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Thomas J. Macvittie, PhD

Academic Title:

Professor

Primary Appointment:

Radiation Oncology

Secondary Appointment(s):

Veterinary, Pathology

Location:

MSTF, 634-E

Phone (Primary):

(410) 706-5255

Phone (Secondary):

(410) 706-5274

Fax:

(410) 706-5270

Education and Training

 

Biology, Alfred University, BS, Biology

 

State University of New York, MS, Natural Sciences/Radiation Biophysics

 

State University of New York, PhD, Radiation Biology

Biosketch

Dr. MacVittie, is recognized internationally as an expert on the effects of radiation on the hematopoietic and gastrointestinal systems in large animal models and their treatment, in vivo, with supportive care and selected organ-specific medical countermeasures against acute and delayed effects of acute radiation exposure.                        

He earned M.S. and Ph.D. degrees in radiation biology at the State University of New York (SUNY) at Buffalo and has more than 40 years of experience as a radiobiologist in the field of experimental hematology.  He has published 184 peer-reviewed manuscripts and 47 chapters in books or proceedings.  He has co-edited 5 books published from international meetings organized on radiation effects and treatment of the ARS. 

 Dr. MacVittie has served as an advisor to the WHO Collaborating Centers in Radiation Emergency Medical Preparedness and Assistance and as a member of NATO Radiation Research Study groups. He was a member of a Task Group for the International Council on Radiation Protection entitled “Radiation Effects on Normal Tissue”, the CDC Strategic National Stockpile Radiation Working Group, the American Society of Hematology, the International Society of Experimental Hematology and Radiation Research. Dr. MacVittie has served on the editorial board of the journal Experimental Hematology and is currently a member of the editorial board of the journal Stem Cells and serves as an ad hoc reviewer for numerous journals and National Institutes of Health and Department of Defense grants and contracts. Dr. MacVittie was invited by the Secretary, U.S. Department of Health and Human Services, to serve on the inaugural National Biodefense Science Board Federal Advisory Committee from 2007 to 2011.

 His early work clearly demonstrated the efficacy of supportive care and hematopoietic growth factors on increasing lineage-specific cell recovery and survival in myelosuppressed and lethally irradiated large animal models. The MacVittie laboratory has the most extensive data base demonstrating the effect of cytokines on enhancing survival and recovery of hematopoiesis after total-body irradiation to include autologous stem cell transplantation and cytokine-induced mobilization of stem cells. The accumulated data base served as the focal point for recent efforts to design the initial “pivotal” trials under the FDA’s “animal rule” to determine the treatment efficacy of neupogen and neulasta to treat potentially lethally irradiated personnel. These are the first two FDA-approved MCM (March and October, 2015) to treat the H-ARS.

 Dr. MacVittie was the principal investigator of the recent sole research contract ($50 million/five years from 2005-2015) awarded by NIAID to assess the efficacy and mechanism of action for Medical Countermeasures Against Radiological Threats (MCART). The MCART consortium had 15 research and administrative components in the United States and England. The MacVittie laboratory has recently developed an Animal Model Research Platform (focused on mouse and nonhuman primates) for the Acute Radiation Syndrome and the Delayed Effects of Acute Radiation Exposure that positions the MacVittie laboratory with the MCART Research Consortium to carry the lead in an integrated effort to develop the best products to treat radiation-induced hematopoietic and gastrointestinal sub-syndromes, immunosuppression, inflammation and lung injury in potentially lethally irradiated personnel.

Research/Clinical Keywords

Radiation effects, acute radiation syndrome, delayed effects of acute radiation exposure, large animal models, medical management, medical countermeasures, FDA animal rule

Highlighted Publications

  1. MacVittie,T.J., Bennett A, Booth C, Tudor G, Garofalo M, Ward A, Shea-Donohue T, Jackson III W. (2012) The prolonged gastrointestinal syndrome in rhesus macaques: The relationship between gastrointestinal, hematopoietic and delayed multi-organ sequelae following acute radiation exposure. J Health Phys. 103(4):427-453.

