John Ussher, PhD (Pharmacology)

Associate Professor, Faculty of Pharmacy & Pharmaceutical Sciences

Contact

Associate Professor, Faculty of Pharmacy & Pharmaceutical Sciences
Email
jussher@ualberta.ca

Overview

Research

Research Interests:

Understanding how alterations in energy metabolism contribute to obesity-related metabolic disorders including insulin resistance, type 2 diabetes, and cardiovascular disease. Ongoing research projects in the laboratory include:

1) Active investigation into how modulating ketone body metabolism in the skeletal muscle can protect against obesity-induced insulin resistance and the development of type 2 diabetes.

2) Understanding the mechanisms driving cardiac insulin resistance during obesity/type 2 diabetes, with a focus on insulin resistance of specific pathways of insulin signalling in the heart that cause heart failure in patients with obesity/type 2 diabetes.

3) Ongoing studies in the lab aim to identify how epigenetic alterations to genes implicated in the control of energy metabolism are passed on from obese pregnant mother to child that increase the risk for early onset obesity.


Experimental Techniques Routinely Used in the Lab:

1) Creation of tissue-specific gene knockout mice

2) High fat feeding models of obesity

3) Assessment of insulin resistance/sensitivity via oral and intraperitoneal glucose tolerance testing, as well as intraperitoneal insulin tolerance testing

4) Assessment of insulin signalling via Western blotting techniques

5) Real-time PCR

6) Animal studies of exercise training

7) Surgically-induced animal models of cardiovascular disease including heart attack (temporary left anterior descending coronary artery ligation) and heart failure (permanent left anterior descending coronary artery ligation)

8) Assessment of heart function in animals via ultrasound echocardiography imaging

9) Assessment of flux through metabolic pathways (e.g. glucose oxidation, fatty acid oxidation, ketone body oxidation, glycolysis) in both isolated tissue and cell culture systems

10) Culturing of cardiac and skeletal muscle myocytes

11) Enzyme activity assays



Teaching

PHARM 573 - Lectures pertaining to the use of genetically modified mouse models in pharmaceutical sciences research

PHARM477 - Lectures pertaining to the pharmacotherapies for malaria

Announcements

 

Courses

PHARM 233 - Introduction to Pharmacology 2

Building on pharmacology fundamentals introduced in Pharm 203, students will continue learning fundamental principles of pharmacology that affect other organ systems, as well as core concepts on the mechanisms of action for drugs including those used in the treatment of various diseases. Special topics in pharmacology will also be covered. (Restricted to Pharmacy students.)

Winter Term 2021
PHARM 697A - Graduate Seminar

Seminar training and short seminar presentations on topics related to the student's field of research. Normally, the seminar will be presented during the student's second or third term. Required of all MSc and PhD students.

Fall Term 2020
PHARM 697B - Graduate Seminar

Seminar training and short seminar presentations on topics related to the student's field of research. Normally, the seminar will be presented during the student's second or third term. Required of all MSc and PhD students.

Winter Term 2021

Browse more courses taught by John Ussher

Publications

Accumulation of ceramide in slow-twitch muscle contributes to the development of insulin resistance in the obese JCR:LA-cp rat2.
Author(s): Fillmore, N., Keung, W., Kelly, S.E., Proctor, S., Lopaschuk, G.D., Ussher, J.R.
Publication: Experimental Physiology

5’AMP activated protein kinase increases glucose uptake independent of GLUT4 translocation in cardiac myocytes.
Author(s): Lee, C.T., Ussher, J.R., Mohammad, A., Lam, A., Lopaschuk, G.D.
Publication: Canadian Journal of Physiology and Pharmacology
Volume: 92
Issue: 4
Page Numbers: 307-314

Treatment with the 3-ketoacyl-CoA thiolase inhibitor trimetazidine does not exacerbate whole body insulin resistance in obese mice.
Author(s): Ussher, J.R., Keung, W., Fillmore N., Koves, T.R., Mori, J., Zhang, L., Lopaschuk, D.G., Ilkayeva, O.R., Wagg, C.S., Jaswal, J.S., Muoio, D.M., Lopaschuk, G.D.
Publication: Journal of Pharmacology and Experimental Therapeutics
Volume: 349
Issue: 3
Page Numbers: 487-496

The role of cardiac lipotoxicity in the pathogenesis of diabetic cardiomyopathy.
Author(s): Ussher, J.R.
Publication: Expert Reviews of Cardiovascular Therapy
Volume: 12
Issue: 3
Page Numbers: 345-358

