Dr. Jeremy Simpson
Hon BSc - University of Guelph
PhD- Queens University
I use classical physiology combined with proteomic techniques to study cardio-respiratory physiology and pathophysiology in multiple areas.
Heart failure remains the predominant cause of premature death and long-term morbidity in western society. Cardiac hypertrophy (increase in cell size) develops in such conditions of chronic hemodynamic overload as hypertension and valvular disease. Although the initial hypertrophy is critical as a compensatory response, it eventually becomes maladaptive, leading to contractile dysfunction and myocyte apoptosis. Eventually, heart failure occurs. Thus, a major goal of our lab is to better understand how the heart initially adapts to hypertension before the development of contractile dysfunction and heart failure. We believe this will lead to a better understanding of why the heart begins to fail and will ultimately lead to new targets for the treatment of heart failure.
I am also interested in skeletal and cardiomyocyte cell signalling during normal and hypoxic conditions, both between the muscle cells and with other tissues in the body. My research combines cell culture techniques with cutting edge proteomic tools to identify novel cardiac protein hormones. I use different models to investigate their functional effects in vitro and in vivo.
While much is known about the development of exercise-induced fatigue of limb muscles, little is known about the proteomic alterations that occur during exercise that contribute to or compensate for contractile dysfunction. Interestingly, we have recently shown that skeletal myofilament proteins undergo specific and progressive modifications during the development of muscle fatigue. Current work is aimed at identifying key post-translational modifications of myofilament proteins that arise during the development of whole muscle dysfunction as a result of fatigue or ischemia and delineating their role(s) in contraction. We have identified several key myofilament proteins that are altered in animal models but are potentially involved in the development of fatigue in humans.
Allwood MA, Kinobe RT, Ballantyne L, Romanova N, Melo LG, Ward CA, Brunt KR, Simpson JA. Heme Oxygenase-1 Overexpression Exacerbates Heart Failure With Aging and Pressure Overload but is Protective Against Isoproterenol-Induced Cardiomyopathy in Mice. Vardiovasc. Pathol. 23(4):231-7, 2014.
Beaudoin MS, Snook LA, Arkell AM, Stefnason A, Wan Z, Simpson JA, Holloway GP, Wright DC. Novel Effects of Rosiglitazone on SMAD2 and SMAD3 Signaling in White Adipose Tissue of Diabetic Rats. Obesity (Silver Spring). 22(7):1632-42, 2014.
Beaudoin MS, Perry CG, Arkell A, Chabowski A, Simpson JA, Wright DC, Holloway GP. Impairments in Mitochondrial Palmitoyl-CoA Respiratory Kinetics that Precede the Development of Diabetic Cardiomyopathy are Prevented by Resveratrol in ZDF Rats. J. Physiol. 592(Pt 12):2519-33, 2014.
Simpson JA, Iscoe S. Hypoxia, Not Hypercapnia, Induces Cardiorespiratory Failure in Rats. Respir. Physiol. Neurobiol. 196C:56-62, 2014.
Murrant CL, Dodd JD, Foster AH, Inch KA, Muckle FR, Ruiz DA, Simpson JA, Scholl JH. Prostaglandins Induce Vasodilation of the Microvasculature During Muscle Contraction and Induce Vasodilation Independent of Adenosine. J. Physiol. 592(Pt 6):1267-81, 2014.
Beaudoin MS, Snook LA, Arkell AM, Simpson JA, Holloway GP, Wright DC. Resveratrol Supplementation Improves White Adipose Tissues Function in a Depot-Specific Manner in Zucker Diabetic Fatty Rats. Am. J. Phyisol. Regul. Integr. Comp. Physiol. 305(5):R542-51, 2013.
Minsuk K., Platt, M. Shibasaki, T., Quaggin, S., Backx, P.H., Seino, S., Simpson, J. A., and D. J. Drucker. GLP-1 Receptor Activation and Epac2 link Atrial Natriuretic Peptide Secretion to Control of Blood Pressure. Nature Med. 19(5): 567-75, 2013.
Chapman DW, Simpson J.A., Iscoe S, Robins T, Nosaka K. Changes in Serum Fast and Slow Skeletal Troponin I Concentration Following Maximal Eccentric Contractions. J. Sci. Med. Sport. 16(1):82-5, 2013.
Foster GE, Nakano J, Sheel AW, Simpson J.A., Road JD, Reid WD. Serum Skeletal Troponin I Following Inspiratory Threshold Loading in Healthy Young and Middle-Aged Men. Eur. J. Appl. Physiol. 112(10): 3547-58, 2012.
Tsimakouridze EV, Straume M, Podobed PS, Chin H, Lamarre J, Johnson R, Antenos M, Kirby GM, Mackay A, Huether P, Simpson J.A., Sole M, Gadal G, Martino TA. Chronomics of Pressure Overload-Induced Cardiac Hypertrophy in Mice Reveals Altered Day/Night Gene Expression and Biomarkers of Heart Disease. Chronobiology International 29 (7), 810-821, 2012.
Wu X, Yin J, Simpson J. A., Kim KH, Gu S, Hong JH, Bayliss P, Backx PH, Neel BG, Araki T. Increased BRAF Heterodimerization is the Common Pathogenic Mechanism for Noonan Syndrome-Associated RAF1 Mutants. Mol. Cell. Biol. 32(19):3872-90, 2012.
Published with Commentary - Prostaglandin E2 in Remote Control of Myocardial Remodeling Sun H, Wang Y. Circulation. 2012 Jun 12;125(23):2818-20.)
Degousee N, Simpson J. A., Fazel S, Scholich K, Angoulvant D, Angioni C, Schmidt H, Korotkova M, Stefanski E, Wang XH, Lindsay TF, Ofek E, Pierre S, Butany J, Jakobsson PJ, Keating A, Li RK, Nahrendorf M, Geisslinger G, Backx PH, Rubin BB. Lack of Microsomal Prostaglandin E(2) Synthase-1 in Bone Marrow-Derived Myeloid Cells Impairs Left Ventricular Function and Increases Mortality After Acute Myocardial Infarction. Circulation. 2012 Jun 12;125(23):2904-13. Epub 2012 May 15.
Beca, S., Helli, P.B., Simpson, J.A., Peter, J., Chen, W.S.R., Conti, M., Backx, P.H. Loss of Phosphodiesterase 4D (PDE4D) Enhances Sarcoplasmic Reticulum Ca2+ Release and Cardiac Function, Independent of L-type Ca2+ Current. Circ. Res. Oct 14;109(9):1024-30.
Published with Commentary - RAS Signaling Pathway Mutations and Hypertrophic Cardiomyopathy: Getting Into and Out of the Thick of It. B.D. Gelb and M. Tartaglia. J. Clin. Invest. 121: 844-847, 2011.
Xue W, Simpson, J.A., , Hong, J., Kim, H., Thavarajah, N.K., Backx, P.H., Neel, B.G., Araki, T. MEK-ERK Pathway Modulation Ameliorates Disease Phenotypes in a Mouse Model of Noonan Syndrome Associated with the Raf1(L613V) Mutation. J. Clin. Invest. 121:1009-25,2011.
|Edgett, B.||Post-Doctoral Fellow|
|Herrera, S.||MSc Student|
|Holjak, E.||MSc Student|
|Marrow, J.||PhD Student|
|Mofford, J.||MSc Student|
|Ogilvie, L||PhD Student|
|Romanova, N.||Research Associate|
|Savinova, I||MSc Student|