 

  1. Garofalo, M.C., Bennett, A., Farese, A.M., Ward, A.A., Taylor-Howell, C., Cui, W., Gibbs, A., Lasio, G., Jackson, W., MacVittie, T.J. (2014) The Delayed Pulmonary Syndrome Following Acute High-Dose Irradiation: A rhesus macaque model. J Health Phys 106(1):56-72.

 

  1. Farese, AM, Cohen, MV, Katz, BP, Smith, CP, Gibbs, AM, Cohen, DM, MacVittie, TJ. (2013) Filgrastim    Improves Survival in Lethally Irradiated Nonhuman Primates. Rad Research, 179(1):89-100

Additional Publication Citations

MacVittie, T.J. and Walker, R.I., (1978) Endotoxin-alterations in canine granulopoiesis: Colony-stimulating factor, colony-forming cells in culture, and growth of cells in diffusion chambers.  Exp. Hematol. 6:613-618.

MacVittie, T.J. and Walker, R.I. (1978) Canine granulopoiesis: Alternations induced by suppression of gram-negative flora.  Exp. Hematol. 6:639-647.

MacVittie, T.J. and Walker, R.I. (1980) Hematologic responses induced by endotoxin in normal and tolerant dogs. Exp. Hematol. 8:599-609.

Natanson, C. Fink, M.P., Ballantyne, H.K., MacVittie, T.J., Conklin, J. J., Parrillo, J.E. (1986) Gram negative bacteremia produces both severe systolic and diastolic cardiac dysfunction in a canine model that simulates septic shock.  J. Clin. Invest. 78:259.

Monroy, R.L., MacVittie, T.J., Darden, J.H. Schwartz, G.N. and Patchen, M.L. (1986) The Rhesus Monkey: A primate model for hemopoietic stem cell studies.  Exp. Hematol. 14:904-911.

Monroy, R.L., Vriesendorp, H.M., MacVittie, T.J., (1987) Improved survival of dogs exposed to fission neutron irradiation and transplanted with DLA identical bone marrow.  Bone Marrow Transplantation, 2:375-384.

Monroy, R.L., Skelly, R.R., Taylor, P., Dubois, A., Donahue, R.E., MacVittie, T.J. (1988) Recovery from severe hemopoietic suppression using recombinant human granulocyte-macrophage colony stimulating factor.  Exp. Hematol. 16:334-348.

MacVittie, T.J., Monroy, R.L., Patchen, M.L. Souza, L.M., (1990) Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole body irradiation. Intl. J. Radiat. Biol. 57:723-736.

MacVittie, T.J., Monroy, R., Vigneulle, R.M., Zeman, G.H., Jackson, W.E. (1991) The relative biological effectiveness of mixed fission-neutron gamma radiation on the hematopoietic syndrome in the canine: Effect of therapy on survival.  Rad. Research. 128:S29-36.

Hematopoietic  cytokines, in vivo efficacy in NHP model:  I continued our focus on developing reliable and well-characterized models of the ARS. Our lab was instrumental in assessing the efficacy of multiple cytokines and growth factors destined for clinical trials.

Williams, D.E., Farese, A.M., Dunn, J., Park, L.S., Frieden, E., Seiler, MacVittie, T.J. (1993) A GM-CSF/IL-3 fusion protein promotes neutrophil and platelet recovery in sublethally irradiated rhesus monkeys.  Biotechnology Therapeutics. 4:17-29.

Farese, A.M., Williams, D.E., Seiler, F.R., MacVittie, T.J. (1993) Combination protocols of cytokine therapy with interleukin-3 and granulocyte macrophage-colony stimulating factor, in a primate model of radiation-induced marrow aplasia. Blood 82: 3012-3018.