Failing mouse hearts utilize energy inefficiently and benefit from improved coupling of glycolysis and glucose oxidation.
Author(s): Masoud, W.G.T., Ussher, J.R., Wang, W., Jaswal, J.S., Wagg, C.S., Dyck, J.R.B., Lygate, C.A., Neubauer, S., Clanachan, A.S., Lopaschuk, G.D.
Publication: Cardiovascular Research
Volume: 101
Issue: 1
Page Numbers: 30-38

Gut microbiota metabolism of L-carnitine and cardiovascular risk.
Author(s): Ussher, J.R., Lopaschuk, G.D., Arduini, A.
Publication: Atherosclerosis
Volume: 231
Issue: 2
Page Numbers: 456-461

Inhibition of fatty acid oxidation as an approach to treat diastolic heart failure.
Author(s): Ussher, J.R., Jaswal, J.S.
Publication: Heart and Metabolism
Volume: 61
Page Numbers: 20-24

Cardiac insulin resistance and decreased mitochondrial energy production precede the development of systolic heart failure following pressure overload hypertrophy.
Author(s): Zhang, L., Jaswal, J.S., Ussher, J.R., Sankaralingam, S., Wagg, C.S., Zaugg, M., Lopaschuk, G.D.
Publication: Circulation Heart Failure
Volume: 6
Issue: 5
Page Numbers: 1039-1048

Cardiac Insulin Resistance: It’s Sweeter Than You Think.
Author(s): Ussher, J.R., Lopaschuk, G.D.
Publication: Endocrinology
Volume: 154
Issue: 8
Page Numbers: 2575-2578

Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice.
Author(s): Keung, W., Ussher, J.R., Jaswal, J.S., Raubenheimer, M., Lam, V.H., Wagg, C.S., Lopaschuk, G.D.
Publication: Diabetes
Volume: 62
Issue: 3
Page Numbers: 711-720

Differentiating diastolic dysfunction from classic heart failure.
Author(s): Jaswal, J.S., Ussher, J.R.
Publication: Heart and Metabolism
Volume: 57
Page Numbers: 4-7

Targeting microRNAs to reduce cardiac lipotoxicity.
Author(s): Lopaschuk, G.D., Ussher, J.R.
Publication: Circulation Research
Volume: 116
Issue: 2
Page Numbers: 229-231

Inactivation of malonyl CoA decarboxylase reduces the inflammatory response associated with insulin resistance.
Author(s): Samokhvalov, V., Ussher, J.R., Fillmore N., Armstrong, I.K.G., Keung, W., Moroz, D., Lopaschuk, D.G., Seubert, J., Lopaschuk, G.D.
Publication: American Journal of Physiology: Endocrinology and Metabolism
Volume: 303
Issue: 12
Page Numbers: E1459-E1468

The impact of current and novel anti-diabetic therapies on cardiovascular risk.
Author(s): Ussher, J.R., Sutendra, G., Jaswal, J.S.
Publication: Future Cardiology
Volume: 8
Issue: 6
Page Numbers: 895-912

Something Old Holds Potential to be Something New in Heart Failure: Allopurinol Revisited.
Author(s): Jaswal, J.S., Ussher, J.R., Lopaschuk, G.D, Johnstone, D.E.
Publication: Canadian Journal of Cardiology
Volume: 28
Issue: 6
Page Numbers: 626-628

Effects of performance enhancing drugs on cardiac structure and energy substrate metabolism.
Author(s): Ussher, J.R., Jaswal, J.S.
Publication: Heart and Metabolism
Volume: 56
Page Numbers: 34-37

Pyridine Nucleotide Regulation of Cardiac Intermediary Metabolism.
Author(s): Ussher, J.R., Jaswal, J.S., Lopaschuk, G.D.
Publication: Circulation Research
Volume: 111
Issue: 5
Page Numbers: 628-641

Inhibition Of Serine Palmitoyl Transferase I Reduces Cardiac Ceramide Levels And Increases Glycolysis Rates Following Diet-Induced Insulin Resistance.
Author(s): Ussher, J.R., Folmes, C.D.L., Keung, W., Fillmore N., Jaswal, J.S., Cadete, V.J.J., Beker, D.L., Lam, V.H., Zhang, L., Lopaschuk, G.D.
Publication: PLoS ONE
Volume: 7
Issue: 5
Page Numbers: e37703

