Eva C. Guinan, MD
Professor of Pediatrics, Harvard Medical School
Center/ProgramPediatric Cancer Survivorship
Office phone: 617-632-4932
Preferred contact method: email
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Hematopoietic stem cell transplantation, Bone marrow failure disorders, Aplastic anemia, Myelodysplasia, Regimen-related toxicity
Area of ResearchInduction of Anergy by Costimulatory Blockade
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
BiographyDr. Guinan received her MD from Harvard Medical School in 1980, followed by a pediatric residency at Children's Hospital and a pediatric hematology-oncology fellowship at Children's Hospital and DFCI. She was appointed associate director of the Bone Marrow Transplant Service in 1990 and directed the program from 1997 through 2005. She assumed a new position in 2005 as the Associate Director of the Center for Clinical and Translational Research. Her own translational research program focuses on the costimulatory blockade as a mechanism of overcoming problems related to allogenicity in transplantation and the amelioration of regimen-related toxicity.
- Distinguished Service Award from the Fanconi Anemia Research Foundation, 2009
- Clare and Richard Morse Research Award, 2000
- Clinical Translational Scientist Award, Burroughs Wellcome, 1999
ResearchInduction of Anergy by Costimulatory Blockade
Our research focuses on overcoming problems related to allogenicity in transplantation.
Allogeneic transplantation is limited, in large part, by the ability to find donors of suitable histocompatibility. Global immunosuppression has been an incomplete and highly toxic approach to this problem. Current understanding of T cell activation suggests that blocking B7-CD28 interactions of the costimulatory pathway for human T helper cells may provide both antigen-specific T cell hyporesponsiveness and active suppression of alloantigen specific immunity. We are applying these various strategies to the transplant setting and investigating other approaches to improve immunity after transplantation.
Another area of active investigation is the mitigation of regimen-related toxicity during transplantation and/or chemotherapy. We are investigating novel agents for prevention or treatment of regimen-related toxicity, with a focus on mitigating radiation toxicity.
In another area of investigation, we are examining the role of distributed problem solving techniques in generating, evaluating and maintaining innovation in healthcare related research.
- Duggan C, Bechard L, Donovan K, Vangel M, O'Leary A, Holmes C, Lehmann L, Guinan E. Changes in resting energy expenditure among children undergoing allogeneic stem cell transplantation. Am J Clin Nutr 2003;78:104-9.
- Levy O, Teixeira-Pinto A, White ML, Carroll SF, Lehmann L, Wypij D, Guinan E. Endotoxemia and elevation of lipopolysaccharide-binding protein after hematopoietic stem cell transplantation. Pediatr Infect Dis J 2003;22:978-81.
- Thornley I, Lehmann LE, Sung L, Holmes C, Spear JM, Brennan L, Vangel M, Bechard LJ, Richardson P, Duggan C, Guinan EC. A multiagent strategy to decrease regimen-related toxicity in children undergoing allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2004;10:635-44.
- Bourquin JP, Thornley I, Neuberg D, Brennan L, Kung A, Clark J, Lehmann L, Guinan EC. Favorable outcome of allogeneic hematopoietic stem cell transplantation for relapsed or refractory acute promyelocytic leukemia in childhood. Bone Marrow Transplant 2004;34:795-8.
- Haining WN, Evans JW, Seth NP, Callaway GD, Wucherpfennig KW, Nadler LM, Guinan EC. Measuring T cell immunity to influenza vaccination in children after haemopoietic stem cell transplantation. Br J Haematol 2004;127:322-5.
- Haining WN, Cardoso AA, Keczkemethy HL, Fleming M, Neuberg D, D'Angelo DJ, Stone RM, Galinsky I, Silverman LB, Sallan SE, Nadler LM, Guinan EC. Failure to define window of time for autologous tumor vaccination in patients with newly diagnosed or relapsed acute lymphoblastic leukemia. Exp Hematol 2005;33:286-94.
- Antin JH, Guinan EC, Avigan D, Soiffer RJ, Joyce RM, Martin VJ, Molrine DC. Protective antibody responses to pneumococcal conjugate vaccine after autologous hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005;11:213-22.
- Davies JK, Guinan EC. An update on the management of severe idiopathic aplastic anemia in children. Br J Haem 2007; 136(4): 549-64.
- Davies JK, Gribben JG, Brennan LL, Yuk D, Nadler LM, Guinan EC. Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of two phase I studies. Blood 2008; 112(6): 2232-41.
- Davies JK, Yuk D, Nadler LM, Guinan EC. Induction of alloanergy in human donor T cells without loss of pathogen or tumor immunity. Transplantation 2008; 86(6): 854-64.
- Davies JK, Nadler LM, Guinan EC. Expansion of allospecific regulatory T cells after anergized mismatched bone marrow transplantation. Sci Transl Med 2009; 1(1): 1ra3.
- Richardson PG, Soiffer RJ, Antin JH, Uno H, Jin Z, Kurtzberg J, Martin PL, Steinbach G, Murray KF, Vogelsang GB, Chen AR, Krishnan A, Kernan NA, Avigan DE, Spitzer TR, Shulman HM, Di Salvo DN, Revta C, Warren D, Momtaz P, Bradwin G, Wei LJ, Iacobelli M, McDonald GB, Guinan EC. Defibrotide for the treatment of severe hepatic veno-occlusive disease and multi-organ failure post stem cell transplantation: a multi-center, randomized, dose-finding trial. Biol Blood Marrow Transplant (in press).
- Davies, Jeff