Why I Became a 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.
Undergraduate, graduate and post-doctoral trainees are welcome to apply. Please contact email@example.com for current opportunities.
- 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)
Selected Publications (Last 5 Years)
Lab trainees underlined.
- Gestational long-term hypoxia induces metabolomic reprogramming and phenotypic transformations in fetal sheep pulmonary arteries. Leslie E, Lopez V, Anti NAO, Alvarez R, Kafeero I, Welsh DG, Romero M, Kaushal S, Johnson CM, Bosviel R, Blaženović I, Song R, Brito A, Frano MR, Zhang L, Newman JW, Fiehn O, Wilson SM. Am J Physiol Lung Cell Mol Physiol. 2021; 320(5): L770-L784.
- Conceptualizing conduction as a pliant electrical response: impact of gap junctions and ion channels. Hald BO, Welsh DG. Am J Physiol Heart Circ Physiol. 2020; 319(6):H1276-H1289.
- Conceptualizing Conduction as a Pliant Vasomotor response: Impact of Ca2+ fluxes and Ca2+ Sensitization. Hald BO, Welsh DG. Am J Physiol Heart Circ Physiol. 2020. doi: 10.1152/ajpheart.00286.2020.
- A stepwise approach to resolving small ionic currents in vascular tissue. Sancho M, Hald BO, Welsh DG. Am J Physiol Heart Circ Physiol. 2020; 318(3):H632-H638.
- Intercellular Conduction Optimizes Arterial Network Function and Conserves Blood Flow Homeostasis During Cerebrovascular Challenges. Zechariah A, Tran CHT, Hald BO, Sandow SL, Sancho M, Kim MSM, Fabris S, Tuor UI, Gordon GRJ, Welsh DG. Arterioscler Thromb Vasc Biol. 2020; 40(3): 733-750.
- KIR channels in the microvasculature: Regulatory properties and the lipid-hemodynamic environment. Sancho M, Welsh DG. Curr Top Membr. 2020; 85: 227-259.
- Membrane Lipid-KIR2.x Channel Interactions Enable Hemodynamic Sensing in Cerebral Arteries. Sancho M, Fabris S, Hald BO, Brett SE, Sandow SL, Poepping TL, Welsh DG. Arterioscler Thromb Vasc Biol. 2019; 39(6): 1072-1087.
- An assessment of KIR channel function in human cerebral arteries. Sancho M, Gao Y, Hald BO, Yin H, Boulton M, Steven DA, MacDougall KW, Parrent AG, Pickering JG, Welsh DG. Am J Physiol Heart Circ Physiol. 2019; 316(4): H794-H800.
- Caveolae Link CaV3.2 Channels to BKCa-Mediated Feedback in Vascular Smooth Muscle. Hashad AM, Harraz OF, Brett SE, Romero M, Kassmann M, Puglisi JL, Wilson SM, Gollasch M, Welsh DG. Arterioscler Thromb Vasc Biol. 2018; 38(10): 2371-2381.
- Differential targeting and signalling of voltage-gated T-type Cav3.2 and L-type Cav1.2 channels to ryanodine receptors in mesenteric arteries. Fan G, Kaßmann M, Hashad AM, Welsh DG, Gollasch M. J Physiol. 2018; 596(20): 4863-4877.
- The Conducted Vasomotor Response: Function, Biophysical Basis, and Pharmacological Control. Welsh DG, Tran CHT, Hald BO, Sancho M. Annu Rev Pharmacol Toxicol. 2018; 58:391-410.
- KIR channels tune electrical communication in cerebral arteries. Sancho M, Samson NC, Hald BO, Hashad AM, Marrelli SP, Brett SE, Welsh DG. J Cereb Blood Flow Metab. 2017; 37(6): 2171-2184.
- Interplay among distinct Ca2+ conductances drives Ca2+ sparks/spontaneous transient outward currents in rat cerebral arteries. Hashad AM, Mazumdar N, Romero M, Nygren A, Bigdely-Shamloo K, Harraz OF, Puglisi JL, Vigmond EJ, Wilson SM, Welsh DG. J Physiol. 2017; 595(4): 1111-1126.
- Abnormal Lymphatic Channels Detected by T2-Weighted MR Imaging as a Substrate for Ventricular Arrhythmia in HCM. 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. JACC Cardiovasc Imaging. 2016; 9(11): 1354-1356.
Scientist, Robarts Research Institute
Phone: 519-931-5777 ext. 25330