University of Vermont

College of Medicine

Department of Pharmacology

nelsonlab

Nelson Lab

Mark T. Nelson, Ph.D., University Distinguished Professor & Chair, Pharmacology

Mark T. Nelson, Ph.D.

University Distinguished Professor and Chair
Department of Pharmacology
Goggle Scholar Citations Profile

Contact Information:

Department of Pharmacology
The University of Vermont, College of Medicine
Given Building, Room B-333A
89 Beaumont Avenue
Burlington, VT 05405-0068
Email: mark.nelson@uvm.edu
Phone: (802) 656-2500
Fax: (802) 656-4523

Research Interests

The overall goal of the research in Dr. Nelson's laboratory is to understand the control of smooth muscle and endothelial cell function by ion channels and calcium signaling.

There are three major research areas in the lab:

  1. To understand the mechanisms by which computationally active neurons in the brain control local cerebral blood flow (CBF) ("neurovascular coupling"), using optical techniques to measure calcium signaling and arteriolar diameter in the neurovascular unit (neurons, astrocytes, arteriolar smooth muscle and endothelium) in brain slices as well as CBF in vivo, electrophysiological techniques to measure membrane currents and membrane potential of astrocytes, smooth muscle and endothelial cells from parenchymal arterioles. Arteriolar diameter is also measured in isolated pressurized parenchymal arterioles.
  2. To understand how sympathetic nerves, smooth muscle cells and endothelial cells communicate ("vascular crosstalk") to control the function of resistance-sized peripheral arteries.
  3. To understand the roles of ion channels and calcium signaling in the control of urinary bladder function in health and disease. Approaches cover the spectrum from molecular, cellular, intact tissue, whole organ and in vivo (local CBF, blood pressure, urodynamics). A number of genetic mouse models are used to unravel control mechanisms. Relevant ion channels in smooth muscle, endothelium and astrocytes are being explored, including voltage-dependent calcium channels, inward rectifier potassium channels, calcium-sensitive BK, IK, SK channels, voltage-dependent potassium channels, ATP-sensitive potassium channels, TRPV4 channels, ryanodine receptor channels, IP3R channels, and P2X1 receptor channels. The ultimate objections are to understand the basic mechanisms for ion channel control of local cerebral blood flow, peripheral resistance and urinary bladder function, and using this information to understand pathologies and possible new therapeutic interventions.

People in the Lab

Faculty and Research Scientists

Adrian Bonev, Ph.D., Fabrice Dabertrand, Ph.D., Thomas Heppner, Ph.D., Swapnil Sonkusare, Ph.D., David Hill-Eubanks, Ph.D.

 

Postdoctoral Associates and Fellows

Thomas Dalsgaard, Ph.D., Bud Etherton, Ph.D., Albert Gonzales, Ph.D.

Christel Joergensen, Ph.D., Thomas Longden, Ph.D., Nathan Tykocki, Ph.D.

Laboratory Research Technicians

Samantha O'Dwyer, Jessica Pearson, Theresa Wellman

Recent Publications

For a complete list of Mark T. Nelson's publications, please visit PubMed.

