PH.D. University of Guelph
M.Sc. University of British Columbia
B.Sc. University of Calgary
Office: Robarts Research Institute, Room 4245C
p. 519.931.5777 x. 25330
See Publications by Don Welsh on PubMed
Current Research Interests:
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
- Pressure myography to measure arterial tone and membrane potential
- Western blotting to measure protein phosphorylation
- Confocal microscopy to ascertain Ca2+ dynamics/protein localization
- Multiphoton imaging of the cerebral vasculature
- Computational modeling to quantitatively assess charge movement and Ca2+ dynamics.
My laboratory is currently funded by the Canadian Institutes of Health Research, Canadian Foundation for Innovation, Heart and Stroke Foundation 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 such as pressure and flow are sensed by smooth muscle and endothelial cells, changing electrical activity and blood vessel 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.
- Determining of impact of vascular disease (dyslipidemia, hypertension) impact the activity and expression of ion channels.
We currently have positions available for PostDoctoral Scholars and graduate students. Contact me at dwelsh24 at uwo.ca for more information.
Recent Publications (from a total of 77; trainees underlined)
Hashad AM, Sancho M, Brett SE, Welsh DG. Reactive oxygen species mediate the suppression of arterial smooth muscle T-type Ca2+ channels by angiotensin II. Science Reports, 8(1):3445. doi: 10.1038/s41598-018-21899-5, 2018.
Gollasch M, Welsh DG, Schubert R. Perivascular adipose tissue and the dynamic regulation of Kv7 and Kir channels: Implications for resistant hypertension. Microcirculation, 25(1). doi: 10.1111/micc.12434, 2018.
Welsh DG, Tran CHT, Hald BO, Sancho M. The conducted vasomotor response: Biophysical basis and pharmacological control. Annual Reviews of Pharmacology & Toxicology, 58:391-410, 2018.
Welsh DG, Longden TA. Endothelial signaling and the dynamic regulation of arterial tone: A surreptitious relationship. Microcirculation, 24(3). doi: 10.1111/micc.12370, 2017.
Maarouf N, Sancho M, Fürstenhaupt T, Tran CH, Welsh DG. Structural analysis of endothelial projections from mesenteric arteries. Microcirculation, doi: 10.1111/micc.12330, 2017.
Hashad AM, Mazumdar N, Romero M, Nygren A, Bigdely-Shamloo K, Harraz OF, Puglisi JL, Vigmond EJ, Wilson SM, Welsh DG. Interplay among distinct Ca(2+) conductances drives Ca(2+) sparks/spontaneous transient outward currents in rat cerebral arteries. J Physiol. 595(4):1111-1126, 2017.
Sancho M, Samson NC, Hald BO, Hashad AM, Marrelli SP, Brett SE, Welsh DG. K(IR) channels tune electrical communication in cerebral arteries. J Cereb Blood Flow Metab. 37(6):2171-2184, 2017.
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 MR Imaging as a Substrate for Ventricular Arrhythmia in HCM. JACC Cardiovasc Imaging, 9(11):1354-1356, 2016.
Mufti RE, Zechariah A, Sancho M, Mazumdar N, Brett SE, Welsh DG. Implications of αvβ3 Integrin Signaling in the Regulation of Ca2+ Waves and Myogenic Tone in Cerebral Arteries. Arterioscler Thromb Vasc Biol., 35(12):2571-8, 2015.
Kerr PM, Wei R, Tam R, Sandow SL, Murphy TV, Ondrusova K, Lunn SE, Tran CHT, Welsh DG, Plane F. Activation of endothelial IKCa channels underlies NO-dependent myoendothelial feedback. Vascul Pharmacol., 74:130-138, 2015.
Harraz OF, Brett SE, Zechariah A, Romero M, Puglisi JL, Wilson SM, Welsh DG. Genetic ablation of CaV3.2 channels enhances the arterial myogenic response by modulating the RyR-BKCa axis. Arterioscler Thromb Vasc Biol., 35(8):1843-51, 2015.
Harraz OF, Visser F, Brett SE, Goldman D, Zechariah A, Hashad AM, Menon BK, Watson T, Starreveld Y, Welsh DG. CaV1.2/CaV3.x channels mediate divergent vasomotor responses in human cerebral arteries. Journal of General Physiology. 145:405-418, 2015.
Welsh DG. TRPV4 channel cooperativity in the resistance vasculature. Biophysical Journal. 108:1312-1313, 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. 6;8(358);ra2, 2015.
Hald BO, Welsh DG, Holsein-Rathlou NH, and Jacobsen JCB. Origins of variation in conducted vasomotor responses. Pflugers Arch. 467: 2055-2067, 2014.