Vision
A premier research center on brain blood vessels, the Totman Medical Research Trust supports an interdepartmental, highly interactive research group focused on key aspects of brain artery function from molecules to clinical applications.
Participants
Trustees
Mr. Donald Stone Jr. - Fairfax, VA
Mr. Jeffrey Stone - Waterford, NY
Mr. Donald Howard - Mount Dora, FL
Advisory Board
W. Jonathan Lederer, M.D., Ph.D. Professor and Director, Medical Biotechnology Center, University of Maryland; Visiting Professor, Department of Pharmacology, University of Vermont
Institutional Leadership
Richard L. Page, M.D.
Dean, College of Medicine
Kate Tracy, Ph.D. Senior Associate Dean for Research
Brian Cote
Associate Dean for Finance and Administration, College of Medicine
Faculty
Mark T. Nelson, Ph.D., Professor and Chair, Department of Pharmacology; Professor, Department of Molecular Physiology & Biophysics
George C. Wellman, Ph.D., Professor, Departments of Pharmacology and Surgery (Division of Neurosurgery)
Marilyn J. Cipolla, Ph.D., Professor, Departments of Neurology, Obstetrics & Gynecology, and Pharmacology
Kalev Freeman, M.D., Ph.D., Assistant Professor, Department of Surgery, Assistant Professor, Pharmacology
Osama Harraz, Ph.D., Assistant Professor, Department of Pharmacology
Grant W. Hennig, Ph.D. Research Assistant Professor, Department of Pharmacology
Thomas Heppner, Ph.D., Research Assistant Professor, Department of Pharmacology
Gerald Herrera, Ph.D., Research Assistant Professor, Department of Pharmacology
David Hill-Eubanks, Ph.D., Research Assistant Professor, Department of Pharmacology
Nicholas Klug, Ph.D., Assistant Professor, Department of Pharmacology
Masayo Koide, Ph.D., Research Assistant Professor, Department of Pharmacology
Adam Greenstein, MD, Ph.D., Guest Faculty
Publications
Mark T. Nelson, Ph.D.
- Klug NR, Sancho M, Gonzales AL, Heppner TJ, O’Brien RIC, Hill-Eubanks D, Nelson MT. Intraluminal pressure elevates intracellular calcium and contracts CNS pericytes: Role of voltage-dependent calcium channels. Proc Natl Acad Sci USA. 2023 Feb 28; 120(9): e2216421120. doi: 10.1073/pnas.2216421120. PMID: 36802432; PMCID: PMC9992766
- Mughal A, Nelson MT, Hill-Eubanks D. The post-arteriole transitional zone: a specialized capillary region that regulates blood flow within the CNS microvasculature. J Physiol. 2023 Mar; 601(5): 889-901. doi: 10.1113/JP282246. PMID: 36751860; PMCID: 9992301
- Heppner TJ, Hennig GW, Nelson MT, Herrera GM. Afferent nerve activity in a mouse model increases with faster bladder filling rates in vitro, but voiding behavior remains unaltered in vivo. Am J Physiol Regul Integr Comp Physiol. 2022 Nov 1; 323(5): R682-R693. doi: 10.1152/ajpregu.00156.2022. PMID: 36121145; PMCID: PMC9602904
- Taylor JL, Pritchard HAT, Walsh KR, Strangward P, White C, Hill-Eubanks D, Alakrawi M, Hennig G, Allan SM, Nelson MT, Greenstein AS. Functionally linked potassium channel activity in cerebral endothelial and smooth muscle cells is compromised in Alzheimer’s disease. Proc Natl Acad Sci USA. 2022 June 28; 119(26): e2204581119. doi.10.1073/pnas.2204581119. PMID: 35727988, PMCID: PMC9245656
- Sancho M, Klug NR, Senatore AJ, Hill-Eubanks DC, Nelson MT. Adenosine signaling activates ATP-sensitive K+ channels in endothelial cells and pericytes in CNS capillaries. Sci Signal. 2022 Mar 29; 15(727): eabl5405. doi: 10.1126/scisignal.abl5405. PMID: 35349300
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Osama F. Harraz, Ph.D.
