Donald Welsh, Scientist
I have always been innately interested in physiology. As a high school athlete, I was naturally drawn to the function of the human body and this propelled me to study kinesiology as an undergraduate student. Perhaps the defining moment was an upper undergraduate course where I realized that those memorized signaling pathways were actually encoding biological functions I could tangibly see. This was revelational and immensely exciting. This excitement pushed me toward graduate studies and postdoctoral training in vascular biology. My career has been facilitate by wonderful mentors including Dr. Steven Segal (University of Missouri), and Drs. Mark Nelson and Joe Brayden (University of Vermont). Their enthusiasm was infectious and I was constantly reminded that academic scientists get paid to “think” and “do cool stuff”. Why would you want to do anything else?
My interests center on the contractile basis of vascular smooth muscle, with a primary focus in the cerebral circulation. As a trained electrophysiologist, I’m particularly interested in ion channels and the basis of electrical communication in the arterial wall. In regards to ion channels, current work focuses on the elusive T-type channels and ascertaining their biological function in both animal and human vessels. Understanding electrical communication has been a passion and over the past 15 years we have played a key role in defining the factors driving this biological process. We are beginning to translate this foundational work and in the process developing a better understanding of blood flow control and tissue injury following stroke. My research incorporates a broad array of techniques including molecular biology, immunohistochemistry, patch clamp electrophysiology, computer modeling, vessel myography and in vivo imaging.
Resistance arteries control the magnitude and distribution of tissue blood flow and these hollow organs are comprised of two key cell types. They include the smooth muscle cells that actively contract and the endothelial cells which line the interior of the blood vessel wall. My research focuses on the basis of vessel contractility and how ion channels and gap junctions (intercellular pores) control the electrical activity of smooth muscle/endothelial cells. We explore the basis of arterial contractility in both animals and humans using techniques that span from cells to whole organisms. They include:
- Patch clamp electrophysiology to assess ion channel activity.
- Western blotting to measure protein phosphorylation.
- Confocal microscopy to ascertain Ca 2+ dynamics/protein localization.
- Electron microscopy to visualize cellular ultrastructure.
- Pressure myography to measure arterial tone.
- Computational modeling to quantitatively assess charge movement and Ca 2+ dynamics.
My laboratory is currently funded by The Canadian Institutes of Health Research (CIHR) and the Natural Science and Engineering Research Council of Canada. We pursue a range of engaging questions, many focused on brain vasculature and the basis of blood flow control in health and disease. They include:
- Determining how mechanical forces are sensed by smooth muscle cells, change electrical activity and enable intravascular pressure to induce myogenic tone.
- Ascertaining how Ca 2+ channels on the plasma membrane (L- and T-type) and the sarcoplasmic reticulum (ryanodine and IP3 -receptors) govern arterial constriction.
- Defining the nature of electrical and second messenger communication among smooth muscle and/or endothelial cells.
My laboratory is currently seeking graduate students and post-doctoral scholars for projects in the area of cell-cell communication in the cerebrovasculature. Please apply directly to: email@example.com.
Ph.D., University of Guelph, 1994
M.Sc., University of British Columbia, 1989
B.Sc., University of Calgary, 1987
Postdoctoral Fellow, Department of Pharmacology, University of Vermont, 1998-2001
Postdoctoral Fellowship, Medical Research Council of Canada, 1999-2000
Postdoctoral Fellowship, American Heart Association, 1996-1998
Postdoctoral Fellow, John B. Pierce Laboratory, Department of Celluar & Molecular Physiology, Yale University, 1994-1997
Cecil and Linda Rorabeck Chair in Molecular Neuroscience and Vascular Biology, 2015-
Senior Scholar, Alberta Heritage Foundation for Medical Research, 2006-2013
Canada Research Chair, Tier II, 2003-2013
Research Scholar, Alberta Heritage Foundation for Medical Research, 2001-2006
Research Scholar, Heart & Stroke Foundation of Canada, 2001-2006
New Investigator Award, American Physiological Society, 2004
MacDonald Scholarship, Heart & Stroke Foundation of Canada, 2001-2002
Lemaster K, Jackson D, Welsh DG, Brooks SD, Chantler PD, Frisbee JC. Altered distribution of adrenergic constrictor responses contributes to skeletal muscle perfusion abnormalities in metabolic syndrome. Microcirculation, Epub, 2017.
Maarouf N, Sancho M, Fürstenhaupt T, Tran CH, Welsh DG. Structural analysis of endothelial projections from mesenteric arteries. Microcirculation, EPub, 2016.
Hashad AM, Mazumdar N, Romero M, Nygren A, Bigdely-Shamloo K, Harraz OF, Vigmond EJ, Wilson SM, Welsh DG. Interplay among distinct Ca2+ conductances drives Ca2+ sparks/spontaneous transient outward currents in rat cerebral arteries. J. Physiology, EPub, 2016.
Sancho M, Samson NC, Hald BO, Hashad AM, Marrelli SP, Welsh DG. KIR channels tune electrical communication in cerebral arteries. J. Cerebral Blood Flow Metab. EPub, 2016.
Welsh DG. The Secret Life of Telomerase. Circulation Research 118:781-782, 2016.
Kolman L, Welsh DG, Vigmond E, Joncas SX, Stirrat J, Scholl D, Rajchl M, Tweedie E, Mikami Y, Lydell C, Howarth A, Yee R, White JA. Abnormal lymphatic channels detected by T2-weighted MRI. JACC: Cardiovascular Imaging. 9:1354-1357, 2016.
Mufti RE, Zechariah A, Sancho M, Mazumdar N, Brett SE, Welsh DG. Implications of aVb3 integrin signaling in the regulation of Ca2+ waves and myogenic tone in cerebral arteries. Atherosclerosis, Thrombosis and Vascular Biology. 35:2571-2781, 2015.
Wei R, Lunn S, Tran CHT, Murphy T, Sandow S, Welsh DG and Plane F. Activation of endothelial IKCa channels underlies NO-dependent myoendothelial feedback. Vascular Pharmacology 74:130-138, 2015.
Harraz OF, Brett SE, Zechariah A, Romero M, Puglisi JL, Wilson SM and Welsh DG. Genetic ablation of CaV3.2 channels enhances the aterial myogenic response by modulating the RyR- BKCa axis. Atherosclerosis, Thrombosis and Vascular Biology. 35:1843-1851, 2015.
Hald BO, Welsh DG, Holstein-Rathlou NH, Jacobsen JC. Origins of variation in conducted vasomotor responses. Pflugers Arch. 467:2055-2067, 2015.
Harraz OF, Visser F, Brett SE, Goldman D, Hashad AM, Zechariah A, Menon BK, Watson T, Starreveld Y, Welsh DG. Human CaV1.2/CaV3.x channels mediate divergent vasomotor responses in human cerebral arteries. J Gen Physiol. 145:405-18, 2015.
Sullivan MN, Gonzales AL, Bruhl A, Leo MD, Jaggar JH, Welsh DG and Earley S. TRPA1 mediates NADPH oxidase-dependent cerebral arterial dilation. Science Signaling. 8(358): doi:10.1126/scisignal.2005659, 2015.
Scientist, Robarts Research Institute
Phone: 519-931-5777 x25330