  1. Krishnamoorthy G, Sonkusare SK, Heppner TJ, Nelson MT.  Opposing roles of smooth muscle BK channels and ryanodine receptors in the regulation of nerve-evoked constriction of mesenteric resistance arteries. Am J Physiol Heart Circ Physiol.  2014 Feb 7. (Epub ahead of print)  PMID:  24508642
  2. Dunn KM, Nelson MT.  Neurovascular signaling in the brain and the pathological consequences of hypertension. Am J Physiol Heart Circ Physiol.  2013 Oct 25.  PMID:  24163077
  3. Cipolla MJ, Sweet JG, Gokina N, White S, Nelson MT.  (2013): Mechanisms of enhanced basal tone of brain parenchymal arterioles during early postischemic reperfusion: Role of ET-1 induced peroxynitrite generation. J Cerebr Blood Flow Metab.  2013 Jun 19.  Doi:  10.1038/jcbfm.2013.99.   PMID:  23778163
  4. Dunn KM, Hill-Eubanks DC, Liedtke WB, Nelson MT.  TRPV4 channels stimulate Ca2+ induced Ca2+ release in astrocytic endfeet and amplify neurovascular coupling responses.   Proc Natl Acad Sci USA.  2013 Apr 9; 110(15):  6157-6162.  Doi:  10.1073/pnas.  1216514110.  PMID:  23530219 
  5. Dabertrand F, Hannah RM, Pearson JM, Hill-Eubanks DC, Brayden JE, Nelson MT. Prostaglandin E(2), a postulated astrocyte-derived neurovascular coupling agent, constricts rather than dilates parenchymal arterioles.  J Cereb Blood Flow Metab.  2013 Feb 6.  10.1038/jcbfm.2013.9.  PMID:  23385200
  6. Dabertrand F, Nelson MT, Brayden JE.  Ryanodine receptors, calcium signaling and regulation of vascular tone in the cerebral parenchymal microcirculation.  Microcirculation 2012 Dec 8.  Doi:  10.1111/micc.12027.  PMID:  23216877
  7. Lavoie B, Nausch B, Zane E, Leonard M, Balemba O, Bartoo A, Wilcox R, Nelson MT, Mccarey, and Mawe G.  Disruption of Gallbladder Smooth Muscle Function is an Early Feature in the Development of Cholesterol Gallstone Disease Neurogastroenterology and Motility 2012 May 24:  10.1111/j.1365-2982.2012.01935.x.  PMID 22621672
  8. Koide M, Bonev AD, Nelson MT, and Wellman GC, Inversion of neurovascular coupling by subarachnoid blood depends on large-conductance Ca2+-activated K+ (BK) channels. Proc Natl Acad Sci USA 2012 May 22:  109(21):E1387-95.  PMID: 22547803
  9. Sonkusare SK, Bonev AD, Ledoux J, Liedtke W, Kotlikoff MI, Heppner TJ, Hill-Eubanks DC, & Nelson MT.  Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science, 2012 May 4:  336(6081):  597-601.  PMID  22556255. Editor’s Choice ( L. B. Ray, Blood Pressure Gauge. Sci. Signal. 5, ec131), featured in a Perspective in the same issue (Lederer et al., attached) and a Podcast.                                                                    . (http://podcasts.aaas.org/science_signaling/ScienceSignaling_120508.mp3). 
  10. Nausch LW, Bonev AD, Heppner TJ, Tallini YN, Kotlikoff MI, & Nelson MT.  Sympathetic nerve stimulation induces local endothelial calcium signals to oppose vasoconstriction of mouse mesenteric arteries. Am J Physiol Heart Circ Physiol, 2012 Feb 1:  302(3):  H594-602. doi: 10.1152/ajpheart.0073.2011. PMID 22140050.  Featured in a Podcast:  http://ajpheart.podbean.com/2012/03/.
  11. Dabertrand F, Nelson MT, and Brayden JE.  Acidosis dilates brain parenchymal arterioles by conversion of calcium waves to sparks to activate BK channels. Circulation Research. 2012 Jan 20; 110(2):285-294.  PMID 22095728
  12. Joshi S, Nelson MT, and Werner ME. Amplified NO/cGMP-mediated relaxation and ryanodine receptor-to-BK(Ca) channel signalling in corpus cavernosum smooth muschel from phospholamban knockout mice.  Br J Pharmacol. 2012 Jan; 165(2): 455-466  PMID 21718308
  13. Heppner TJ, Layne JJ, Pearson JM, Sarkissian H, and Nelson MT.  Unique properties of muscularis mucosae smooth muscle in guinea pigeau pig urinary bladder. Am J Physiol Regul Integr Comp Physiol. 2011 Aug 301(2):  R351-R362.  PMID 21632849
  14. Hill-Eubanks DC, Werner ME, Heppner TJ, and Nelson MT.  Calcium signaling in smooth muscle. Cold Spring Harb Perspect Biol. 2011 Sep 1; 3(9): a004549.  PMID 21709182
  15. Longden T, Dunn K, Draheim H, Nelson M, Weston A, and Edwards G.  Intermediate-conductance calcium-activated potassium channels participate in neurovascular coupling.  Br J Pharmacol. 2011 Oct;164(3):  922-933.  PMID 21506954
  16. Zvara, P., Wright, A.J., Ursiny, M., Shapiro, B., Dagrosa, L.M., Nelson, M.T., and Heppner, T.J.   A non-anesthetized mouse model for recording sensory urinary bladder activity.  Front Neurol, 2010 Nov 2; 1:127.  PMID 21188259
  17. Hannah, R.M., Dunn, K.M., Bonev, A.D., and Nelson, M.T.  Endothelial SK(ca) and IK(Ca) channels regulate brain parenchymal arteriolar diameter and cortical cerebral blood flow.  J Cereb Blood Flow Metab, 2011 May; 31(5):  1175-1186. PMID 21179072. Featured paper with commentary and journal cover.
  18. Nystoriak, M.A., O’Connor, K.P., Sonkusare, S.K., Brayden, J.E., Nelson, M.T., and Wellman, G.C.  Fundamental increase in pressure-dependent constriction of brain parenchymal arterioles from subarachnoid hemorrhage model rats due to membrane depolarization.  Am J Physiol Heart Circ Physiol, 2011 Mar; 300(3):  H803-H812.  PMID 21148767
  19. Koide M., Nystoriak M.A., Krishnamoorthy G., O’Connor K.P., Bonev, A.D., Nelson M.T., and Wellman, G.C.  Reduced Ca2+ spark activity after subarachnoid hemorrhage disables BK channel control of cerebral artery tone.  J Cereb Blood Flow Metab, 2011 Jan; 31(1):  3-16, 2011.  PMID 20736958
  20. Lu, C., Diehl, S.A., Noubade, R., Ledoux, J., Nelson, M.T., Spach, K., Zachary, J.F., Blankenhorn, E.P., and Teuscher, C.  Endothelial histamine H1 receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis.  Proc Natl Acad Sci USA, 2010 Nov. 2; 107(44):  18967-18972.  PMID 20956310
  21. Hill-Eubanks D.C., Werner M.E., and Nelson, M.T.  Local elementary purinergic-induced Ca2+ transients:  from optical mapping of nerve activity to local Ca2+ signaling networks.  J Gen Physiol, 2010 Aug; 136(2):  149-154, 2010.  PMID 20660658
  22. Lavoie B., Balemba O.B., Godfrey C., Watson C.A., Vassileva G., Corvera C.U., Nelson M.T., and Mawe G.M.  Hydrophobic bile salts inhibit gallbladder smooth muscle function via stimulation of GPBAR1 receptors and activation of KATP channels.  J Physiol, 2010 Sep 1; 588(Pt 17):  3295-3305.   PMID 28624794
  23. Nausch B., Heppner T.J., and Nelson M.T.  Nerve-Released Acetylcholine Contracts Urinary Bladder Amooth Muscle by Inducing Action Potentials Independently of IP3-Mediated Calcium Release.  Am J Physiol Regul Integr Comp Physiol, 2010 Sep; 299(3):  R878-R888.  PMID 2073989
  24. Dunn, K.M., and Nelson, M.T.   Potassium Channels and Neurovascular Coupling.  Circulation Journal, 2010 Apr; 74(4):  608-616.  PMID 20234102
  25. Girouard, H., Bonev, A.D., Hannah, R.M., Meredith, A., Aldrich, R.W., and Nelson, M.T.   Astrocytic endfoot Ca2+ and BK channels determine both arteriolar dilation and constriction.  Proceeding of the National Academy of Sciences, 2010 Feb 23; 107(8):  3811-3816.  PMID 20133576
  26. Nelson, M.T., Ledoux, J., Taylor, M., Bonev A.D., Hannah, R., Solodushko V., Shui B., Tallini, Y. and Kotlikoff, M.I. Spinning Disk Confocal Microscopy of Calcium Signalling in Blood Vessel Walls.  Microscopy and Analysis, 2010 24(2): 5-8. PMID 22506097
  27. Dunn, K.M., and Nelson, M.T.   Calcium and diabetic vascular dyscunction.  Focus on “Elevated Ca2+ sparklet activity during acute hyperglycemia and diabetes in cerebral arterial smooth muscle cells”.  American Journal of Physiology, Cell Physiology, 2010 Feb;  298(2):  C203-C205.  PMID 19907015
  28. Layne, J., Nausch, B., Olesen, S.P., and Nelson, M.T.  BK Channel Activation by NS11021 Decreases Excitability and Contractility of Urinary Bladder Smooth Muscle.  American Journal of Physiology Regulatory, Integrative and Comparative Physiology, 2010 Feb; 298(2):  R378-R384.  PMID 19923353