- Lim XR, Harraz OF#. Mechanosensing by Endothelial Cells, Ann Rev Physiol. Accepted (# Corresponding author)
- Harraz OF. Endothelial Cell Metabolism and Vascular Function: A Paradigm Shift?, Function (Oxf). 2023 Jan 6; 4(2): zqad002. doi: 10.1093/function/zqad002. PMID: 36778750, PMCID: PMC9909363
- Harraz OF, Hegyi B, Jones DK, Krogh-Madsen T, Murfee WL, Nystoriak MA, Posnack NG, Ripplinger CM, Verrearaghavan R, Weinberg S. Diversity of cells and signals in the cardiovascular system. J Physiol. 2023 Feb 6. doi: 10.1113/JP284011. PMID: 36744541
- Bracko O, Harraz OF. Editorial: Small and mighty: Brain Capillaries in health and disease. Front Mol Neurosci. 2022 Dec 13; 15:1108978. doi: 10.3389/fnmol.2022.1108978. PMID: 36583082, PMCID: PMC9792964
George C. Wellman, Ph.D.
- Villalba, N, Wellman GC. Editorial: Inflammation and cardiovascular disease: Vascular responses, mechanisms and therapeutic implications. Front Physiol. 2022 Aug 24; 13: 995175. doi: 10.3389/fphys.2022.995175. PMID: 36091372, PMCID: PMC9449692
- Koide M, Harraz OF, Dabertrand F, Longden TA, Ferris HR, Wellman GC, Hill-Eubanks DC, Greenstein AS, Nelson MT. Differential Restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease. J Clin Invest. 2021 Sept 15; 131(18):e149029. doi: 10.1172/JCI149029. PMID: 34351870, PMCID: PMC8439604
- F, Luo MY, Yang L, Lanzino G, Chang HJ, Wellman GC. Endocrine dysfunction following stroke. J Neuroimmune Pharmacol. 2021 Jun 16: 425-436. doi: 10.1007/s11481-020-09935-6. PMID: 326621001
- Koide M, Ferris HR, Nelson MT, Wellman GC. Impaired Cerebral Autoregulation After Subarachnoid Hemorrhage: A Quantitative Assessment Using a Mouse Model. Front Physiol. 2021 Jun 8: 12:688468. doi: 10.3389/fphys.2021.688468. PMID: 34168571, PMCID: PMC8218876
Marilyn J. Cipolla, Ph.D.
- Alkyed N and Cipolla MJ. Role of Endothelial Cells and Platelets in COVID-Related Cerebrovascular Events. Stroke. 2022 Jul; 53(8): 2389-2392. doi: 10.1161STROKEAHA122039971, PMID: 35674044, PMCID: PMC9232245
- Kahn SS, Gooding H, Brewer LC, Canobbio MM, Cipolla MJ, Grobman WA, Lewey J, Michos ED, Miller EC, Perak AM, Wei GS. Optimizing Pre-Pregnancy Cardiovascular Health to Improve Outcomes in Pregnant and Postpartum Individuals and Offspring: A Scientific Statement from the American Heart Association. Circulation. 2023 Feb 14; 147(7): e76-e91. doi: 10.1161/CIR.0000000000001124. PMID: 36780391, PMCID: PMC10080475
- Cipolla MJ, Tremble ST, DeLance N, Johnson AC. Worsened stroke outcome in a model of preeclampsia is associated with poor collateral flow and oxidative stress. Stroke. 2023 Feb; 54(2): 354-363. doi: 10.1161/STROKEAHA.122.041637. PMID: 36689585, PMCID: PMC9888018
- Cipolla MJ, Alkayed NJ. Vascular Biology of Dementia. Stroke. 2023 Mar; 54(3): 646-647. doi: 10.1161/STROKEAHA.123.042298. PMID: 36848429
- Linfante I, et al. HEMERA 1 (CarboxyHEMoglobin OxygEn delivery for Revascularization in Acute Stroke): randomized controlled phase 1 clinical trial. Stroke. (Submitted)
Kalev Freeman, M.D.