Farese, A.M., Hunt, P., Grab, L.B., MacVittie, T.J. (1996) Enhancement of hematopoietic reconstitution in nonhuman primates following radiation-induced aplasia by the combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony stimulating factor. J Clin Inves 97:2145-2151.

MacVittie, T.J., Farese, A. M., Smith, W.G., Baum, C. M., Burton, E., McKearn, J. P. (2000) Myelopoietin, an engineered chimeric IL-3 and G-CSF receptor agonist, stimulates multilineage hematopoietic recovery in a nonhuman primate model of radiation-induced myelosuppression. Blood 95:837-845.

Medical management , cytokines and ARS and DEARE models: I then renewed an earlier interest in model development of delayed effects, now collected under the title of delayed effects of acute radiation exposure (DEARE). My lab also continued to assess MCM efficacy in these models with the addition of supportive care. We attempted to mimic the “best” care that would be provided in the context of a radiation nuclear scenario.

Waselenko, J.K., MacVittie, T.J., Blakely, W.F., Pesik, N., Wiley, A. L., Dickerson, W.E., Tsu, H., Conifer, D.L., Coleman, C. N., Seed, T., Lowry, P., Armitage, J.O., Dainiak, N.  (2004) Medical management of acute radiation syndrome: recommendations of the strategic national stockpile radiation working group. Annals of Internal Medicine. Ann Intern Med 140(12):1037-51.

MacVittie TJ, Farese AM, Jackson W 3rd. (2005) Defining the Full Therapeutic Potential of Recombinant Growth Factors in the Post Radiation-Accident Environment: The effect of supportive care plus administration of G-CSF.  J Health Phys. 89(5):546-55..

MacVittie,T.J., Farese, A.M., Bennett A, Gelfond D, Shea-Donohue T, Tudor G, Booth C, McFarland E, Jackson III W. (2012) The acute gastrointestinal sub-syndrome of the acute radiation syndrome: A rhesus macaque model. J Health Phys. 103(4):411-426. 

A strategic approach: ARS and DEARE. Most recently we have emphasized the link between the ARS and DEARE and have proposed a more strategic view of radiation injury and treatment that includes multiple organ injury. We focus on the concurrent evolution of the ARS and DEARE and have developed models in the nonhuman primate to assess the efficacy of medical countermeasures (MCM) specific for ARS or DEARE sequelae but also to determine the effect of MCM on other organ systems. Our recently developed animal model research platform will permit an informed strategic view of the efficacy of MCM relative to the complex interaction of multi-organ organ-specific effects.

MacVittie,T.J., Bennett A, Booth C, Tudor G, Garofalo M, Ward A, Shea-Donohue T, Jackson III W. (2012) The prolonged gastrointestinal syndrome in rhesus macaques: The relationship between gastrointestinal, hematopoietic and delayed multi-organ sequelae following acute radiation exposure. J Health Phys. 103(4):427-453.

Garofalo, M.C., Bennett, A., Farese, A.M., Ward, A.A., Taylor-Howell, C., Cui, W., Gibbs, A., Lasio, G., Jackson, W., MacVittie, T.J. (2014) The Delayed Pulmonary Syndrome Following Acute High-Dose Irradiation: A rhesus macaque model. J Health Phys 106(1):56-72.

ARS: pivotal trials under the FDA AR. Our research teams conducted two GLP-compliant trials in the NHP under the criteria of the FDA “Animal rule” (AR), that document the treatment efficacy of neupogen or neulasta to mitigate the lethal effects of total-body irradiation. The neupogen and neulasta studies formed the basis for FDA approval of as the first and second drugs (March, 2015, November 2015) under the FDA AR to treat personnel exposed to potentially lethal, myelosuppressive doses of radiation.

