University of Vermont

College of Medicine

Department of Pharmacology

nelsonlab

Nelson Lab

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

Postdocs Albert Gonzales, Thomas Longden and Nathan Tykocki

 

Laboratory Research Technicians

Technicians Samantha O'Dwyer and Jessica Pearson

Recent Publications

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

  1. Mingin GC, Peterson A, Erickson CS, Nelson MT, Vizzard MA. Social stress induces changes in urinary bladder function, bladder NGF content and generalized bladder inflammation in mice. Am J Physiol Regul Integr Comp Physiol. 2014 Aug 6. pii: ajpregu.00500.2013. E pub ahead of print. PMID: 25100077
  2. Sonkusare SK, Dalsgaard T, Bonev AD, Hill-Eubanks DC, Kotlikoff MI, Scott JD, Santana LF, Nelson MT. AKAP150-dependent cooperative TRPV4 channel gating is central to endothelium-dependent vasodilation and is dirupted in hypertension. Science Signaling. 2014 Jul 8. doi: 10.1126/scisignal.2005052. Journal cover. PMID: 25005230
  3. Nausch B, Rode F, Jorgensen S, Nardi A, Korsgaard MP, Hougaard C, Brown WD, Bonev AD, Dyhring T, Strobeak D, Olesen SP, Christophersen P, Grunnet M, Nelson MT, ROnn LC. NS19504: a novel BK channel activator with relaxing effect on bladder smooth muscle spontaneous phasi contractions. J Pharmacol Exp Ther. 2014 Jun 20. doi: 10.1124/jpet.113.212662. PMID: 24951278
  4. Gonzales AL, Yang Y, Sullivan MN, Sanders MN, Sanders L, Dabertrand F, Hill-Eubanks DC, Nelson MT, Earley S. A PLCy1-Dependent, Force-Sensitive Signaling Network in the Myogenic Constriction of Cerebral Arteries. Science Signaling. 2014 May 27. doi: 10.1126/scisignal.2004732. PMID: 24866019
  5. Longden TA, Dabertrand F, Hill-Eubanks DC, Hammack SE, Nelson MT. Stress-induced glucocorticoid signaling remodels neurovascular coupling through impairment of cerebrovascular inwardly rectivying K+ channel function; Proc Natl Acad Sci USA. 2014 May 7. doi: 10.1073/pnas.1401811111. PMID: 24808139, PMCID: PMC4034203
  6. Mercardo J, Baylie R, Navedo MF, Yuan C, Scott JD, Nelson MT, Brayden JE, Santana LF. Local control of TRPV4 channels by AKAP150-targeted PKC in arterial smooth muscle. J Gen Physiol. 2014 May; 143(5): 559-575. doi: 10.1085/jgp.201311050. PMID: 24778429, PMCID: PMC4003184
  7. 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.  doi: 10.1152/ajpheart.00866.2013. PMID:  24508642, PMCID: PMC3962638
  8. Dunn KM, Nelson MT.  Neurovascular signaling in the brain and the pathological consequences of hypertension. Am J Physiol Heart Circ Physiol.  2014 Jan1. doi: 10.1152/ajpheart.00364.2013.  PMID:  24163077, PMCID: PMC3920149
  9. 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, PMCID: PMC3790940
  10. 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, PMCID: PMC3625327 
  11. 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.  doi: 10.1038/jcbfm.2013.9.  PMID:  23385200, PMCID: PMC3618402
  12. 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, PMCID: PMC3612564
  13. 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.  doi: 10.1111/j.1365-2982.2012.01935.x.  PMID 22621672, PMCID: PMC3378777
  14. Koide M, Bonev AD, Nelson MT, 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.  doi: 109(21):E1387-95.  PMID: 22547803, PMCID: PMC3361424
  15. 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.  doi: 10.1126/science.1216283. PMID  22556255, PMCID: PMC3715993. 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
  16. 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, PMCID: 3353782.  Featured in a Podcast.
  17. Dabertrand F, Nelson MT, 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.  doi: 10.1161/CIRCRESAHA.111.258145. PMID 22095728, PMCID: PMC3505882
  18. Joshi S, Nelson MT, 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. doi: 10.1111/j.1476-5381.2011.01569.x.  PMID: 21718308, PMCID: PMC3268198
  19. Heppner TJ, Layne JJ, Pearson JM, Sarkissian H, 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.  doi: 10.1152/ajreg.00656.2010. PMID 21632849, PMCID: PMC3154705
  20. Hill-Eubanks DC, Werner ME, Heppner TJ, Nelson MT.  Calcium signaling in smooth muscle. Cold Spring Harb Perspect Biol. 2011 Sep 1; 3(9): a004549.  doi: 10.1101/cshperspect.a004549. PMID 21709182, PMCID: PMC3181028
  21. Longden T, Dunn K, Draheim H, Nelson MT, Weston A, and Edwards G.  Intermediate-conductance calcium-activated potassium channels participate in neurovascular coupling.  Br J Pharmacol. 2011 Oct; 64(3): 922-933.  doi: 10.1111/j.146-4381.2011.01447.x. PMID 21506954, PMCID: PMC3195915
  22. Hannah RM, Dunn KM, Bonev AD, Nelson MT  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. doi: 10.1038/jcbfm.2010.214. PMID 21179072, PMCID: PMC3099631. Featured paper with commentary and journal cover.

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, 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 Sciences Graduate Program, Albuquerque, NM
2006 Distinguished Lecturer, North West Universities of England; The Universities of Liverpool and Manchester
1998- Member, Vermont Academy of Sciences and Engineering
1996 University Scholar, University of Vermont
1985-1990 Established Investigator, American Heart Association

Funding

National Institutes of Health
8/1/2010 - 7/31/2015
P01 HL09548801, Calcium signaling in the cerebrovascular unit in health and disease, PI M.T. Nelson, Project 1 and Administrative Core. 
National Institutes of Health
8/1/1998-5/31/2018
R37 DK53832, Ca2+ sparks and urinary bladder smooth muscle excitability, PI: M.T. Nelson.
Totman Medical Research Trust
8/22/1989-Present
PI: M.T. Nelson.
Fondation Leducq
10/1/2012-9/30/2017
Pathogenesis of Small Vessel Disease of the Brain. North American Coordinator, M.T. Nelson; European Coordinator, A. Joutel (Paris).

Last modified November 24 2014 11:02 AM