- Villalba N, Sackheim AM, Lawson MA, Haines L, Nelson MT, Freeman K. The polyanionic drug suramin neutralizes histones and prevents endotheliopathy. J of Immunology. 2023. Accepted – Preprint. doi: 10.1101/2021/12/09/469611
- Woodman R, Miller C, Student J, Freeman K, Perl D, Lockette W. Alpha-methyltyrosine (aMT) reduces the acute cardiovascular and behavioral sequelae in a murine model of traumatic brain injury (TBI). J Trauma Acute Care Surg. 2023 May 11. doi: 10.1097/TA.0000000000004023. PMID: 37165479
- Wang C, Dong C, Lu Y, Freeman K, Wang C, Guo M. Digestion behavior, in vitro and in vivo bioavailability of cannabidiol in emulsions stabilized by whey-protein-maltodextrin conjugate: Impact of carrier oil. Colloids Surf B Biointerfaces. 2023 Jan 18; 223:113154. PMID: 36708645
- Coleman JR, Moore EE, Schmitt L, Hansen K, Dow N, Freeman K, Cohen MJ, Silliman CC, Estradiol provokes hypercoagulability and affects fibrin biology: A mechanistic exploration of sex dimorphisms in coagulation. J Trauma Acute Care Surg. 2023 Feb 1; 94(2): 179-186. doi: 10.1097/TA.0000000000003822. PMID: 36694329, PMCID: PMC9881840
- Huerta de l Cruz S, Santiago-Castaneda CL, Rodriguez-Palma EJ, Medina-Terol GJ, Lopez-Preza FL, Rocha L, Sanchez-Lopez A, Freeman K, Centurion D. Targeting hydrogen sulfide and nitric oxide to repair cardiovascular injury after trauma. Nitric Oxide. 2022 Dec 1; 129:82-101. doi: 10.1016/j.niox.2022.10.003. PMID: 36280191 Review
- Lawson MA, Holle LA, Dow NE, Hennig G, de Laat B, Moore HB, Moore EE, Cohen MJ, Bouchard BA, Freeman K, Wolberg AS. Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy. J Trauma Acute Care Surg. 2022 Nov 1; 93(5): 579-587. doi: 10.1097/TA.0000000000003723. PMID: 35687811, PMCID: PMC9613511
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Adam S. Greenstein, M.D., Ph.D.
- Worton SA, Pritchard HAT, Greenwood SL, Alakrawi M, Heazell AEP, Wareing M, Greenstein A, Myers JE. Kynurenine Relaxes Arteries of Normotensive Women and Those with Preeclampsia. Cir Res. 2021 May 28; 128(11): 1679-1693. doi: 10.1161/CIRCRESAHA.120.317612. PMID: 33656370, PMCID: PMC8154175
- Greenstein AS, Kadir SZAS, Csato V, Sugden SA, Baylie RA, Eisner DA, Nelson MT. Disruption of Pressure-Induced Ca2+ Spark Vasoregulation of Resistance Arteries, Rather Than Endothelia Dysfunction, Underlies Obesity-Related Hypertension. Hypertension. 2020 Feb; 75(2): 539-548. doi: 10.1161/HYPERTENSIONAHA.119.13540. PMID: 31865779, PMCID: PMC7055934
- Pritchard HAT, Griffin CS, Yamasaki E, Thakore P, Lane C., Greenstein AS, Earley S. Nanoscale coupling of junctophilin-2 and ryanodine receptors regulates vascular smooth muscle cell contractility. Proc Natl Acad Sci USA. 2019 Oct 22; 116(43): 21874-21881. doi: 10.1073/pnas.1911304116. PMID: 31591206, PMCID: PMC6815135