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Thomas A. Longden, PhD

Academic Title:

Assistant Professor

Primary Appointment:

Physiology

Location:

505 Howard Hall

Phone (Primary):

(410) 706-1956

Education and Training

  • B.Sc (Hons) Pharmacology, University of Manchester, United Kingdom, 2006

  • Ph.D. Pharmacology, University of Manchester, United Kingdom, 2010 

  • Postdoc Pharmacology, University of Vermont, USA, 2011-2015

 

Biosketch

Tom graduated from the University of Manchester (UK) with a B.Sc with honors in pharmacology in 2006. He subsequently joined the pharmacology graduate program at the same institution to complete his Ph.D. under the supervision of Dr. Gillian Edwards and Prof Arthur Weston. Tom's graduate studies were sponsored by a Biotechnology and Biological Sciences Research Council (BBSRC) Collaborative Award in Science and Engineering (CASE) fellowship, with Boehringer Ingelheim as an industrial sponsor, and focused on the role of the astrocytic intermediate-conductance calcium-activated potassium channel in neurovascular coupling. 

In 2011, Tom moved to the USA to begin his postdoctoral training under the direction of Prof Mark Nelson at the University of Vermont. Here, his work (sponsored by two American Heart Association Founder's Affiliate Postdoctoral Fellowships) focused on the role of vascular ion channels and G-protein coupled receptors in the control of brain blood flow. His studies demonstrated that chronic psychological stress profoundly disrupts inward-rectifier potassium channel-mediated neurovascular coupling, and revealed that the brain’s capillary network constitutes a vast ‘sensory web’, capable of translating local neural activity into vasodilatory electrical signals. These signals are then rapidly transmitted along capillaries to relax larger upstream arterioles and direct blood flow to active neurons.

Tom was promoted to Assistant Professor in 2015 and continued to work on brain capillaries, with a focus on local endothelial calcium signaling which regulates blood flow through the deep capillary bed. In 2017 he was awarded an American Heart Association Scientist Development Grant, and he joined the department of physiology at the University of Maryland School of Medicine in February 2019.

Research/Clinical Keywords

brain blood flow, neurovascular coupling, functional hyperemia, smooth muscle, endothelium, pericytes, astrocytes, ion channels, G-protein coupled receptors, ependymal cells, choroid plexus, plasticity, dementia, electrophysiology, optogenetics, multiphoton imaging

Highlighted Publications

Longden T, Dabertrand F, Koide M, Gonzales A, Tykocki N, Brayden J, Hill-Eubanks D, Nelson M (2017) “Capillary K+-sensing initiates retrograde hyperpolarization to locally increase cerebral blood flowNature Neuroscience, 20: 717-726.

  • Covered in a ‘News and Views’ article in Nature Neuroscience and featured on the May 2017 cover.
  • Recommended in F1000Prime as being of special significance in its field.

Longden T, Hill-Eubanks D, Nelson M (2016) “Ion Channel Networks in the Control of Cerebral Blood FlowJournal of Cerebral Blood Flow & Metabolism, 36(3): 492-512.

Longden T, Nelson M (2015) “Vascular Inward Rectifier K+ Channels as External K+ Sensors in the Control of Cerebral Blood FlowMicrocirculation, 22(3): 183-196.

Longden T, Dabertrand F, Hill-Eubanks D, Hammack S, Nelson M (2014) “Stress-Induced Glucocorticoid Signaling Remodels Neurovascular Coupling Through Impairment of Cerebrovascular Inwardly Rectifying K+ Channel FunctionProceedings of the National Academy of Sciences USA, 111(20): 7462-7.

Longden T, Dunn K, Draheim H, Nelson M, Weston A, Edwards G (2011) “Intermediate-Conductance Calcium-Activated Potassium Channels Participate in Neurovascular CouplingBritish Journal of Pharmacology, 164(3): 922-33.

Additional Publication Citations

Harraz O, Longden T, Hill-Eubanks D, Nelson M (2018) "PIP2 depletion promotes TRPV4 channel activity in mouse brain capillary endothelial cells" eLife. 7: e38689.

Harraz O, Longden T, Dabertrand F, Hill-Eubanks D, Nelson M (2018) "Endothelial GqPCR activity controls capillary electrical signaling and brain blood flow through PIP2 depletion" Proceedings of the National Academy of Sciences USA, 115(5): E3569-3577.

Welsh D, Longden T (2017) “Endothelial Signaling and the Dynamic Regulation of Arterial Tone: A Surreptitious RelationshipMicrocirculation, 24(3): 10.1111/micc.12370.

Tykocki N, Bonev A, Longden T, Heppner T, Nelson M (2017) “Inhibition of vascular smooth muscle inward-rectifier K+ channels restores myogenic tone in mouse urinary bladder arteriolesAmerican Journal of Physiology Renal Physiology, 312(5): F836-F847.