An ACE Up Your Sleeve: 2 Is Better Than 1.
Author(s): Ussher, J.R., Lopaschuk, G.D.
Publication: Circulation Research
Volume: 110
Issue: 10
Page Numbers: 1270-1272

Stimulation of glucose oxidation protects against acute myocardial infarction and reperfusion injury.
Author(s): Ussher, J.R., Wang, W., Gandhi, M., Keung, W., Samokhvalov, V., Oka, T., Wagg, C.S., Jaswal, J.S., Harris, R.A., Clanachan A.S., Dyck, J.R.B., Lopaschuk, G.D.
Publication: Cardiovascular Research
Volume: 94
Issue: 2
Page Numbers: 359-369

Cardiac hypertrophy in the newborn delays the maturation of fatty acid β-oxidation and compromises post-ischemic functional recovery.
Author(s): Oka, T., Lam, V.H., Zhang L., Keung, W., Cadete, V.J.J, Samokhvalov, V., Tanner B.A., Beker, D.L., Ussher, J.R., Huqi, A., Jaswal, J.S., Rebeyka, I.M., Lopaschuk, G.D.
Publication: American Journal of Physiology: Heart and Circulatory Physiology
Volume: 302
Issue: 9
Page Numbers: H1784-H1794

Cardiovascular Biology of the Incretin System.
Author(s): Ussher, J.R., Drucker, D.J.
Publication: Endocrine Reviews
Volume: 33
Issue: 2
Page Numbers: 187-215

Cardiomyocyte glucagon receptor signaling modulates outcomes in mice with experimental myocardial infarction.
Author(s): Ali, S., Ussher, J.R., Baggio, L.L., Kabir, M.G., Charron, M.J., Ilkayeva, O.R., Newgard, C.B., Drucker, D.J.
Publication: Molecular Metabolism
Volume: 4
Issue: 2
Page Numbers: 132-143

The Gipr is Essential for Adrenocortical Steroidogenesis However Corticosterone Deficiency Does Not Mediate the Favourable Metabolic Phenotype of Gipr-/- Mice.
Author(s): Bates, H.E., Campbell, J.E., Ussher, J.R., Baggio, L.L., Maida, A.M., Seino, Y., Drucker, D.J.
Publication: Diabetes
Volume: 61
Issue: 1
Page Numbers: 40-48

Targeting fatty acid and carbohydrate oxidation – a novel therapeutic intervention in the ischemic and failing heart.
Author(s): Jaswal, J.S., Keung, W., Wang, W., Ussher, J.R., Lopaschuk, G.D.
Publication: Biochimica et Biophysica Acta
Volume: 1813
Issue: 7
Page Numbers: 1333-1350

Cardiac diacylglycerol accumulation in high fat-fed mice is associated with impaired insulin-stimulated glucose oxidation.
Author(s): Zhang, L., Ussher, J.R., Oka, T., Cadete, V.J., Wagg, C.S., Lopaschuk, G.D.
Publication: Cardiovascular Research
Volume: 89
Issue: 1
Page Numbers: 148-156

Inhibition of De Novo Ceramide Synthesis Reverses Diet-Induced Insulin Resistance and Enhances Whole Body Oxygen Consumption.
Author(s): Ussher, J.R., Koves, T.R., Cadete, V.J.J., Zhang, L., Jaswal, J.S., Swyrd, S.J., Lopaschuk, D.G., Proctor, S.D., Keung, W., Muoio, D.M., Lopaschuk, G.D.
Publication: Diabetes
Volume: 59
Issue: 10
Page Numbers: 2453-2464

Targeting Intermediary Metabolism in the Hypothalamus as a Mechanism to Regulate Appetite.
Author(s): Lopaschuk, G.D., Ussher, J.R., Jaswal, J.S.
Publication: Pharmacological Reviews
Volume: 62
Issue: 2
Page Numbers: 237-264

Myocardial Fatty Acid Metabolism in Health and Disease.
Author(s): Lopaschuk, G.D., Ussher, J.R., Folmes, C.D.L., Jaswal, J.S., Stanley, W.C.
Publication: Physiological Reviews
Volume: 90
Issue: 1
Page Numbers: 207-258

Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function.
Author(s): Basu, R., Oudit, G.Y., Wang, X., Zhang, L., Ussher, J.R., Lopaschuk, G.D., Kassiri, Z.
Publication: American Journal of Physiology: Heart and Circulatory Physiology
Volume: 297
Issue: 6
Page Numbers: H2096-H2108

