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 my laboratory is to understand the control of smooth muscle and endothelial cell function by ion channels and calcium signaling, with an emphasis on the cerebral circulation. My early studies of mathematics and neural sciences reflected my desire to apply quantitative tools to understand important physiological issues.  After my doctoral studies with Professor Mordecai Blaustein (Neural Sciences, Washington University) on ion transport in giant single cells from barnacle muscle (the muscle equivalent of the squid giant axon), I trained with Professor Peter Läuger and made some of first measurements of single ion channels in planar lipid bilayers.

 

My laboratory’s research interests include elucidating the mechanisms by which cerebral blood flow is controlled to meet the diverse and ever-changing demands of active neurons and how these mechanisms are disrupted in small vessel disease (SVD)—a major cause of stroke and dementia.  Dr. Nelson and colleagues have unraveled many of the major mechanisms that control cerebrovascular function, including the discovery of local calcium signals (“sparks”), which counter-intuitively oppose vasoconstriction.  They have recently shown that brain capillaries act as a neural activity-sensing network by initiating and transmitting an electrical signal, mediated by potassium channel activation, that propagates through the interconnected endothelial cells comprising the capillaries that line all blood vessels.  This concept explains the rapid and coordinated delivery of blood to active neurons.  Using a mouse model of a monogenic form of SVD, they have discovered early defects that result in a loss of this electrical signaling mechanism and impaired delivery of blood to active neurons—defects that involve changes in extracellular matrix composition.  The near-term goals of Nelson laboratory researchers are to create an integrated view of electrical, calcium and related regulatory signaling mechanisms at molecular, biophysical, and computational-modeling levels by examining their operation in increasingly complex segments of the brain vasculature ex vivo, in vivo, and in silico.  Ultimately, they propose to weave these research threads together to create a systems-level view of physiological signaling in the brain microcirculation, and test the concept that gradual degradation of this sensory web and the attendant progressive decay of cerebrovascular function contributes to SVDs of the brain.

 

People in the Lab

Recent Publications

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

  1. Kabmann M, Szijarto IA, Garcia-Prieto CV, Fan G, Schleifenbaum J, Anistan YM, Tabeling C, Shi Y, le Noble F, Witzenrath M, Huang Y, Marko L, Nelson MT, Gollasch M.  Role of Ryanodine Type 2 Receptors in Elementary Ca2+ Signaling in Arteries and Vascular Adaptive Responses.  J Am Heart Assoc.  2019 May 7; 8(9): e010090.  doi:  10.1161/JAHA.118.010090.  PMID:  31030596, PMCID:  PMC6512102
  2. Collier DM, Villalba N, Sackheim AM, Bonev AD, Miller ZD, Moore JS, Shui B, Lee JC, Lee FK, Reining S, Kotlikoff MI, Nelson MT, Freeman K.  Extracellular histones induce calcium signals in the endothelium of resistance-sized mesenteric arteries and cause loss of endothelium-dependent dilation.  Am J Physiol Heart Circ Physiol.  2019 Mar 8.  doi:  10.1152/ajpheart.00655.2018.  PMID:  30848676
  3. Tykocki NR, Heppner TJ, Dalsgaard T, Bonev AD, Nelson MT.  The Kv7 channel activator retigabine suppresses mouse urinary bladder afferent nerve activity without affecting detrusor smooth muscle K+ channel currents. J Physiol. 2018 Dec 7.  doi:  10.1113/JP277021.  PMID:  30536555, PMCID:  PMC6355639
  4. Gomes C, Gayden T, Bajic A, Harraz OF, Pratt J, Nikbakht H, Bareke E, Diniz M, Castro WH, St-Onge P, Sinnett D, Han H, Rivera B, Mikael L, De Jay N, Kleinman C, Valera E, Bassenden A, Berghuis A, Majewski J, Nelson MT, Gomez R, Jabado N. TRPV4 and KRAS and FGFR1 gain-of-function mutations drive giant cell lesions of the jaw.  Nature Comm. 2018 Nov 1;  9(1):  4572.  doi:  10.1038/s41467-018-06690-4.  PMID:  30385747, PMCID:  PMC6212533
  5. Sheehe JL, Bonev AD, Schmoker AM, Ballif BA, Nelson MT, Moon TM, Dostmann WR.  Oxidation of cysteine 117 stimulates constitutive action of the type 1α cGMP-dependent protein kinase.  J Biol Chem.  2018 Sep 11.  doi:  10.1074/jbc.RA118.004363. PMID:  30206122, PMCID:  PMC6204908
  6. Chan SL, Nelson MT, Cipolla MJ.  Transient Receptor Potential Vanilloid-4 Channels Are Involved in Diminished Myogenic Tone in Brain Parenchymal Arterioles in Response to Chronic Hyperfusion in Mice.  Acta Physiol (Oxf).  2018 Aug 28:  e13181.  doi:  10.1111/apha.13181.  PMID:  30153398, PMCID:  PMC6380684
  7. Tykocki NR, Heppner TJ, Erikson CS, van Batavia JP, Vizzard MA, Nelson MT, Mingin GC.  Development of stress-induced bladder insufficiency requires functional TRPV1 channels.  Am J Physiol Renal Physiol.  2018 Aug 8.  doi:  10.1152/ajprenal.00231.2018.  PMID:  30089031, PMCID: PMC6336983
  8. Harraz OF, Longden TA, Hill-Eubanks D, Nelson MT.  PIP2 depletion promotes TRPV4 channel activity in mouse brain capillary endothelial cells.  eLife.  2018 Aug 7; 7.  doi:  10.7554/eLife.38689.  PMID:  30084828, PMCID:  PMC6117155
  9. Heppner TJ, Hennig GW, Nelson MT, May V, Vizzard MA.  PACAP38-Mediated Bladder Afferent Nerve Activity Hyperexcitability and Ca2+ Activity in Urothelial Cells from Mice.  J Mol Neurosci.  2018 July 19. doi:  10.1007/s12031-018-1119-x.  PMID:  30022438, PMCID:  PMC6339595
  10. Harraz OF, Longden TA, Dabertrand F, Hill-Eubanks DC, Nelson MT.  Endothelial GqPCR activity controls capillary electrical signaling and brain blood flow through PIP2 depletion.   Proc Natl Acad Sci USA.  2018 Apr 10, 10;  115(15):  E3569-E3577.  doi:  10.1073/pnas.1800201115.  PMID:  29581272, PMCID:  PMC5899484

