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. - Vienna, 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 Pharmacologyand Surgery (Division of Neurosurgery)

Marilyn J. Cipolla, Ph.D. Professor, Departments of Neurology, Obstetrics & Gynecology, and Pharmacology

Wolfgang R. Dostmann, Ph.D. Professor, Departments of Pharmacology and Molecular Physiology & Biophysics

Kalev Freeman, M.D., Ph.D., Assistant Professor, Department of Surgery, Assistant Professor, Pharmacology

Adrian D. Bonev, Ph.D. Research Assistant Professor, Department of Pharmacology

Daniel M. Collier, Ph.D.  Research Assistant Professor, Department of Pharmacology

Albert L. Gonzales, Ph.D.  Research 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

David Hill-Eubanks, Ph.D. Research Assistant Professor, Department of Pharmacology

Fabrice Dabertrand, Ph.D. Research Assistant Professor, Department of Pharmacology

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

Thomas A. Longden, Ph.D., Research Assistant Professor, Department of Pharmacology

Nathan R. Tykocki, Ph.D. Research Assistant Professor, Department of Pharmacology

Research Technical Support

Hannah Ferris
Research Technician, Wellman Laboratory 

Gaelin Kopec-Belliveau
Research Technician, Nelson Laboratory

Amanda Mirando
Research Technician, Nelson Laboratory 

Maxwell Ross
Research Technician, Nelson Laboratory

Jessica Sheehe
Research Technician, Dostmann Laboratory

Julie Sweet
Senior Research Technician, Cipolla Laboratory

Amelia Zdorove 
Research Technician, Nelson Laboratory

Post-Doctoral Trainees

Osama Harraz, Ph.D.
Postdoctoral Associate, Nelson Laboratory

Nuria Villalba Isabel, Ph.D.
Postdoctoral Associate, Freeman Laboratories

Student Trainees

Daniela Garcia Lustosa
Graduate Student, Nelson Lab

Jessica Sheehe
Graduate Student, Dostmann Lab

2015 Totman Lecturer

David Kleinfeld, Ph.D.
Distinguished Professor, Experimental Biophysics Endowed Chair, University of California at San Diego, CA

2014 Totman Lecturer

J. Kevin Foskett, Ph.D.
Professor and Chair, Department of Physiology, University of Pennsylvania, Philadelphia, PA

Publications

Mark T. Nelson, Ph.D.

1. *Hawkins VE, Takakura AC, Trinh A, Malteiros-Lima MR, Cleary CM, Wenker IC, Dubreuil T, Rodriguez EM, Nelson MT, Moreira TS, Mulkey DK.  Purinergic regulation of vascular tone in the retrotrapezoid nucleus is specialized to support the drive to breathe.  Elife.  2017 Apr 6:  6.  doi:  10.7554/eLife.25232.  PMID:  28387198

2. *Longden TA, Dabertrand F, Koide M, Gonzales AL, Tykocki NR, Brayden JE, Hill-Eubanks DC, Nelson MT.  Capillary K+-sensing initiates retrograde hyperpolarization to increase local blood flow.  Nat Neurosci.  2017 May; 20(5):  717-726. Journal cover. doi:  101113/JP272148.  PMID:  28319610, PMCID:  PMC5404963

3. *Khavandi K, Baylie RA, Sugden SA, Ahmed M, Csato V, Eaton P, Hill-Eubanks DC, Bonev AD, Nelson MT, Greenstein AS.   Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels.  doi:  10.1126/scisignal.aaf6625.  PMID:  27729550, PMCID:  PMC5154376.  Editorial Science Signaling Focus (Hill MA and Braun AP).  Oxidant signaling underlies PKGIa modulation of Ca2+ sparks and Bkca in myogenically active arterioles.  Sci Signal. 9, fs15(2016), featured in the same issue.

4. *Dalsgaard T, Sonkusare SK, Teuscher C, Poynter ME, Nelson MT.  Pharmacological inhibitors of TRPV4 channels reduce cytokine production, restore endothelial function and increase survival in septic mice.  Sci Rep.  2016 Sept 22;  6:  33841.  doi:  10.1038/srep33841.  PMID:  27653046, PMCID:  PMC5031985

5. *Capone C, Dabertrand F, Baron-Menguy C, Charlaris A, Ghezali L, Domenga-Denier V, Schmidt S, Huneau C, Rose-John S, Nelson MT, Joutel A. Mechanistic insights into a TIMP3-sensitive pathway constitutively engaged in the regulation of cerebral hemodynamics.  Elife.  2016 Aug 1: 5.  doi:  10.7554/eLife.17536.  PMID: 27476853, PMCID:  PMC4993587 

6. *Mah W, Sonkusare SK, Wang T, Azeddine B, Pupavac M, Carrot-Zhang J, Hong K, Majewski J, Harvey EJ, Russel L, Chalk C, Rosenblatt DS, Nelson MT, Séguin C.  Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head.  J Med Genet.  2016 Oct:  53(10):  705-709.  doi:  10.1136/jmedgenet-2016-103829.  PMID:  27330106, PMCID:  PMC5035228

George C. Wellman, Ph.D.

