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

Ms. Arlene Howard - Malone, NY

Mr. Donald Stone Jr. - Fairfax, VA

Mr. Jeffrey Stone - Waterford, NY

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

Gordon Jensen, M.D., 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

Masayo Koide, Ph.D., Research Assistant Professor, Department of Pharmacology

Amreen Mughal, Ph.D., Research Assistant Professor, Department of Pharmacology

Adam Greenstein, MD, Ph.D., Guest Faculty

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Research Technical Support

Daniel Enders
Research Technician, Nelson Laboratory

Hannah Ferris
Research Technician, Wellman Laboratory 

Michael Ippolito
Research Technician, Harraz Laboratory

Curtis Plante
Research Technician, Harraz Laboratory

Adrian Sackheim
Research Technician, Freeman Laboratory

Camila Salcedo
Research Technician, Wellman Laboratory

Sarah Tremble
Senior Research Technician, Cipolla Laboratory

Theresa Wellman 
Senior Research Technician, Nelson Laboratory

Post-Doctoral Trainees

Nicholas Klug, Ph.D.
Postdoctoral Fellow, Nelson Laboratory

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

Student Trainees

Amanda Arnold
Undergraduate Student, Nelson Lab

Elleanor Beaulieu
Undergraduate Student, Herrera Lab

Alexandra Dunstan
Undergraduate Student, Nelson Lab

Valerie Burke
Graduate Student, Wellman Lab

Hannah Fallon
Undergraduate Student, Herrera Lab

Eva Jessup
Undergraduate Student, Nelson Lab

Eleni Karabesini
Graduate Student, Nelson Lab

Hannah Keavany
Undergraduate Student, Wellman Lab

Rachel Petrone
Graduate Student, Nelson Lab

Clemens Probst
Graduate Student, Nelson Lab

Nicolas Sousa
Undergraduate Student, Nelson Lab

Nathan Stine
Undergraduate Student, Wellman Lab

 

Publications

Mark T. Nelson, Ph.D.
  1. 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. Epublished 2022, June.

     

  2. Oka F, Lee JH, Yuzawa I, Li M, von Bornstaedt D, Eikermann-Haetrer K, Qin T, Chung DY, Sadeghian H, Seidel JL, Imai T, Vuralli D, Platt RM, Nelson MT, Joutel A, Sakadzic S, Ayata C.  CADASIL mutations sensitize the brain to ischemia via spreading depolarizations and abnormal extracellular potassium homeostasis.  J Clin Invest.  2022 Apr 15; 132(8): e149759.  doi: 10.1172/JCI149759, PMID:  35202003, PMCID:  PMC9012276

     

  3. Sancho M, Klug NR, Mughal A, Koide M, Huerta de la Cruz S, Heppner TJ, Bonev AD, Hill-Eubanks D, 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

     

  4. Klug NR, Nelson MT. Enhanced Vascular Contractility Following Secondhand Smoke Exposure:  A Pathological “Double-Hit” to Critical Smooth Muscle Ion Channels.  Function (Oxf).  2021 Nov 11; 3(1): zqab061.  doi:  10.1093/function/zqab061. eCollection 2022.  PMID:  35330927

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Osama F. Harraz, Ph.D.
  1. Harraz OF#, Klug NR, Senatore AJ, Hill-Eubanks DC, Nelson MT. Piezo1 Is a Mechanosensor Channel in Central Nervous System Capillaries.  Circ Res. 2022 May 13;   130(10):  1531-1546.  doi:  10.1161/CIRCRESAH.122.320827.  PMID:  35382561, PMCID:  PMC9106929.  Featured article on the Cover.  Accompanied with a Commentary (Cudmore & Santana).  # Corresponding Author.

     

  2. Harraz OF#, Jensen LJ.  Vascular calcium signaling and ageing.  J Physiol. 2021 Dec;  599(24):  5361-5377.  doi:  10.1113/JP280950. PMID:  34705288, PMCID:   PMC9002240.  The 2021 Editor’s Choice List.  # Corresponding Author.