Honors and Awards

  • 2019 Member, National Academy of Sciences
  • 2019 Kenneth E. Avis Professorship Award, University of Tennessee Health Science Center, Memphis, TN
  • 2019-2026  Outstanding Investigator Award (R35) from the NIH (NHLBI)
  • 2018 Inaugural James L. Kenyon Visiting Professor, University of Nevada, Reno, NV
  • 2018 Keynote Speaker, Society of Urodynamics and Female Urology Annual Meeting SUFU 2018, Austin, TX
  • 2017 Keynote Speaker, International Symposium on Resistance Arteries 2017, Manchester, UK
  • 2017 The First Kathryn M. Gauthier, Endowed Lecture, Medical College of Wisconsin, Milwaukee, WI
  • 2016 Fellow, Vermont Academy of Arts and Sciences
  • 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

NIH  1R35 HL140027-01 (Outstanding Investigator Award)  Capillaries as a sensory web that controls cerebral blood flow in health and disease.  This comprehensive research Program extends the research in 1R01 HL121706 and 1R01 HL131181 on the regulation of cerebral blood flow.  PI:  M.T. Nelson  01/01/19 - 12/30/26

NIH  1R01NS110656  Ion channel dysfunction in small vessel disease of the brain.  PI:  M.T. Nelson  04/15/19 - 03/31/24

European Union  666881 Horizon 2020, Small vessel disease in a mechanistic perspective: Targets for intervention, PI for WP1, Co-PI for WP2-5 (Partnering with 11 European Institutions)   01/01/2016 - 12/31/2020

Totman Medical Research Trust   Cerebral Vascular Research, PI:  M. T. Nelson  8/22/1989-Present

Fondation Leducq  Pathogenesis of Small Vessel Disease of the Brain. North American Coordinator, M.T. Nelson; European Coordinator, A. Joutel (Paris)  10/1/2012-9/30/2019

NIH  5UM1 HL120877  Central role of phospholipid scramblases in TIC.  This proposal examines whether Ca2+ dependent TMEMB16F scramblase activity in platelets, RBCs and the endothelium is the focal point in the pathogenesis of TIC.   PI Morrissey - Project PI  M.T. Nelson  06/01/19 - 05/31/21