Clinical Assistant Professor
Research Summary:

The cross-application of techniques from cardiovascular physiology and immunology has resulted in exciting discoveries, including proving for the first time that stimulation of Toll-Like Receptors expressed by cardiac myocytes resulted in cardiac contractile dysfunction. Looking farther into the cardiac cell in inflammatory heart disease, two proteins previously unknown in the heart (S100A8 and S100A9) are responsible for altered cardiac physiology in response to infection. These two proteins bind the RAGE receptor, resulting in decreased calcium flux and cardiac contractility. The RAGE receptor has recently been found to highly regulate cardiac function and is known to impair cardiac contractility when exposed to highly glycosylated proteins such as those seen in diabetics. The autocrine pathway resulting form molecular products of Toll-Like receptor stimulation in cardiac myocytes represents an exciting potential common inflammatory pathway involving acute infection, inflammation and diabetes.

University of Western Ontario Chemistry, MD University of Western Ontario, BSc
Recent Publications:

•John Boyd, Edmond Chau, Delbert Dorscheid, Gurpreet K Singhera, Ehsan Davani, Anna Meredith, Keith Walley and Yingjing Wang. “Cardiac ICAM-1 mediates leukocyte-dependent decreased ventricular contractility in endotoxemic mice.” CARDIOVASCULAR RESEARCH. 72.1 (Oct 1, 2006): 134-142.
•John Boyd, Maziar Divangahi, Linda Yahiaoui, Dusanka Gvozdic, Salman Qureshi and Basil Petrof. “Toll-like receptors differentially regulate CC and CXC chemokines in skeletal muscle via NF-kappaB and calcineurin”. INFECTION AND IMMUNITY. 74.12 (Dec, 2006) 74(12):6829-6838.
•John Boyd, Sumeet Mathur, Yingjin Wang, Ryon Bateman and Keith Walley. “Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-kappaB dependent inflammatory response”. Cardiovascular Research 72.3 (Dec 1, 2006): 384-393.
•Chiho Tokunga, Ryon Bateman, John Boyd, Yingjin Wang, James Russell and Keith  Walley. “Albumin resuscitation improves ventricular contractility and myocardial tissue oxygenation in rat endotoxemia: Critical Care Medicine 35.5 (May, 2007): 1341-1347.
•J Boyd, EC Chau, C Tokunaga, G Halijan, EY Davani, Y Wang, KR Walley. Fibrinogen decreases cardiomyocyte contractility through an ICAM-1 dependent mechanism. Critical Care. 12.1 (Jan 3, 2008).
•Boyd, John H, Bernard Kan, Yingjin Wang, Haley Robert and Keith R Walley. “S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation end products”. CIRCULATION RESEARCH. (Apr 10, 2008).
•Boyd JH and Keith R Walley. ‘Is there a role for sodium bicarbonate in treating lactic acidosis from shock?’ Current Opinion In Critical Care  (Aug 14, 2008) (4):379-83.
•Boyd JH, Cheryl Holmes, Yingjing Wang, Haley Robert and Keith R Walley. ‘Vasopressin decreases sepsis-induced pulmonary inflammation through the V2R’. Resuscitation 2008 Nov; 79(2):325-31.
•Inrambarya T, Boyd JH, Wang Y, Walley KR. Low-dose vasopressin infusion results in increased mortality and cardiac dysfunction following ischemia-reperfusion. Critical Care. 2009 Jun 23; 13(3):R98.
•Nakada E, Walley KR, vonDaedelson p and Boyd JH. Toll-like receptor-3 stimulation upregulates sFLT-1 production by trophoblast cells. Placenta. 2009 Sep; 30(9):774-9.
•Labbe K, Danialou G, Gvozdic D, Demoule A, Divangahi M, Boyd JH, Petrof BJ. Inhibition of monocyte chemoattractant protein-1 prevents diaphragmatic inflammation and maintains contractile function during endotoxemia. Crit Care. 14(5):R187, 2010.
•Marchant DJ, Singhera GK, Utokaparch S, Hackett TL, Boyd JH, Luo Z, Si X, Dorscheid DR, McManus BM, Hegele RG. Toll like receptor 4 mediated p38 mitogen activated protein kinase activation is a determinant of respiratory virus entry and tropism. J  Virol. 121(24):2609-2611, 2010.
•Nakada TA, Russell JA, Boyd JH, Aguirre-Hernandez R, Thain KR, Thair SA, Nakada E, McConechy M, Walley KR. β2-Adrenergic receptor gene polymorphism is associated with mortality in septic shock.  Am J Respir Crit Care Med. 181(2):143-149, 2010.
•Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscitation in septic shock: A positive fluid balance and elevated central venous pressure are associated with increased mortality. Critical Care Med. 2011 Feb;39(2):259-65.
•Thair SA, Walley KR, Nakada T, McConechy MK, Boyd JH, Russell JA. A single nucleotide polymorphism in NF-B inducing kinase is associated with mortality in septic shock. J Immunol. 2011 Feb 15;186(4):2321-8.
•Nakada TA, Russell JA, Boyd JH, McLaughlin L, Nakada E, Thair SA, Hirasawa H, Oda S, Walley KR. Association of angiotensin II type 1 receptor-associated protein (AGTRAP) gene polymorphism with increased mortality in septic shock. Crit Care Med. 2011 Mar 17.
•Nakada T, Russell JA, Wellman H, Boyd JH, Nakada E, Thain KR, Thair SA, Hirasawa H, Oda S, Walley KR. Leucyl/cystinyl aminopeptidase (LNPEP) gene variants in septic shock. Chest. 2011 May;139(5):1042-9.