The role of the atypical protein kinase C zeta in the regulation of 5’AMP activated protein kinase in cardiac and skeletal muscle.
Author(s): Ussher, J.R., Jaswal, J.S., Wagg, C.S., Armstrong, H.E., Lopaschuk, D.G., Keung, W., Lopaschuk, G.D.
Publication: American Journal of Physiology: Endocrinology and Metabolism
Volume: 297
Issue: 2
Page Numbers: E349-E357

Insulin-Stimulated Cardiac Glucose Oxidation is Increased in Hearts from High Fat Diet-Induced Obese Mice Lacking Malonyl CoA Decarboxylase.
Author(s): Ussher, J.R., Koves, T.R., Jaswal, J.S., Zhang, L., Ilkayeva, O., Dyck, J.R., Muoio, D.M., Lopaschuk, G.D.
Publication: Diabetes
Volume: 58
Issue: 8
Page Numbers: 1766-1775

Myocardial fatty acid utilization as a determinant of cardiac efficiency and function.
Author(s): Jaswal, J.S., Ussher, J.R., Lopaschuk, G.D.
Publication: Clinical Lipidology
Volume: 4
Issue: 3
Page Numbers: 379-389

MicroRNAs as therapeutics for heart disease.
Author(s): Ussher, J.R.
Publication: Heart and Metabolism
Volume: 65
Page Numbers: 37-39

Targeting malonyl CoA inhibition of mitochondrial fatty acid uptake as an approach to treat cardiac ischemia.
Author(s): Ussher, J.R., Lopaschuk, G.D.
Publication: Basic Research in Cardiology
Volume: 104
Issue: 2
Page Numbers: 203-210

The malonyl CoA Axis as a potential target for the treatment of ischemic heart disease.
Author(s): Ussher, J.R., Lopaschuk, G.D.
Publication: Cardiovascular Research.
Volume: 79
Issue: 2
Page Numbers: 259-268

Entry exclusion in the IncHI1 plasmid R27 is mediated by EexA and EexB.
Author(s): Gunton, J.E., Ussher, J.E.R., Rooker, M.M., Wetsch N.M., Alonso, G., Taylor, D.E.
Publication: Plasmid
Volume: 59
Issue: 2
Page Numbers: 86-101

Mitochondrial Overload and Incomplete Fatty Acid Oxidation Contribute to Skeletal Muscle Insulin Resistance.
Author(s): Koves, T.R., Ussher, J.R., Slentz, D., Mosedale, M., Ilkayeva, O., Bain, J., Stevens, R., Dyck, J., Newgard, C.B., Lopaschuk, G., Muoio D.M.
Publication: Cell Metabolism
Volume: 7
Issue: 1
Page Numbers: 45-56

Clinical implications of energetic problems in cardiovascular disease.
Author(s): Ussher, J.R., Lopaschuk, G.D.
Publication: Heart and Metabolism
Volume: 32
Page Numbers: 9-17

Sweet as sugar: Excessive glucose metabolism in the failing heart.
Author(s): Ussher, J.R.
Publication: Future Cardiology
Volume: 10
Issue: 4
Page Numbers: 465-468

Deciphering ventricular GLP-1 action: time for a change of heart.
Author(s): Ussher, J.R.
Publication: American Journal of Physiology: Heart and Circulatory Physiology
Volume: 307
Issue: 10
Page Numbers: H1390-H1392

Trimetazidine therapy prevents obesity-induced cardiomyopathy in mice.
Author(s): Ussher, J.R., Fillmore, N., Keung, W., Mori, J., Beker, D.L., Wagg, C.S., Jaswal, J.S., Lopaschuk, G.D.
Publication: Canadian Journal of Cardiology
Volume: 30
Issue: 8
Page Numbers: 940-944

Inactivation of the cardiomyocyte glucagon-like peptide-1 receptor (GLP-1R) unmasks cardiomyocyte-independent GLP-1R-mediated cardioprotection.
Author(s): Ussher, J.R., Baggio, L.L., Campbell, J.E., Mulvihill, E.E., Kim, M.S., Kabir, M.G., Cao, X., Baranek, J., Stoffers, D.A., Seeley, R.J., Drucker, D.J.
Publication: Molecular Metabolism
Volume: 3
Issue: 5
Page Numbers: 507-517

Cardiovascular actions of incretin-based therapies.
Author(s): Ussher, J.R., Drucker, D.J.
Publication: Circulation Research
Volume: 114
Issue: 11
Page Numbers: 1788-1803