Update Your ProfileAcademic Title:
Assistant Professor
Primary Appointment:
Pharmacology & 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. In 2020 he received the NIH Directors New Innovator Award and in 2023 was elected as a Fellow of the American Physiological Society Cardiovascular Section.
Research/Clinical Keywords
brain blood flow, neurovascular coupling, functional hyperemia, smooth muscle, endothelium, pericytes, astrocytes, neurons, ion channels, G-protein coupled receptors, ependymal cells, choroid plexus, plasticity, dementia, Alzheimer's disease, electrophysiology, optogenetics, multiphoton imaging
Highlighted Publications
Longden T*, Hariharan A, Zhao G, Lederer WJ. (2022) “Pericytes and the Control of Blood Flow in Brain and Heart”. Annual Review of Physiology 85: 137-164.
*Co-first and co-corresponding author.
Hariharan A, Robertson C, Garcia D, Longden T (2022) “Brain capillary pericytes are metabolic sentinels that control blood flow through a KATP channel-dependent energy switch”. Cell Reports, 41: 111872.
- In the top 10% of most-viewed preprints within the first week of its publication on bioRxiv.
- Featured on the cover of the Cell Reports December 27th 2022 issue.
Longden T*, Mughal A, Hennig G, Harraz O, Shui B, Lee F, Lee J, Reining S, Kotlikoff M, Konig G, Kostenis E, Hill-Eubanks D, Nelson M (2021) “Local IP3 receptor-mediated Ca2+ signals compound to direct blood flow in brain capillaries”. Science Advances. 7: eabh0101.
*Co-first and co-corresponding author.
Hariharan A, Weir N, Robertson C, He L, Betsholtz C, Longden T (2020) “The ion channel and GPCR signaling toolkit of CNS pericytes” Frontiers in Cellular Neuroscience 14: 423.
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 flow” Nature 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 Flow” Journal 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 Flow” Microcirculation, 22(3): 183-196.
- Selected as a Featured Article by The Microcirculatory Society.
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 Function” Proceedings of the National Academy of Sciences USA, 111(20): 7462-7.
- Selected as Editor’s Choice in Science Signaling.
- Selected for Commentary in Channels.
Longden T, Dunn K, Draheim H, Nelson M, Weston A, Edwards G (2011) “Intermediate-Conductance Calcium-Activated Potassium Channels Participate in Neurovascular Coupling” British Journal of Pharmacology, 164(3): 922-33.
Additional Publication Citations
Koide M, Harraz O, Dabertrand F, Longden T, Ferris H, Wellman G, Hill-Eubanks D, Greenstein A, Nelson M (2021) “Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel diseases” Journal of Clinical Investigation, 131: e149029.
Rosehart A, Longden T, Weir N, Fontaine J, Joutel A, Dabertrand F (2021) “Prostaglandin E2 dilates intracerebral arterioles when applied onto capillaries, implication in small vessel diseases” Frontiers in Aging Neuroscience 13: 402.
Dabertrand F, Harraz O, Koide M, Longden T, Rosehart A, Hill-Eubanks A, Joutel A, Nelson M (2021) “PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity” Proceedings of the National Academy of Sciences USA 118: e2025998118.
Mughal A, Sackheim A, Sancho M, Longden T, Russell S, Lockette W, Nelson M, Freeman K. (2020) “Impaired capillary-to-arteriolar electrical signaling after traumatic brain injury.” Journal of Cerebral Blood Flow & Metabolism 41(6): 1313-1327.
Cleary C, Moreira T, Takakura A, Nelson M, Longden T, Mulkey D. (2020) “Vascular control of the CO2/H+-dependent drive to breathe in mice.” eLife. 9: e59499.
Moshkforoush A, Ashenagar B, Harraz O, Dabertrand F, Longden T, Nelson M, Tsoukias N. (2020) "Capillary Kir channel as sensor and amplifier of neuronal signals: modeling insights on K+-mediated neurovascular communication." Proceedings of the National Academy of Sciences USA. 117(28): 16626-16637.
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 Relationship” Microcirculation, 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 arterioles” American 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 Function” Journal 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 aging” Journal 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 function” Journal 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 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 plasticity in blood delivery to meet neuronal metabolic needs, how the expression and function of ion channels in the vascular wall changes in response to neuronal activity, how endothelial cells and pericytes coordinate brain blood flow, and how these phenomena are disrupted in dementia. Our primary pathological focus is Alzheimer's disease, in which brain blood flow disturbances are an early feature and are thought to be a key driver of disease progression. To support our work we are currently funded by awards from NINDS and NIA.
Awards and Affiliations
Awards
2023 Fellow of the American Physiological Society Cardiovascular Section
2020 NIH Directors New Innovator Award
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
September 2020-August 2025 National Institute on Aging (R01)
"Pericytes as metabolic sentinels in the control of brain blood flow in health and Alzheimer's disease"
August 2020-July2025 NIH New Innovator Award (DP2, NINDS)
"Vascular Signaling Plasticity - Novel Concepts and Tools for Studying Neurovascular Interactions in Health and Disease"
July 2019-June 2021 American Heart Association Innovative Project Award
“Blood flow in Learning and Memory”
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”
In the News
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
- Viral transfection
- Molecular Biology