Dr. Raimon Duran-Struuck's Research
Allogeneic hematopoietic cell transplantation (allo-HCT) is a powerful therapy for the treatment of many malignant and non-malignant lymphohematopoietic disorders, and is also important for the development of immunological tolerance for solid organ transplantation. The Duran-Struuck laboratory is focused on developing novel reduced intensity allo-HCT and cellular therapies for the establishment of tolerance and for the treatment of malignant and autoimmune disorders. The laboratory works closely with investigators within the CCTI and clinicians from the Columbia Medical Center.
A major effort of the laboratory is currently focused on developing graft-versus host disease (GVHD) free allogeneic bone marrow transplant (BMT) protocols across MHC barriers where in vitro expanded host regulatory T cells are delivered at the time of BMT. This protocol has shown to achieve long-lived mixed chimerism and establishment of immunological tolerance. This was demonstrated by the survival of a donor kidney transplanted months after the original BMT without the cover of immunosuppression. The goal now is to further refine this protocol for use with more immunogenic tissues/organs and to extend this approach to the treatment of hematological malignancies and autoimmune disorders.
The Duran-Struuck laboratory is focused in understanding the immunological factors responsible for tolerance, graft-versus-host (GVH) and host-versus-graft (HVG) responses in clinically relevant large animal models. The ability to manipulate the level of donor chimerism using cellular therapies (such as donor leukocyte infusions) is of major interest. These can help tailor therapies for either solid organ transplantation, or the treatment of autoimmunity diseases and cancer. Many approaches shown to be effective in small animal models such as rodents, have either failed or proven to be too dangerous in the clinic. Thus, studying many of these cell-based approaches in large animals will provide additional confidence the safe transition to the clinical setting.
Because humans and animals are susceptible to fatal viral diseases during the period of immunosuppression, we also are interested in developing regimens that minimize these infections. Cytomegalovirus reactivation, a fatal viral complication often observed in humans, is also encountered in our pre-clinical models, and we are optimizing our studies to minimize/treat CMV.
1. Duran-Struuck R, Tawara I, Lowler K, Clouthier SG, Weisiger E, Rogers C, Luker G, Kumanogoh A, Liu C, Ferrara JL, Reddy P. ”A novel role for the semaphorin Sema4D in the induction of allo-responses”. Biol Blood Marrow Transplant. 2007 Nov;13(11):1294-1303. Epub 2007 Sep 21.
2. Duran-Struuck R, Reddy P. “Biological advances in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation” Transplantation. 2008 Feb 15;85(3):303-8.
3. Duran-Struuck R, Hartigan A, Clouthier SG, Dyson MC, Lowler K, Gatza E, Tawara I, Toubai T, Weisiger E, Hugunin K, Reddy P, Wilkinson JE. “Differential susceptibility of C57BL/6NCr and B6.Cg-Ptprca mice to commensal bacteria after whole body irradiation in translational bone marrow transplant studies”. J Transl Med. 2008 Feb 28;6(1):10
4. Pavan Reddy, Yaping Sun, Tomomi Toubai, Raimon Duran-Struuck, Shawn G. Clouthier, Elizabeth Weisiger, Yoshinobu Maeda, Isao Tawara, Oleg Krijanovski, Erin Gatza, Chen Liu, Chelsea Malter, Paolo Mascagni, Charles A. Dinarello, James L.M. Ferrara." Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase dependent dendritic cell functions and regulates experimental graft-versus-host disease" Journal of Clinical Investigation. 2008
5. Horner BM, Randolph MA, Duran-Struuck R, Hirsh EL, Ferguson KK, Teague AG, Butler PE, Huang CA. “Induction of tolerance to an allogeneic skin flap transplant in a preclinical large animal model”: Transplant Proc. 2009 Mar;41(2):539-41
6. Duran-Struuck R, Dysko RC. “Principles of bone marrow transplantation (BMT): providing optimal veterinary and husbandry care to irradiated mice in BMT studies”. J Am Assoc Lab Anim Sci. 2009 Jan;48(1):11-22.
