Stephen Archer, M.D.

Pulmonary Hypertension, Echocardiography and General Cardiology (with a Special Interest in Aortic Valve Disease).

Research Summary

Dr. Archer is an eminent clinical cardiologist and translational vascular biologist who studies mechanisms of oxygen sensing and develops experimental therapies for human diseases, including pulmonary arterial hypertension, persistent ductus arteriosus and cancer. An author of four books, Dr. Archer has also published over 170 peer-reviewed papers. He is on the editorial board of Circulation Research.  Dr. Archer’s Translational Cardiovascular Research Program strives for “Bench-Bedside” solutions for persistent ductus arteriosus, a common form of congenital heart disease, and pulmonary arterial hypertension, a fatal illness of young adults. His program explores the molecular basis for oxygen-sensing in two important blood vessels, the ductus arteriosus and pulmonary artery. Both arteries have similar, integrated O2-sensing systems that control vascular tone, consisting of a mitochondrial redox sensor, a diffusible mediator and an electrical effector (potassium and calcium channels). Dr. Archer and colleagues (Drs. Ken Weir-Minneapolis VAMC, and Evangelos Michelakis-University of Alberta, and Bernard Thébaud-University of Alberta) have made seminal contributions to understanding the mechanisms of hypoxic pulmonary vasoconstriction and oxygen-induced constriction of the ductus arteriosus. Dr. Archer also discovered a major mechanism of nitric oxide-induced vasorelaxation (activation of potassium channels).  With Dr. Michelakis, he translated this basic science observation into a new treatment for pulmonary arterial hypertension in humans (oral sildenafil). They also patented the use of dichloroacetate, an oral pyruvate dehydrogenase kinase inhibitor, as a potential treatment for several human cancers. His research is funded by NIH, CIHR, H&SF of Canada and CFI.

Selected Papers

*Bonnet, S., Archer, S.L., Allalunis-Turner, J., Haromy, A., Beaulieu, C., Thompson, R., Lee, C.T., Lopaschuk, G.D., Puttagunta, L., Harry, G., et al. 2007. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 11:37-51.

*Bonnet S., Michelakis ED, Porter CJ, Andrade-Navarro MA, Thebaud B, Bonnet S, Haromy A, Harry G, Mouudgil R., McMurtry MS, Weir EK, Archer S.L. An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension. Circulation. June 6 2006; 113(22):2630-2641.

Weir EK, Lopez-Barneo J, Buckler KJ, Archer S.L. Acute oxygen-sensing mechanisms. N Engl J Med 2005. 353:19:42-55.

*Bernard Thébaud, MD, PhD; Evangelos D. Michelakis, MD; Xi-Chen Wu, PhD; Rohit Moudgil, MSc; Michael Kuzyk, PhD; Jason R. B. Dyck, PhD; Gwyneth Harry, Msc; Kyoko Hashimoto, BSc; Alois Haromy, BSc; Ivan Rebeyka, MD; Archer S.L. Oxygen-sensitive Kv channel gene transfer confers oxygen-responsiveness to preterm rabbit and remodeled human ductus arteriosus: implications for infants with patent ductus arteriosus. Circulation 2004;110(11):1372-9.

Michelakis ED, Tymchak W, Noga M, Webster L, Wu X-C, Lien D, Wang SH, Modry, D, Archer S.L. Long-Term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Circulation 2003; 108: 2066-2069.

Michelakis ED, Rebeyka I, Wu X, Nsair A, Thebaud B, Hashimoto K, Dyck J, Haromy A, Harry G, Barr A, Archer S.L. 02 sensing in the human ductus arteriosus: Regulation of voltage-gated K+ channels in smooth muscle cells by a mitochondrial redox sensor. Circ Res. 2002;91:478-486.

Michelakis ED, McMurtry MS, Wu X, Waite R, Hashimoto K, Hopkins T, Lopaschuk G, Puttagunta L, Archer S.L.  Dichloroacetate a metabolic modulator prevents and reverses chronic hypoxic pulmonary hypertension in rats: Role of increased expression and activity of voltage-gated potassium channels. Circulation 2002, Jan 15; 105(2): 244-50.

*Archer, S.L, Souil, E, Dinh-Xuan, AT, Schremmer, B, Mercier, J-C, El Yaagoubi, A, Nguyen-Huu, L, Reeve, HL, Hampl, V.   Molecular identification of the role of the voltage gated K+ channels, Kv1.5 and Kv2.1 in pulmonary vasoconstriction and control of resting membrane potential in rat pulmonary artery myocyte. JCI. 1998, 101 (11) 1-12.

*Tristani-Firouzi M, Reeve HL, Tolarova S, Weir EK, Archer S.L.  Oxygen-induced constriction of rabbit ductus arteriosus occurs via inhibition of a 4-aminopyridine-, voltage-sensitive potassium channel. J Clin Invest. 1996, 98:1959-1965.

Archer S.L, Huang JMC, Hampl V, Nelson DP, Shultz PJ, Weir EK:  Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K+ Channel by GMP-dependent protein kinase.  Proc Natl Acad Sci USA 1994, 91: 7583-7587.