Totman Medical Research Trust

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

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Research Technical Support

Hannah Fallon
Research Technician, Herrera Laboratory

Michael Ippolito
Research Technician, Harraz Laboratory

Nathan Stine
Research Technician, Wellman Laboratory 

Adrian Sackheim
Research Technician, Freeman Laboratory

Sarah Tremble
Senior Research Technician, Cipolla Laboratory

Natalie Cashen
Senior Research Technician, Nelson Laboratory

Post-Doctoral Trainees

Mohammad El-Mahdy, Ph.D.

Postdoctoral Associate, Harraz Lab

Emily Xin Rui Lim, Ph.D. 

Postdoctoral Associate, Harraz Lab

Maria Noterman, Ph.D.
Postdoctoral Fellow, Nelson Lab

Student Trainees

Elleanor Beaulieu
Undergraduate Student, Herrera Lab

Eva Jessup
Undergraduate Student, Nelson Lab

Clemens Probst
Graduate Student, Nelson Lab

 

 

Publications

Mark T. Nelson, Ph.D.
  1. 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
  2. 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 
  3. 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 
  4. 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
  5. 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.
  1. Lim XR, Harraz OF#.  Mechanosensing by Endothelial Cells, Ann Rev Physiol.  Accepted (# Corresponding author)
  2. 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
  3. 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
  4. 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.
  1. 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
  2. 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
  3. 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
  4. 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.
  1. 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
  2. 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 
  3. 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
  4. Cipolla MJ, Alkayed NJ.  Vascular Biology of Dementia.  Stroke. 2023 Mar; 54(3):  646-647.  doi: 10.1161/STROKEAHA.123.042298.  PMID:  36848429
  5. 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.
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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.
  1. 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
  2. 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
  3. 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      

 

History

Mr. Ray W. Totman, a businessman from Malone, NY, established a foundation that would benefit medical schools in the New England area, particularly UVM in the mid-80s with net assets of $2-$3M.  Mr. Totman was an oil distributor and owned several gas stations in Malone.  He and his wife had no children.  Mr. Totman was disabled and he wanted his estate to be used to further medical research and to find solutions for health problems, particularly stroke research.

Mr. Totman died in 1988, and in the fall of that same year, UVM learned that $150,000 was bequeathed to the College of Medicine with the possibility of additional funds with proper proposals.  All gifts were to be exclusively devoted to scientific or medical research in areas such as cancer, heart disease or any other disease his trustees might select.  In his will, Mr. Totman singled out UVM as one of four institutions that would benefit from his foundation.

The first gift to UVM was received in August 1989 in the amount of $250,000.  At that time, UVM established the "Ray W. Totman and Ildah Totman Medical Research Fund".  The money was used to "construct, equip and operate a laboratory for scientific and medical research concerning Ischemic Cerebrovascular Disease".  The Totman Lab was established in the Department of Pharmacology, under Dr. John Bevan, Chair, and Dr. Rosemary Bevan.  Since 1996 it has been under the supervision of Dr. Mark T. Nelson, Chair of the Department of Pharmacology.

The Totman Foundation contributions totaling over $4.25 million as of 2017, have enabled Dr. Nelson and his colleagues to make significant scientific discoveries in cerebrovascular research that have been published in esteemed journals and have received international recognition.  This recognition has helped our researchers to secure significant funding from the NIH and international sources.

The following is a list of the Trustees and their years of service.

William Herron          1988-1993

Marguerite Boyer       1988-1995

Donald E. Stone        1988-2014

Robert G. Main, Jr.    1993-1998 

Jeffrey Stone            1995-present

Arlene Howard          1998-2023

Donald Stone, Jr.      2014-present

Donald Howard         2023-present

The following is a list of Deans of the UVM College of Medicine and their service during the Totman Foundation relationship.

William Hossfeld Luginbuhl   1970-1991 

John W. Frymoyer               1991-2000

Joseph B. Warshaw             2000-2003

John N. Evans                    2004-2006

Frederick C. Morin III         2007-2018

Richard L. Page                 2018-present