1. *Syed AU, Koide M, Brayden JE, Wellman GC.  Tonic regulation of middle meningeal artery (MMA) diameter by ATP-sensitive potassium channels.  J Cereb Blood Flow Metab.  (Submitted May 16, 2017)

2. *Wang F, Koide M, Wellman GC. Nifedipine inhibition of high-voltage activated calcium channel currents in cerebral artery myocytes is influenced by extracellular divalent cations. Frontiers in Physiology, Vascular Physiology section 8, 2017.  PMID:  28439241

3. *Balbi M, Koide M, Wellman GC, Plesnila N.  Inversion of neurovascular coupling after subarachnoid hemorrhage in vivo.  J Cereb Blood Flow Metab.  2017 (E-pub ahead of print)  PMID:  28112024

4. *Balbi M, Koide M, Wellman GC, PLesnila N.  Acute changes in neurovascular reactivity after subarachnoid hemorrhage in vivo.  J Cereb Blood Flow Metab. 2017; 37:  178-187. PMID: 26676226

5. *Pappas AC, Koide M, Wellman GC. Purinergic signaling triggers endfoot high-amplitude Ca2+ signals and causes inversion of neurovascular coupling after subarachnoid hemorrhage.  J Cereb Blood Flow Metab.  36: 1901-1912. 2016.  PMID:  27207166

Book Chapter

1. *Syed A, Koide M, Braas KM, May V, Wellman GC.  PACAP regulation of vascular tone:  differential mechanisms among vascular beds.  In:  Reglodi and Tamas (Eds).  The PACAP Handbook  New York, Springer (In Press)

Marilyn J. Cipolla, Ph.D.

1. *Bosetti F, Galis Z, Bynoe M, Charette M, Cipolla MJ, del Zoppo G, Gould D, Hatsukami T, Jones T, Koenig J, Lutty G, Maric-Balkan C, Stevens T, Tolunay E, Koroshetz W, Gibbons G. Small blood vessels:  Big health problems?:  Scientific Recommendations of the NIH workshop.  JAHA 5(11).  doi:  10.1161/JAHA.116.004389 PMID:  27815267 

2. *Johnson AC, Cipolla MJ.  Altered hippocampal arteriole structure and function in a rat model of preeclampsia:  Potential role in impaired seizure-induced hyperemia.  J Cerebr Blood Flow Metab.  (2016)

3.  *Cipolla MJ, Linfante I, Abuchowski A, Jubin R, Chan S-L. Pharmacologically increasing collateral perfusion during acute stroke using carboxyhemoglobin gas transfer agent (Sanguiate TM) in spontaneously hypertensive rats.  J Cerebr Blood Flow Metab. 2017 (In Press) 

4.  *Cipolla MJ, Biller J.  Persistent brain injury after preeclampsia.  Neurology 2017 (In Press)

5.  *Bosetti F, Koenig J, Ayata C, Back S, Becker K, Broderick J, Carmichael ST, Cho S, Cipolla MJ, et al.  Translational stroke research:  Vision and opportunities.  Stroke 2017 (In Press) 

6.  *Chan S-L, Cipolla MJ. Treatment with low dose fasudil for acute ischemic stroke in chronic hypertension.  J Cerebr Blood Flow Metab. 2017  (In Press) 

Wolfgang R. Dostmann, Ph.D.

1. *Lee DI, Zhu G, Sasaki T, Cho GS, Hamdani N, Holewinski R, Jo SH, Danner T, Zhang M, Rainer PP, Bedja D, Kirk JA, Ranek MJ, Dostmann WR, Kwon C, Margulies KB, Van Eyk JE, Paulus WJ, Takimoto E, Kass DA. Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease. Nature. 2015 Mar 26; 519(7544): 472-476. PMID: 25799991, PMCID: PMC4376609

2.  *Arora K, Sinha C, Zhang W, Moon CS, Ren A, Yarlagadda S, Dostmann WR.  Adebiyi A, Haberman, Y, Denson LA, Wang Z, Naren AP.  Altered cGMP dynamics at the plasma membrane contribute to diarrhea in ulcerative colitis.  Am J Pathol.  2015 Oct;  185(10):  2790-2804.  PMID:  26261085

3. *Moon TM, Tykocki NR, Sheehe JL, Osborne BW, Tegge W, Brayden JE, Dostmann WR.  Synthetic Peptides as cGMP-Independent Activators of cGMP-Dependent Protein Kinase 1a.  Chem Biol. 2015

Kalev Freeman, M.D.

1. *Villalba N, Sakheim AM, Nunez IA, Hill-Eubanks DC, Nelson MT, Wellman GC, Freeman K. Traumatic Brain Injury Causes Endothelial Dysfunction in the Systemic Microcirculation through Arginase-1-Dependent Uncoupling of Endothelial Nitric Oxide Synthase. J Neurotrauma. 2017 Jan 1; 34(1):  192-203.  Journal cover.  PMID:  26757855, PMCID:  PMC5198065

2. *Sackheim AM, Stockwell D, Villalba N, Haines L, Scott CL, Russell S, Hammack SE, Freeman K.  Traumatic brain injury impairs sensorimotor function in mice.  J Surg Res.  E-pub Feb 23, 2017.  Vol. 213, p 100-109. 

3. Curran EJ, Wolfson DL, Watts R, Freeman K.  Cold Blooded:  Evaluating Brain Temperature by MRI During Surface Cooling of Human Subjects.  Neurocrit Care.  2017 Mar 28.  PMID:  28352966 

4. Preston K, Dreyfus N, Harm S, Villalba N, Freeman K.  Packed Red Blood Cells Accumulate Oxidative Stress With Increased Storage Duration.  Shock (E-published June 6, 2017)

5. Thomas AW, Watts R, Filippi CG, Nickerson JP, Andrews T, Lieberman G, Naylor MR, Eppstein MJ, Freeman K.  Dynamic Changes in Diffusion Measures Improve Sensitivity in Identifying Patients with Mild Traumatic Brain Injury.  PLOS One (Accepted June 2017)

*Totman Medical Research Fund Acknowledged

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-present