     

  3. Koide M, Harraz OF, Dabertrand F, Longden TA, Ferris HR, Wellman GC, Hill-Eubanks D, Greenstein AS, Nelson MT. Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel diseases.  J Clin Invest. 2021 Sep 15;  131(18): e149029.  doi: 10.1172/JCI149029. PMID:  34351870, PMCID:  PMC8439604.  Accompanied with News Release, and a Commentary (Faraci; JCI 2021).

     

  4. Longden TA*, Mughal A*, Hennig GW, Harraz OF, Shui B, Lee FK, Lee JC, Reining S, Kotlikoff MI, König GM, Kostenis E, Hill-Eubanks D, Nelson MT.  Local IP3 receptor-mediated Ca2+ signals compound to direct blood flow in brain capillaries.  Sci Adv. 2021 Jul 21; 7(30):  eabh0101s.  doi: 10.1126/sciadv.abh0101.  PMID:  34290098, PMCID:  PMC8294755.  * Co-first authors.  Accompanied with News Release.

     

  5. Betrie AH, Brock JA, Harraz OF, Bush AI, He GW, Nelson MT, Angus JA, Write CE, Ayton S.  Zinc drives vasorelaxation by acting in sensory nerves, endothelium and smooth muscle.  Nat Commun. 2021 Jun 1; 12(1):  3296.  doi:  10.1037/s41467-021-23198-6. PMID:  34075043, PMCID:  PMC8169932.  Accompanied with News Release.

     

  6. Dabertrand F*, Harraz OF*, Koide M, Longden TA, Rosehart AC, Hill-Eubanks DC, Joutel A, Nelson MT.  PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity.  Proc Natl Acad Sci USA. 2021 Apr 27; 118(17):  e2025998118. doi: 10.1073/pnas.2025998118. PMID: 33875602, PMCID:  PMC8092380.   *Co-first authors.  Accompanied with a Commentary (Earley and Kleinfeld, PNAS 2021).

     

  7. Sackheim AM, Villalba N, Sancho M, Harraz OF, Bonev AD, D’Alessandro A, Nemkov T, Nelson MT, Freeman K.  Traumatic brain injury impairs systemic vascular function through disruption of inward-rectifier potassium channels.  Function (Oxf). 2021; 2(3): zqab018.  doi:  10.1093/function/zab018.  PMID:  34568829, PMCID:  PMC8462507.  Accompanied with a Commentary (Weir and Longden, Function 2021).

     

  8. Mughal A*, Harraz OF*, Gonzales AL, Hill-Eubanks D, Nelson MT.  PIP2 improves cerebral blood flow in a mouse model of Alzheimer’s disease.  Function (Oxf). 2021 Feb 22 2(2): zqab010  doi:  10.1093/function/zqab010.eCollection 2021. PMID:  33763649, PMCID:  PMC7955025. *Co-first authors.  Accompanied with an editorial (Jackson, Function 2021), a Commentary (Fan & Roman, Geroscience 2021), and the Cover of the May issue of Function.
George C. Wellman, Ph.D.
  1. 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.

Marilyn J. Cipolla, Ph.D.
  1. Li Z and Cipolla MJ. Mechanisms of Flow-Mediated Dilation of Pial Collaterals and the Effect of Hypertension.  Hypertension. 2022 Feb; 79(2): 457-467 doi:  10.1161/HYPERTENSIONAHA.121.18602.  PMID:  34856815, PMCID:  PMC8755599. 

     

  2. Cipolla MJ, Tremble ST, DeLance N, Allison D, Johnson AC (2021). Treatment with apocynin selectively restores hippocampal arteriole function and seizure-induced hyperemia in a model of preeclampsia.  J Cerebral Blood Flow Metab.  2022 Feb 9:  221678X221080092.  doi:  10.1177/0271678X221080092.  PMID:  35137612.