Honors and Awards

2013
Keynote Speaker, 6th International Conference on cGMP, Erfurt, Germany

2012

Society of General Physiologists Traveling Scholar Award, Harvard University.

2012

15th Annual James W. Fisher Distinguished Lectureship in Pharmacology, Tulane University, New Orleans, LA

2012

Keynote Speaker, FASEB Smooth Muscle Conference, Snowmass Village, CO

2011

Astor Lecturer, University of Oxford, Department of Pharmacology

2009

Swift Memorial Lecture, Columbia University, Department of Physiology and Cellular Biophysics.

2009

Lamport Lecture, University of Washington, Department of Physiology and Biophysics

2009-

University Distinguished Professor, University of Vermont

2009-

Fellow of the Biophysical Society

2009

5th David F. Bohr Lecture on Vascular Smooth Muscle, 10th International Symposium on Mechanisms of Vasodilation

2008

Graduate Student’s Choice Speaker of the Year, Department of Pharmacology & Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR.

2008

Graduate Student’s Choice Speaker of the Year, Student Research Day, University of New Mexico School of Medicine Biomedical Sci. Graduate Prog., Albuquerque, New Mexico.

2006

Distinguished Lecturer, North West Universities of England; The Universities of Liverpool and Manchester

1998-

Vermont Academy of Sciences and Engineering, member

1996

University Scholar, University of Vermont

1985-1990

Established Investigator of the American Heart Association

Funding

National Institutes of Health

P01 HL09548801, Calcium signaling in the cerebrovascular unit in health and disease, PI M.T. Nelson, Project 1 and Administrative Core.  8/1/10-7/31/15.

National Institutes of Health

R37 DK53832, Ca2+ sparks and urinary bladder smooth muscle excitability, PI: M.T. Nelson.  8/1/98-5/31/18.

Totman Medical Research Trust

PI: M.T. Nelson.  8/22/89-Indefinite. 

Fondation Leducq

Pathogenesis of Small Vessel Disease of the Brain.  North American Coordinator, M.T. Nelson; European Coordinator, A. Joutel (Paris).  10/1/12-9/30/17.

 

Last modified March 19 2014 08:45 AM