteins. In particular Cx43, is widely associated with proliferative diseases and shows great promise as a therapeutic target. 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 also regulate cellular processes 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 target diseased cells. We aim to define the unique molecular pathways controlled by these proteins, and are currently developing a range of inhibitors which show promise in reducing cell proliferation. Our hope is that these inhibitors will be valuable for future development and translation to therapeutics.

Pannexin (Panx) channels
Identified in 2000, this new class of purine (e.g. ATP) release channels appear to have multiple functions such as regulating cell death (apoptosis), inflammation and blood vessel physiology. Our research pinpoints that pannexin channels allow for a diverse array of signaling events within the vasculature, controlling aspects from blood vessel tone to inflammation. However, signaling regulation via these channels is still poorly understood. Our lab aims to define new molecular signaling pathways regulated by this class of membrane proteins. Our goal is to understand how these proteins are regulated from transcription to translation, and to identify channel functions that control to vascular physiology and pathophysiology.

Selected Publications