Leslie S. Kean, MD, PhD - Basic Science Research Faculty

Leslie S. Kean, MD, PhD

Fellow and McKelvey Scholar
Department of Pediatrics
Division of Hematology/Oncology/Bone Marrow Transplantation
Emory University School of Medicine, Emory Transplant Center

Transplantation tolerance, defined as long-term mutual immunologic acceptance between transplant donor and recipient, in the absence of immunosuppression, remains an elusive goal of clinical transplantation. Dr. Kean's work at the ETC has been at the center of research that has focused on understanding mechanisms leading to transplantation tolerance, with the ultimate goal of translating knowledge of these mechanisms to clinical transplantation. Over the past several years, our group and others have developed strategies targeting the CD40 and CD28 T cell costimulation pathways to control allograft rejection in murine models. By providing costimulation blockade in the peri-transplant period, existing donor-reactive T cells receive “signal one” (supplied by donor cells and antigens) in the absence of “signal two” and are preferentially deleted. This leads to robust, long-term tolerance when normal mice are transplanted under the protection of costimulation blockade. However, when more immunologically complex systems are transplanted with these same techniques, true immunologic tolerance is more difficult to achieve.

Dr. Kean's work is focused on four specific questions, all related to transplantation tolerance, and its acquisition in immunologically complex model systems:

  1. In a highly immunologically active model of a non-malignant hematologic disease (sickle cell disease) what are the major barriers to the acquisition of transplantation tolerance?  
  2. How do natural killer cells impact the acquisition of transplantation tolerance, and can control of natural-killer alloreactivity produce transplantation tolerance in otherwise resistant models?  
  3. In the non-human primate model, what are the major barriers to the acquisition of transplantation tolerance, and can we combine blockade of the costimulation pathway with adoptive cellular therapies to achieve robust donor specific tolerance?  
  4. During bone marrow transplantation in a rhesus macaque model, what are the barriers to tolerance that result in graft-versus host disease, and can these underlying immune barriers be overcome by costimulation-blockade based immunomodulation strategy?

Dr. Kean received her MD/PhD at Emory University in 1999 and completed post-doctoral research, residency and fellowship in Pediatrics and Pediatric Hematology/Oncology in 2005 at Emory University Hospitals and the Aflac Cancer Center and Blood Disorders Service at Children’s Healthcare of Atlanta. On Faculty since 2005, Dr. Kean currently holds a Burroughs Wellcome Career Award in the Biomedical Sciences, A K08 Clinician Scientist Award from the NIH, and is the Principal Investigator on one of two projects focused on primate transplantation tolerance funded by a NIH U19 Cooperative Group award. She also has funding through the Emory Children’s Center for her novel model of graft-versus-host disease in a non-human primate model, the first of its kind in the world.

Recent Publications (2007 – 2008)

  • Alan Anderson,Christine Martens, Rose Hendrix, Linda Stempora, Wes Miller, Kelly Hamby, Maria Russell, Elizabeth Strobert, Bruce R. Blazar, Thomas C. Pearson, Christian P. Larsen and Leslie S. Kean. 2008. Expanded Non-human Primate Tregs Exhibit A Unique Gene Expression Signature and Potently Downregulate Allo-immune Responses. Am J. Transplant In press.  
  • Stapler D., Lee ED, Slvaraj SA, Evans AG, Kean LS, Speck SH, Larsen CJP, GAngappa S. 2008 Expansion of Effector Memory TCR Vb4+CD8+ T Cells Is Associated with Latent Infection-Mediated Resistance to Transplantation Tolerance. J Immunol. Mar 1; 180(5):3190-3200.  
  • Linzie K, Trexler A, Pearson TC, Larsen CP, Rigby MR and Kean LS. 2007. NK cells rapidly reject allogeneic bone marrow in the spleen through a Perforin- and Ly49D-dependent, but NKG2D-independent mechanism. Am J. Transplant 7(8): 1884-1896.  
  • Zahorchak AF, Kean LS, Tokita D, Turnquist HR, Abe M, Finke J, Hamby K, Rigby MR, Larsen CP, Thomson AW. 2007. Infusion of Stably-Immature Monocyte-Derived Dendritic Cells Plus CTLA4-Ig Modulates Alloimmune Reactivity in Rhesus Macaques. Transplantation 84(2): 196-206.  
  • Kean LS, Adams AB, Strobert E, Hendrix R, Gangappa S, Jones TR, Shirasugi N, Rigby MR, Hamby K, Jiang J, Bello H, Anderson D, Cardona K, Durham MM, Pearson TC, and Larsen CP. 2007. Induction of Chimerism in Rhesus Macaques through Stem Cell Transplant and Costimulation Blockade-Based Immunosuppression. Am J. Transplant 7(2):320-35.