Farese, AM, Cohen, MV, Katz, BP, Smith, CP, Gibbs, AM, Cohen, DM, MacVittie, TJ. (2013) Filgrastim    Improves Survival in Lethally Irradiated Nonhuman Primates. Rad Research, 179(1):89-100

Hankey, K.G., Farese A.M., Blaauw, E.C., Gibbs, A.M., Smith, C.P., Katz, B.P., Tong, Y., Prado, K.L.,MacVittie, T.J. (2015) Pegfilgrastim Improves Survival of Lethally Irradiated Nonhuman Primates. Rad Research 183(6): 643-655.

A strategic approach to radiation effects and treatment. I have organized three complete issues of the Health Physics Journal (2012, 2014, 2015) that described the evolving development of the NIAID-sponsored Consortium, We have emphasized the linkage of tactical and strategic approaches to radiation effects, establishment of our animal model research platform and specific Cores such as Radiation Physics, Tissue Imaging, and Multi-Modal Organ Imaging to underscore the value of a more global multi-disciplinary approach to defining radiation effects, mechanism of action and treatment in animal models.

MacVittie, TJ. (2012, 2014, 2015) Organized three Health Physics Journal Issues: Animal Models: The Medical Countermeasures Against Radiological Threats (MCART) Consortium.1. Health Phys 103(4), pp340-483; 2. Health Phys. 106 (1), pp1-134;3. Health Phys. 109(5), pp335-521.

Complete Bibliography:  

http://www.ncbi.nlm.nih.gov/sites/myncbi/thomas.macvittie.1/bibliography/49775882/public/?sort=date&direction=ascending

Grants and Contracts

Ongoing Research Support     

SRI/NIAID #HHSN272201500013I; SRI RFP# DD-052416-1  MacVittie, TJ (PI) 

07/07/2016 to 04/30/2016

Program Title: MCM efficacy in the context of the concurrent development of the ARS- and DEARE-associated morbidity and mortality in a NHP model of partial-body irradiation with marrow sparing. Role: PI

Professional Activity

 

Previous Positions

 

1970-1972        Radiobiologist, United States Army Medical Research Laboratory, Ft. Knox, KY.

 

1972-1976        Research Physiologist, Armed Forces Radiobiology Research Inst. (AFRRI), Bethesda, MD.

 

1976-1982        Chief Hematology Division, Experimental Hematology Dept., AFRRI, Bethesda, MD 20889.

 

1982-1995        Chairman and Project Leader, Experimental Hematology Department, AFRRI, Bethesda, MD.

 

1995-           Professor, University of Maryland School of Medicine, Depts. of Radiation Oncology and  Pathology, Baltimore, MD 

Extramural: Participant, Advisor, Consultant, Member:

WHO: Scientific Advisor, 4th (Ulm, Germany) & 5th (Paris, France) Coordination Meetings of WHO Collaborating Centers in Radiation Emergency Medical Preparedness and Assistance, 1992 - 1994.

Board Member: International Association of Radiopathology, Fontenay-Aux-Roses, France, 1995 - 2002.

Editorial Board, Journal of Experimental Hematology

Editorial Board, The Journal of Stem Cells, 2001 – present

Member, CDC, Strategic National Stockpile Radiation Working Group, 2003-2005

NIH, NIAID, Special Emphasis Panel: Cooperative Research for the Development of Vaccines, Adjuvants, Therapeutics and Diagnostics for Biodefense and SARS.

Ad Hoc Review, Chairperson, Scientific Review Program, “Myeloid Progenitor Cell Therapy for Radiation Exposure”, 2005.

Member ICRP Task Group: “Radiation Effect on Normal Tissues”, 2006 - 2009.

Consultant, Co-Chairperson: “IAEA Radiological Studies of Normal Tissue Effects in the 1-10 Gy Range and Higher, Relevant to Nuclear Accidents and other Radiation Incidents, 2007.

Board Member, Inaugural National Biodefense Science Board, 2007 – 2011.

Committee member: NCRP SC 1-24; NASA: Radiation Exposure in Space and the Potential of CNS Effects. 2016 – present.