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") in the CNS.  To study this we have a CADASIL mouse model that carries one of the human mutations of NOTCH 3 (R169C) known to cause the human disease, and displays many of the clinical features of the disease including the white matter lesions associated with dementia.  Mutant Notch 3 leads to accumulation of extracellular proteins in the parenchymal arterioles of the CNS and causes an early cerebrovascular dysfunction (loss of tone) through upregulation voltage-dependent potassium channels.
  2. To understand how sympathetic nerves, smooth muscle cells and endothelial cells communicate ("vascular crosstalk") to control the function of resistance-sized peripheral arteries.  We have made a number of important contributions to this field including; the fist evidence that expression of endothelial cell SK3 channels modulates blood pressure (Taylor et al., Circ Res, 2003), the first measurements of local IP3-mediated Ca2+ signals ("pulsars") at the myoendothelial projections (Ledoux et al., PNAS, 2008), and of elementary Ca2+ signals ("sparklets") through single TRPV4 channels (Sonkusare et al., Science, 2012). 
  3. To understand the roles of ion channels and calcium signaling in the control of urinary bladder function in health and disease.

Research approaches cover the spectrum from molecular, cellular, intact tissue, whole organ and in vivo (local CBF, blood pressure, urodynamics). 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. 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 objectives 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

Drs. Bonev, Dabertand, Heppner, Hill-Eubanks, Longden & Tykocki

Postdoctoral Associates and Fellows

D. Collier, A. Gonzales, O. Harraz, J. Scheilfenbaum

Laboratory Research Technicians

Max Ross and Gaelin Kopec-Belliveau

Recent Publications

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

  1. Mah W, Sonkusare SK, Wang T, Azeddine B, Pupavac M, Carrot-Zhang J, Hong K, Mejewski J, Harvey EJ, Russell L, Chalk C, Rosenblatt DS, Nelson MT, Sequin C.  Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head.  J Med Genet.  2016 June 21, doi:  10.1136/jmedgenet-2016-103829.  PMID:  27330106.                                                       
  2. Povlsen GK, Longden TA, Bonev AD, Hill-Eubanks DC, Nelson MT.  Uncoupling neurovascular communication after transient global cerebral ischemia is caused by impaired parenchymal smooth muscle Kir channel function.  J Cereb Blood Flow Metab.  2016 Apr 6, doi:  10.1177/0271678X16638350.  PMID:  27052838, PMCID:  4929704 .                                                                                                                        
  3. Gonzalez EJ, Heppner TJ, Nelson MT, VIzzard MA.  Purinergic signalling underlies transforming growth factor-beta mediated bladder afferent nerve hyperexcitability.  J Physiol.  2016 Mar 23, doi:  10.1113/JP272148.  PMID:  27006168, PMCID:  PMC4929319.                                                                                                                                                                                       
  4. Heppner TJ, Tykocki NR, Hill-Eubanks D, Nelson MT.  Transient contractions of urinary bladder smooth muscle are drivers of afferent nerve activity during filling.  J Gen Physiol.  2016 Mar 14, doi:  10.1085/jgp.201511550.  PMID:  26976828, PMCID:   PMC4810069.                                                                                                                                                                                       
  5. Sonkusare SK, Dalsgaad T, Bonev AD, Nelson MT.  Inward rectifier potassium (Kir2.1) channels as end-stage boosters of endothelium-dependent vasodilators.  J Physiol.  2016 Feb 3, doi:  10.1113/jp271652.  PMID:  26840527, PMCID:  PMC4908010.                                                                                                                                                                                      
  6. Villalba N, Sackheim A, Nunez I, Hill-Eubanks D, Nelson MT, Wellman GC, Freeman K.  Traumatic brain injury causes endolthelium dysfunction in systemic microcirculation through arginase-1-dependent uncoupling of endothelial nitric oxide synthase.  J Neurotrauma.  2016 Jan 13.  doi:  10.1089/neu.2015.4340.  PMID:  26757855.                                                                                              
  7. Longden TA, Hill-Eubanks DC, Nelson MT.  Ion channel networks in the control of cerebral blood flow.  J Screb Blood Flow Metab.  2015 Nov 9.  doi:  10.1177/0271678X15616138.  PMID:  26661232, PMCID:  PMC57943103                                                                   
  8. Capone C, Cognat E, Ghezali L, Baron-Menguy C, Aubin D, Mesnard L, Stohr H, Domenga-Denier V, Nelson MT, Joutel A, Reducing Timp3 or vitronectin ameliorates disease manifestations in CADASIL mice. Ann of Neurool. 2015 Dec 9, doi: 10.1002/1n1.24573.  PMID:  26648042

  9. Ye W, Chang RB, Bushman JD, Tu YH, Mulhall EM, Wilson CE, Cooper AJ, Chick WS, Hill-Eubanks DC, Nelson MT, Kinnamon SC, Liman ER. K+ channel Kir2.1 K+ channel functions in tandem with proto influx to mediate sour taste transduction. Pro Natl Acad Sci USA. 2015 (Epublished Dec. 1, 2015) doi: 10.1073/pnas.1514282112. PMID: 26627720, PMCID:  PMC4720319

  10. Tykocki NR, Nelson MT. Location, Location, Location. Juxtaposed calcium-signaling microdomains as a novel model of the vascular smooth muscle myogenic response. J Gen Physiol. 2015 Aug: 146(2): 129-132. doi: 10.1085/jgp.201511468. PMID: 26216858. PMCID: PMC4516781

  11. Mingin GC, Heppner TJ, Tykocki NR, Erickson CS, Vizzard MA, Nelson MT. Social stress in mice induces urinary bladder overactivity and increases TRPV1 channel-dependent afferent nerve activity. Am J Physiol Regul Integr Comp Physiol. 2015 July 29. doi: 10.1152/ajpregu.00013.2015. PMID: 26224686