7. Duran-Struuck R, Cho PS, Teague AG, Fishman B, Fishman AS, Hanekamp JS, Moran SG, Wikiel KJ, Ferguson KK, Lo DP, Duggan M, Arn JS, Billiter B, Horner B, Houser S, Yeap BY, Westmoreland SV, Spitzer TR, McMorrow IM, Sachs DH, Bronson RT, Huang CA. “Myelogenous leukemia in adult inbred MHC-defined miniature swine: a model for human myeloid leukemias”. Vet Immunol Immunopathol. 2010 Jun 15;135(3-4):243-56.
8. Tawara I, Shlomchik WD, Jones A, Zou W, Nieves E, Liu C, Toubai T, Duran-Struuck R, Sun Y, Clouthier SG, Evers R, Lowler KP, Levy RB, Reddy P. “A crucial role for host APCs in the induction of donor CD4+CD25+ regulatory T cell-mediated suppression of experimental graft-versus-host disease”. J Immunol. 2010 Oct 1;185(7):3866-72. Epub 2010 Sep 1
9. Zhirui Wang, Raimon Duran-Struuck, Rebecca Crepeau, Abraham Matar, Isabel Hanekamp, Srimathi Santhanam, David M. Neville Jr., David H. Sachs, Christene A. Huang "Development of a diphtheria toxin based anti-porcine CD3 recombinant immunotoxin”. Bioconjugate Chemistry. 2011
10. Matar AJ, Pathiraja V, Wang Z, Duran-Struuck R, Gusha A, Crepeau R, Tasaki M, Sachs DH, Huang CA. Effect of pre-existing anti-diphtheria toxin antibodies on T cell depletion levels following diphtheria toxin-based recombinant anti-monkey CD3 immunotoxin treatment. Transpl Immunol. 2012 Aug;27(1):52-4
11. Duran-Struuck R, Matar A, Crepeau R, Gusha A, Schenk M, Hanekamp I, Pathiraja V, Spitzer TR, Sachs DH, Huang CA. Lack of antidonor alloantibody does not indicate lack of immune sensitization: studies of graft loss in a haploidentical hematopoietic cell transplantation Swine model. Biol Blood Marrow Transplant. 2012 Nov;18(11):1629-37
12. Crepeau R, Matar A, Spitzer TR, Robson S, Pathiraja V, Sachs DH, Huang CA, Duran-Struuck R. Edema and tetraparesis in a miniature pig after allogeneic hematopoietic cell transplantation. Comp Med. 2012 Aug; 62(4):298-302.
13. Vimukthi Pathiraja, Abraham J. Matar, Ashley Gusha, Christene A. Huang, Raimon Duran-Struuck Development of a Safe Protocol of Leukapheresis for Nonhuman Primates under 10 kilograms. In Press. Journal of the American Association of Laboratory Animal Medicine. February 2013.
14. Abraham J Matar,Rebecca L Crepeau, Vimukthi Pathiraja, Simon Robson, Jay A Fishman, Thomas R Spitzer,David H Sachs, Christene A Huang, and Raimon Duran-Struuck1 .Effects of Mobilization Regimens in Donors on Outcomes of Hematopoietic Cell Transplantation in Miniature Swine. Comparative Medicine. January 2013.
1. John Hanekamp, Raimon Duran-Struuck and David H Sachs. “Transplantation in Miniature Swine” The Mini Pig in Biomedical Research. CRC Press (Taylor & Francis Group). 2011 In press (Book Chapter)
2. M.J. Linn, R. Duran-Struuck, A.K. Trivedi, L.B. Zajic, S.K. Wrobleski , A.E. Hawley and D.D. Myers “Biology and Medicine of Non-human Primates. Part I: Physiology and Management”. In: Laboratory Animal Medicine and Management, Reuter JD and Suckow MA (Eds.) 2006. Publisher: International Veterinary Information Service. Ithaca NY. (www.ivis.org)
3. M.J. Linn, R. Duran-Struuck, A.K. Trivedi, L.B. Zajic, S.K. Wrobleski , A.E. Hawley and D.D. Myers “Biology and Medicine of Non-human Primates. Part II: Clinical Medicine and Uses”. In: Laboratory Animal Medicine and Management, Reuter JD and Suckow MA (Eds.) 2006. Publisher: International Veterinary Information Service. Ithaca NY. (www.ivis.org)