      

  3. Cipolla MJ.  Therapeutic Induction of Collateral Flow.  Transl Stroke Res.  2022 Apr 13.  doi: 10.1007/s12975-022-01019-2.  PMID:  35416577.


  4. Johnson AC, Tremble SM, Cipolla MJ.  Experimental Preeclampsia Causes Long-Lasting Hippocampal Vascular Dysfunction and Memory Impairment.  Front Physiol.  2022 May 9; 13:889918.  doi: 10.3389/fphys.2022.889918.eCollection 2022. PMID:  35615682, PMCID:  PMC9124928.

     

  5. Whitaker EE, Johnson AC, Tremble SM, McGinn C, DeLance N, and Cipolla MJ. Cerebral blood flow autoregulation in offspring from experimentally preeclamptic rats and the effect of age. Front Physiol  2022 (In Press).

     

  6. Alkyed N and Cipolla MJ.  Role of Endothelial Cells and Platelets in COVID-Related Cerebrovascular Events. Stroke.  2022 Jun 8:  101161STROKEAHA122039971.  doi:  10.1161/STROKEAHA.122.039971.  PMID:  35674044. 


Kalev Freeman, M.D.
  1. Bouchard BA, Colovos C, Lawson MA, Osborn ZT, Sackheim AM, Mould KJ, Janssen WJ, Cohen MJ, Majumdar D, Freeman K.  Increased histone-DNA complexes and endothelial-dependent thrombin generation in severe COVID-19.  Vascul Pharmacol.  2022 Feb; 142: 106950.  doi 10.1016/j.vph.2021.106950.  PMID:  34871770, PMCID:  PMC8641427

     

  2. Kamin Mukaz D, Gergi M, Koh I, Zakai NA, Judd SE, Sholzberg M, Baumann Kreuziger L, Freeman K, Colovos C, Olson NC, Cushman M.  Thrombo-Inflammatory biomarkers and D-dimer in biracial cohort study.  Res Pract Thromb Haemost.  2021 Dec 7; 5(8):  e12632.  doi:  10.1002/rth2.12632.eCollection 2021 Dec.  PMID:  34934895, PMCID:  PMC8652130

     

  3. 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 Jun 10.  doi:  10.1097/TA.0000000000003723. PMID:  35687811

     

  4. Villalba N, Sackheim AM, Lawson MA, Haines L, Chen Y, Sonkusare SK, Ma Y, Li J, Majumdar D, Bouchard BA, Boyson JE, Poynter ME, Nelson MT, Freeman K.  The polyanionic drug suramin neutralizes histones and prevents endotheliopathy.  Bio Rxiv 2021.12.09.469611; doi:  10.1101/2021.12.09.469611 (In Review, American Journal of Physiology Lung Physiology)

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Adam S. Greenstein, M.D., Ph.D.
  1. Muratoglu SC, Charette MF, Galis ZF, Greenstein AS, Daugherty A, Joutel A, Kozel BA, Wilcock DM, Collins EC, Sorond FA, Howell GR, Hyacinth HI, Lloyd KKC, Stenmark KR, Boehm M, Kahn ML, Corriveau R, Wells S, Bussey TJ, Sukoff Rizzo SJ, Iruela-Arispe ML.  Perspectives on Cognitive Phenotypes and Models of Vascular Disease.  Arterioscler Thromb Vasc Biol.  2022 May 5;  101161ATVBAHA122317395 doi:  10.1161/ATVBAHA.122.317395.  PMID:  35510549

     

  2. Evans LE, Taylor JL, Smith CJ, Pritchard HAT, Greenstein AS, Allan SM.  Cardiovascular comorbidities, inflammation, and cerebral small vessel disease.  Cardiovas Res.  2021 Nov 22; 117(13): 2575-2588.  doi:  10.1093/cvr/cvab284.  PMID:  34499123

     

  3. 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

 

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-present

Donald Stone, Jr.      2014-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