  12. Mann KG, Freeman K, Esmond CT, Wisnewski S, Tracy RP, Kindzelski AL, Pusateri A, Banerjee A, Brass LF, Brummel-Ziedins KE, Butenas S, Cohen MJ, Diamond SL, Moore EE, Morrissey JL, Nelson MT, Park MS, Ruf W, Shupp JW, Spearry JL, Spiess BD, Stalker TJ, Zuckerbraun BS. TACTIC: Trans-Agency Consortium for Trauma-Induced Coagulopathy. J Thromb Haemost. 2015 Jun; 13 Suppl 1: S63-S71. doi: 10.1111/jth.12981. PMID: 26149052, PMCID: PMC4498273

  13. Balbi M, Ghosh M, Longden TA, Jativa Vega M, Gesierich B, Hellal F, Lourbopoulos A, Nelson MT, Plesnila N. Dysfunction of mouse cerebral arteries during early aging. J Cereb Blood Flow Metab. 2015 Jun 10. doi: 10.1038/jcbfm.2015.107. PMID: 26048694

  14. Collier DM, Hill-Eubanks DC, Nelson MT. Orchestrating Ca2+ influx through CaV1.2 and CaV3.x channels in human cerebral arteries. J Gen Physiol. 2015 Jun; 145(6): 481-483. doi: 10.1085/jgp.2015.11411. PMID: 2609543, PMCID: PMC 4442783

  15. Joutel A, Haddad I, Ratelade J, Nelson MT. Perturbations of the cerebrovascular matrisome: a convergent mechanism in small vessel disease of the brain? J Cereb Blood Flow Metab. 2015 Apr 8. doi: 10.1038/jcbfm.2015.62. PMID: 25853907

  16. Dabertrand F, Kroigaard C, Bonev AD, Cognat E, Dalsgaard T, Domenga-Denier V, Hill-Eubanks DC, Brayden JE, Joutel A, Nelson MT. Potassium channelopathy-like defect underlies early-stage cerebrovascular dysfunction in a genetic model of small vessel disease. Proc Natl Acad Sci USA. 2015 Feb 17: 112(7): E796-E805. doi: 10.1073/pnas.1420765112. PMID: 25646445, PMCID: PMC4343103

  17. Longden TA, Nelson MT. Vascular Inward Rectifier K+ Channels as External K+ Sensors in the Control of Cerebral Blood Flow. Microcirculation. 2015 Jan 31; doi: 10.1111/micc.12190. PMID: 25641345, PMCID: PMC4404517

  18. Villalba N, Sonkusare SK, Longden TA, Tran TL, Sackheim AM, Nelson MT, Wellman GC, Freeman K. Traumatic brain injury disrupts cerebrovascular tone through endothelial inducible nitric oxide synthase expression and nitric oxide gain of function. J Am Heart Assoc, 2014 Dec 19; 3(6), pii: e001474. doi: 10.1161/JAHA.114.001474. PMID: 25527626, PMCID: PMC4338739

  19. Longden TA, Hammack SE, Nelson MT. Channeling Stress: inwardly-rectifying K+ channels in stress and disease, Channels (Austin). 2014: 8(4): 296-297. PMID: 25478622

  20. Hill-Eubanks DC, Gonzales AL, Sonkusare SK, Nelson MT. Vascular TRP Channels: Performing Under Pressure and Going with the Flow. Physiology Review. 2014 Sept; 29(5): 343-360. doi: 10.1152/physiol.00009.2014. PMID: 25180264, PMCID: PMC4214829

  21. 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, PMCID: PMC4187184

  22. 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, PMCID: 4403000, with Perspective: Pooneh B, Garland CJ. Scaffolding Builds to Reduce Blood Pressure, Science Signaling. 2014 July 8; 7(333) pe16. doi: 10.1126/scisignal.2005527

  23. 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, PMCID: PMC4152884

  24. 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, PMCID: PMC4170587

  25. 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

  26. 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
     
  27. 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: PMC396263

  28. 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

Honors and Awards

  • 2016 Keynote Speaker, FASEB Smooth Muscle Conference, Lisbon, Portugal
  • 2016 Vermont Academy of Arts and Sciences, Fellowship
  • 2015 Thomas C. Vary Distinguished Lecture, University of Pennsylvania, Hershey, PA
  • 2015 Keynote Speaker, Society of General Physiologists Symposium on Macromolecular Local Signaling Complexes, Marine Biological Laboratory, Woods Hole
  • 2015 American Physiological Society, Annual Reviews Award for Scientific Reviewing
  • 2015 Kaley Lecture, Experimental Biology 2015, Boston MA, sponsored by APS Cardiovascular Section and the Microcirculation Society
  • 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
 7/1/14- 6/30/19
1R01HL121706-01A1, Regulation of myoendothelial function by signaling microdomains in hypertension, PI M.T. Nelson 
National Institutes of Health
8/1/1998-5/31/2018
R37 DK53832, Ca2+ sparks and urinary bladder smooth muscle excitability, PI: M.T. Nelson.
National Institutes of Health
 9/30/13-6/30/2018
UM1HL120877, Analysis and Characterization of Trauma-Induced Coagulopathy, PI K.G. Mann, M.T. Nelson Lead Project 12 and Co-I Project 1
Totman Medical Research Trust
8/22/1989-Present
Cerebrovascular Research, 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).
European Union 1/1/2016 - 12/31/2020666881 Horizon 2020, Small vessel disease in a mechanistic perspective: Targets for intervention, PI for WP1, Co-PI for WP2-5 (Partnering with 11 Europenan Institutions)