Josef Kurtz

Professor of Biology

The following are topics that will always catch Dr. Kurtz's attention: swimming, bike riding, running, face transplants, dogs, Vermont, the Upper Peninsula, microglia, dancing, camping, Dave Matthews Band, the Patriots, flow cytometry and IF miscroscopy, the Red Sox, time trial bikes, the microbiome, the newest iPhone, and those individuals who have 'grit'.

Since deciding upon a career in biological research, I have always been pulled towards those questions that are complex and cross many different traditional and historical boundaries. As a graduate student and postdoctoral fellow, although my training was as an immunologist, I found myself in the 'messy' fields of transplantation and autoimmunity, asking questions about the nature of tolerance, and how we might manipulate and re-educate the immune system to prevent the rejection of transplanted organs or reverse the state of autoimmunity. In these settings, I used a wide range of tools and techniques, ranging from traditional (PCR, MLR) and relatively new (RNA microarray analysis, confocal microscopy, multicolor (10+) flow cytometry and sorting) molecular and cellular approaches to constructing complex in vivo mouse models with various transgenic, knockout, and congenic strain combinations.

After joining Emmanuel College, Dr. Williams and I created the NeuroImmunology Research Group (NIRP), with the goal of taking each of our specific backgrounds and finding common, fertile ground in which to develop a truly interdisciplinary project to be driven by the undergraduates at the College. Over the past several years, the models and techniques we have developed have provided us not only the preliminary data for grant proposals, but has been presented at peer- reviewed national and international conferences.

In addition to the NIRP group, I hold the title of Clinical Instructor of Surgery (Immunology) at Harvard Medical School, and Assistant Immunologist at the Massachusetts General Hospital in the Transplantation Biology Research Center (TBRC), where I investigate the mechanisms of tolerance induction of vascularized composite allograft transplants (hand and face transplants) through hematopoietic stem cell transplantation using pre-clinical large animal models.

The impact that these projects on the participating undergraduate students has exceeded even my wildest expectations: over the past several years graduates of the NIRP/TBRC group have gained admission to some of the most competitive graduate programs, including Harvard Medical School, Tufts Dental School, Duke University, University College of London, and University of Massachusetts Medical School. The education that the students receive extends significantly beyond learning specific techniques or simple data analysis, as they are actively involved in all steps from literature review and generating hypotheses to experimental design to drawing valid conclusions.

What I Love About Emmanuel:

Emmanuel is a place where one can become the person they aspire to become.

Ph.D., Harvard Medical School; B.S. Massachusetts Institute of Technology

  • BIOL1101 Life on Earth
  • BIOL1106 Introduction to Organismic and Evolutionary Biology
  • BIOL2119 Current Topics in Biology Research
  • BIOL3119 Immunology
  • BIOL3125 Molecular Biology
  • BIOL3135 Cancer Biology
  • BIOL4160 Senior Seminar

Primary Research Articles:

  • Wekerle T, Kurtz J, Ito H, Ronquillo JV, Dong V, Zhao G, Shaffer J, Sayegh MH, Sykes M. Allogeneic bone marrow transplantation with co-stimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment. Nat Med. 2000 Apr;6(4):464-9.
  • Wekerle T, Kurtz J, Sayegh M, Ito H, Wells A, Bensinger S, Shaffer J, Turka L, Sykes M.  Peripheral deletion after bone marrow transplantation with costimulatory blockade has features of both activation-induced cell death and passive cell death. J Immunol. 2001 Feb 15;166(4):2311-6.
  • Kurtz J*, Ito H*, Shaffer J, Sykes M.     *co-first authors
    CD4 T cell-mediated alloresistance to fully MHC-mismatched allogeneic bone marrow engraftment is dependent on CD40-CD40 ligand interactions, and lasting T cell tolerance is induced by bone marrow transplantation with initial blockade of this pathway. J Immunol. 2001 Mar 1;166(5):2970-81.  
  • Kurtz J*, Ito H*, Wekerle T, Shaffer J, Sykes M.  *co-first authors
    Mechanisms involved in the establishment of tolerance through costimulatory blockade and BMT: lack of requirement for CD40L-mediated signaling for tolerance or deletion of donor-reactive CD4+ cells. Am J Transplant. 2001 Nov;1(4):339-49.
  • Blaha P, Bigenzahn S, Koporc Z, Schmid M, Langer F, Selzer E, Bergmeister H, Wrba F, Kurtz J, Kiss C, Roth E, Muehlbacher F, Sykes M, Wekerle T.  The influence of immunosuppressive drugs on tolerance induction through bone marrow transplantation with costimulation blockade. Blood. 2002 Nov 14.
  • Kurtz J, Lie A, Griffith M, Eysaman S, Shaffer J, Anosova N, Turka L, Benichou G, Sykes M.  Lack of a role for CsA-sensitive or Fas pathways in the tolerization of CD4 T cells via BMT and anti-CD40L.  Am J Transplant.  2003 Jul; 3(7): 804-16.
    Takeuchi Y, Ito H, Kurtz J, Wekerle T, Ho L, Sykes M.   Earlier low-dose TBI or DST overcomes CD8+ T-cell-mediated alloresistance to allogeneic marrow in recipients of anti-CD40L. Am J Transplant. 2004 Jan;4(1):31-40.
  • Kurtz J, Shaffer J, Lie A, Anosova N, Benichou G, Sykes M. Mechanisms of early peripheral CD4 T-cell tolerance induction by anti-CD154 monoclonal antibody and allogeneic bone marrow transplantation: evidence for anergy and deletion but not regulatory cells. Blood. 2004 Jun 1;103(11):4336-43. Epub 2004 Feb 12.
  • Domenig C, Sanchez-Fueyo A, Kurtz J, Alexopoulos SP, Mariat C, Sykes M, Strom TB, Zheng XX. Roles of deletion and regulation in creating mixed chimerism and allograft tolerance using a nonlymphoablative irradiation-free protocol. J Immunol. 2005 Jul 1;175(1):51-60.
  • Fehr T, Takeuchi Y, Kurtz J, Wekerle T, Sykes M.  Early regulation of CD8 T cell alloreactivity by CD4+CD25- T cells in recipients of anti-CD154 antibody and allogeneic BMT is followed by rapid peripheral deletion of donor-reactive CD8+ T cells, precluding a role for sustained regulation. Eur J Immunol. 2005 Sep;35(9):2679-90.
  • Camirand G, Stephan L, Rousseau J, Sackett MK, Caron NJ, Mills P, Kurtz J, Sykes M, Rothstein DM, Tremblay JP.  Central tolerance to myogenic cell transplants does not include muscle neoantigens.  Transplantation. 2008 Jun 27;85(12):1791-801.
  • Fehr T, Wang S, Haspot F, Kurtz J, Blaha P, Hogan T, Chittenden M, Wekerle T, Sykes M.  Rapid deletional peripheral CD8 T cell tolerance induced by allogeneic bone marrow: role of donor class II MHC and B cells.  J Immunol. 2008 Sep 15;181(6):4371-80.
  • Kurtz J, Raval F, Vallot C, Der J, Sykes M. CTLA-4 on alloreactive CD4 T cells interacts with recipient CD80/86 to promote tolerance. Blood. 2009 Apr 9;113(15):3475-84. Epub 2009 Jan 29.
  • Mollov J, Lucas C, Haspot F, Kurtz J, Gaspar C, Guzman A, Sykes M. Recipient dendritic cells, but not B cells, are required antigen-presenting cells for peripheral alloreactive CD8+ T cell tolerance. Am J Transplant. 2010 Feb 1; 10(3): 518-526.
  • Fehr T, Lucas C, Kurtz J, Onoe T, Zhao G, Hogan T, Vallot C, Rao A, Sykes M.  A CD8 T cell-intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo. Blood 2010.  Feb 11;115(6):1280-7.  Epub 2009 Dec 10.
  • De Rio ML, Kurtz J, Perez-Martinez C, Ghosh A, Perez-Simon JA, Rodriguez-Barbosa JI.  B- and T-lymphocyte attenuator targeting protects against the acute phase of graft versus host reaction by inhibiting donor anti-host cytotoxicity.  Transplantation.  2011 Nov 27;92(10): 1085-93.