Klitgaard-Povlsen G, Longden T, Bonev A, Hill-Eubanks D, Nelson M (2016) “Uncoupling of Neurovascular Communication After Transient Global Cerebral Ischemia is Caused by Impaired Parenchymal Smooth Muscle KIR Channel FunctionJournal of Cerebral Blood Flow & Metabolism, 36(7): 1195-1201.

Balbi M, Ghosh M, Longden T, Vega M, Gesierich B, Hellal F, Lourbopoulos A, Nelson M, Plesnila N (2015) “Dysfunction of mouse cerebral arteries during early agingJournal of Cerebral Blood Flow & Metabolism 35(9): 1445-1453.

Villalba N, Sonkusare S, Longden T, Tran T, Sackheim A, Nelson M, Wellman G, Freeman K (2014) “Traumatic brain injury disrupts cerebrovascular tone through endothelial inducible nitric oxide synthase expression and nitric oxide gain of functionJournal of the American Heart Association, 3(6): e001474.

Research Interests

The central theme of my research is the control of blood flow in the brain, with a focus on the moment-to-moment regulation of blood flow in response to neuronal activity—a process termed ‘functional hyperemia’ and mediated by a range of mechanisms collectively termed ‘neurovascular coupling’. This complex phenomenon, which forms the basis of fMRI, involves dynamic interplay between the cells of the neurovascular unit—neurons, astrocytes, pericytes, endothelial cells and arteriolar smooth muscle. To understand the mechanisms of neurovascular coupling in health and disease, my lab utilizes a broad range of techniques, including multiphoton imaging in vivo and in brain slices, high-speed confocal imaging of calcium dynamics in the cells of the neurovascular unit, electrophysiology on freshly isolated vascular cells and on neurons and astrocytes in slices and in vivo, myography on isolated microvessels, whole-animal behavioral assays, molecular approaches, and vascular optogenetic approaches.

Our current focus is on how capillary ion channel and GqPCR activity initiates and coordinates the blood flow response to local neuronal activity and how this is disrupted in disease. Projects in the lab are centered around determining the importance of blood flow for synaptic plasticity, how the expression and function of ion channels in the vascular wall changes in response to neuronal activity, and how these phenomena are disrupted in dementia. 

We also have an interest in studying intracellular calcium dynamics in the choroid plexus epithelium, a tissue responsible for the production of cerebrospinal fluid which is essential for normal brain function, calcium dynamics in astrocytes in health and disease, and in the physiology of ependymal cells, which line the brain ventricular wall.

Awards and Affiliations

Awards

2016 Young Investigator Award

Awarded by the Cardiovascular Research Institute of Vermont.
Society of General Physiologists Annual Meeting, 2016.

2015 Symposium Award winner

Society of General Physiologists Annual Meeting, 2015.

2014 Cardiovascular Pharmacology Postdoctoral Competition

American Society for Pharmacology and Experimental Therapeutics.

Experimental Biology, 2014.

2012-2014 Durwood J Smith Award for Excellence in Pharmacology

University of Vermont Annual Pharmacology Retreat.

2016 Society of General Physiology Travel Award

Society of General Physiologists Annual Meeting, 2016.

2015 Japanese Microcirculatory Society Travel Award

10th World Congress for Microcirculation

2015 Cardiovascular Research Institute of Vermont Travel Award

Society of General Physiologists Annual Meeting, 2015.

2015 Cardiovascular Research Institute of Vermont Travel Award

Experimental Biology, 2015.

2012 ASPET Young Scientist Travel Award

Experimental Biology 2012

2005 AstraZeneca Prize in Pharmacology

 

Affiliations

2015-Present Society of General Physiologists

2011-Present American Physiological Society

2011-Present American Society for Phamacology and Experimental Therapeutics

2006-2011 British Pharmacological Society

Grants and Contracts

July 2017- June 2020 American Heart Association Scientist Development Grant

“Vascular signaling plasticity in the brain”

 

May 2017 – December 2018 NIH COBRE: Vermont Center for Behavior and Health Project Directorship

“Impact of stress on capillary-to-arteriole communication”

 

July 2014 - July 2015 American Heart Association Founders Affiliate Postdoctoral Fellowship

“Hemodynamic contributions to the control of neuronal function”  

 

July 2012 - July 2014 American Heart Association Founders Affiliate Postdoctoral Fellowship

“Neurovascular Coupling in Chronic Stress”  

 

Professional Activity

Reviewing editor   

Frontiers in Physiology

Committee memberships     

11th World Congress for Microcirculation Scientific Advisory Committee.

ISRA 2020 Scientific Advisory Committee.

Cardiovascular Research Institute of Vermont Early Career Advisory Committee.

Conference organizer            

Smooth Muscle Underground 2019, Experimental Biology 2019 Satellite, Orlando FL.

Lab Techniques and Equipment

  • Patch clamp electrophysiology
  • Multiphoton microscopy
  • Confocal microscopy
  • Pressure myography
  • Optogenetics
  • Molecular Biology

Links of Interest