Kathleen MacLeod
About the Principal Investigator
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Training
| Degree: | B.Sc. (Biochemistry) |
| Institution: | McGill University |
| Year: | 1974 |
| Degree: | Ph.D. (Pharmacology) |
| Institution: | University of Alberta |
| Year | 1978 |
Current Position
| Position: | Professor |
| Institution: | Division of Pharmacology |
Major Awards
| Name: | Scholarship |
| Organization: | Canadian Heart Foundation |
| Name: | Teaching Award |
| Organization: | Killam University |
About the Lab
Cardiovascular complications are the major problem for people with both type 1 and type 2 diabetes. Diabetic patients have a greater incidence of hypertension, congestive heart failure, atherosclerosis and circulatory disturbances than people without diabetes, and in addition develop a specific form of heart dysfunction called diabetic cardiomyopathy. My lab is interested in understanding the reasons for the greater cardiovascular dysfunction in diabetic patients, with the goal of identifying potential therapeutic targets. Changes in many cellular mechanisms have been identified in cardiovascular tissues in diabetes. Our goal is to identify changes in the intracellular signaling pathways that regulate cardiac and vascular contraction. To do so, our investigations range from the subcellular to the whole animal level, and encompass techniques including biochemical analysis, mass spectroscopy, electron, confocal and fluorescence microscopy, wire myography, and together with our collaborators, measurements of blood pressure (both indirect and direct) and cardiac function, at the level of myocytes, whole hearts and whole animals (echocardiography).
Training Environment
The training environment in my lab is designed to endow students with the fundamental skills they need to be successful in their research career. Cooperation between the members of my group enables the exchange of research skills between senior lab members and new students. The development of communication skills and integration of knowledge is encouraged through attending regular lab meetings where experimental results are presented and discussed. I work very closely with my students and offer them continuous guidance along the way. At the same time, I expect students in my lab to be committed to research, and to put effort in developing critical thinking and organizational skills and the ability to work independently.
Projects
Recently we have focused on the significance of activation of the RhoA/ROCK pathway in the contractile dysfunction associated with diabetic cardiomyopathy. We found that this pathway is activated in cardiomyocytes from a diabetic rat model, and surprising, that acute inhibition of ROCK improves contractile function of diabetic hearts both in vivo and in vitro. Our current research is directed towards understanding the underlying mechanisms contributing to increased activation of the pathway, and the ways in which over-activation of the pathway impairs cardiac contractility in diabetes.
In other work, we are studying in the consequences of diabetic-induced activation of protein kinase C, particularly PKCb2 in cardiovascular tissues. Increased activation of PKCb2 has been implicated in the cardiovascular complications of diabetes, but its downstream targets have not been well studied. We have found that this isoform of PKC is present in mitochondria from diabetic rat hearts, where it appears to modulate the activity of some mitochondrial proteins. We are currently identifying the mitochondrial targets of PKCb2 and the consequences of the changes in their activity to mitochondrial and cardiac function in diabetes.
Selected Publications
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