Reviews, Chapters, and Editorials:

  • T. Wekerle, J. Kurtz, and Megan Sykes.  Mixed hematopoietic chimerism and transplantation tolerance:  insights from experimental models.  Curr. Opin. Organ Transplant.  4:  44-49 (1999).
  • J. Kurtz and Megan Sykes.  Chapter 8:  Tolerance:  A review of its mechanisms in the transplant setting.  Pediatric Transplantation, edited by A. Tejani et al.  2000.
  • T. Wekerle, J. Kurtz, and M. Sykes.  Chapter 7:  Strategies for the Induction of Allograft Tolerance.  Cardiac Allograft Rejection, edited G. William Dec et al.  2001.
  • Wekerle T, Kurtz J, Bigenzahn S, Takeuchi Y, Sykes M. Mechanisms of transplant tolerance induction using costimulatory blockade.  Curr Opin Immunol. 2002 Oct;14(5):592-600.
  • Kurtz J, Wekerle T, Sykes M.  Tolerance in mixed chimerism - a role for regulatory cells?  Trends Immunol. 2004 Oct;25(10):518-23.
  • LoCascio S, Spinelli J, Kurtz J.  Hematopoietic Stem Cell Transplantation as Treatment of Autoimmunity in Type 1 Diabetes.  Curr Stem Cell Res Ther. 2011 Mar 1;6(1):29-37.
  • Leonard DA, McGrouther DA, Kurtz JM, Cetrulo Cl Jr.  Tolerance induction strategies in vascularized composite allotransplantation: mixed chimerism and novel developments.  Clin Dev Immunol.  Epub 2012 Dec 24.

NIRP: 
Immune function within the central nervous system (CNS) plays an important role regulating the health of the cellular constituents, and CNS immune dysfunction is implicated in many neurodegenerative and inflammatory diseases, such as Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Alzheimer's and Parkinson's. However, given their importance, the origin, recruitment, and effector mechanisms of those cells that regulate overall CNS immune function remain enigmatic. This project investigates the contribution and function of hematopoietically-derived progenitors to the central nervous system (CNS) population of microglia, the resident immune cells of the brain & spinal cord. We use a mouse hematopoietic chimerism model that utilizes green fluorescent protein expressing transgenic mice on the B6 background into wild type B6 recipients (GFPàB6; syngeneic) that allows for the identification and isolation of hematopoietically-derived macrophages within the CNS following bone marrow transplantation. Utilizing quantitative flow cytometry and qualitative histology/microscopy techniques, we investigate the molecular and cellular phenotypes (including pro-inflammatory markers and neurotransmitter receptor expression) of these cells compared to resident microglia. These detailed molecular, cellular, and anatomical characterizations and functional investigations will provide a strong foundation for future studies. 

TBRC/MGH:
Hand or face transplantation offers patients with upper-extremity or craniofacial tissue loss unparalleled restoration of function and form. Unfortunately, the highly immunogenic nature of skin (regarded as one of the most robust tests of immune tolerance) requires these patients to remain on substantial immunosuppressive regimens to prevent rejection of these vascularized composite allografts (VCAs).  Recently, we have developed a clinically-applicable protocol in a large animal model that allows for the indefinite survival of VCAs across a full MHC haplotype mismatch when transplanted concomitantly with hematopoietic stem cells from the VCA donor. In contrast to previous models, all components of the VCA skin (both dermis and epidermis) are accepted by the recipients with no evidence of either acute or chronic rejection, providing a unique model from which to elucidate the mechanisms involved in the establishment and maintenance of skin-specific tolerance through the establishment of mixed hematopoietic chimerism. Recent advances in the field of skin immunology have dramatically altered our understanding of the complexity and tissue-specific cell populations and processes required to balance the protective immune functions of the skin with remaining tolerance to all skin-specific self antigens. Using molecular and cellular techniques recently developed here at the Transplantation Biology Research Center at the Massachusetts General Hospital (by Emmanuel College graduates!), and the advantages of the inbred miniature swine model which allows for specific and reproducible MHC and minor antigen mismatching, these studies address the need for deeper understanding of the roles that genetics, central and peripheral mechanisms of tolerance, and the skin-specific cell populations all contribute in the establishment of tolerance of both dermal and epidermal components of the VCA.