Yiming Huang, M.D.

Yiming Huang, M.D.


Yiming Huang, M.D
Assistant Professor (Term)
y0huan01@louisville.edu
Tongji Medical University, 1985

Hematopoietic stem/progenitor cell (HSPC) transplantation has become a common procedure for the treatment of hematologic malignancies and autoimmune diseases.  Despite significant advances in clinical HSPC transplantation, the morbidity and mortality resulting from ablative conditioning and graft-versus-host disease (GVHD) continue to be obstacles.  However, these risks can be overcome through less toxic nonmyeloablative conditioning and cell depletion strategies that remove GVHD-causing cells while retaining engraftment-enhancing, tolerogenic cells. CD8+/TCR- facilitating cells in mouse bone marrow have been shown to enhance engraftment of HSPC in syngeneic and allogeneic mouse recipients.  Our recent studies showed that human FC from G-CSF mobilized PBMC enhance engraftment of human HSPC in NOD/SCID/IL2rγnull (NSG) mice.   The goal of our projects is to investigate the mechanisms of facilitating cells (FC) action on enhancing engraftment of HSPC avoiding GVHD and induction of transplantation tolerance.  Studies underway include (1) the mechanism of FC enhanced migration and homing of HSPC to bone marrow,  (2) the mechanism through which FC prevent apoptosis of HSPC,  (3) the role of FC on prevention of GVHD in an NSG model,  and (4) the function of FC induced antigen-specific regulatory T cells.

 

  1.  Huang, Y, Elliott, M.J., Yolcu, E.S., Miller, T., Ratajczak, J., Bozulic, L.D., Wen, Y., Xu, H., Ratajczak, M.Z., and Ildstad, S.T.: Characterization of human CD8+/TCR- facilitating cells in vitro and in vivo in a NOD/SCID/IL2rgnull mouse model. American Journal of Transplantation, 16:440, 2016.
  2. Wen, Y., Elliott, M.J., Huang, Y., Corbin, D.R., Miller, T.O., Hussain, L.R., Ratajczak, Y.F., Ildstad, S.T.: Critical role for DOCK2 in CD8+/TCR- graft facilitating cells enhancing engraftment of hematopoietic stem cells and inducing generation of regulatory T cells. Stem Cells, 32:2732, 2014.
  3. Leventhal, J., Huang, Y., Xu, H., Goode, I., and Ildstad, S.T.: Novel regulatory therapies for treatment and prevention of GVHD. BMC Medicine, 10:48, 2012.
  4. Bozulic, L.D., Huang, Y., Xu, H., Wen, Y., and Ildstad, S.T.: Differential outcomes in pre-diabetic vs. overtly diabetic NOD mice nonmyeloablatively conditioned with co-stimulatory blockade. Experimental Hematology, 39:977-985, 2011.
  5. Huang, Y., Bozulic, L.D., Miller, T., Xu, H., Hussain, L.R., and Ildstad, S.T.: CD8a+ plasmacytoid precursor dendritic cells induce antigen-specific regulatory T cell that enhance HSC engraftment. Blood, 117:2494-2505, 2011.
  6. Huang, Y., Enzmann, V., Ildstad, S.T.: Stem cell-based therapeutic application in retinal degenerative diseases. Stem Cell Rev. 7:434-445. 2011.
  7. Huang, Y., and Ildstad, S.T.: A novel role of innate immune responses (toll-like receptor-4) in triggering graft-versus-host disease. Transplantation, 90:1052-1053, 2010.
  8. Xu, H., Huang, Y., Hussain, L.R., Zhu, Z., Bozulic, L.D., Ding, C., Yan, J., and Ildstad, S.T.: Sensitization to minor antigens is a significant barrier in bone marrow transplantation and is prevented by CD154:CD40 blockade. Am J Transplant, 10:1569-1579, 2010.
  9. Huang, Y., Kucia, M., Hussain, L.R., Wen, Y., Xu, H., Yan, J., Ratajczak, M.Z., and Ildstad, S.T.:  Bone marrow transplantation temporarily improves pancreatic function in streptozotocin-induced diabetes: potential involvement of VSEL cells. Transplantation, 89:677-685, 2010.
  10. Huang, Y., Fugier-Vivier, I.J., Miller, T., Elliott, M.J., Tanner, M.K., Xu, H., Hussain, L.R., Bozulic, L.D., Chilton, P.M., and Ildstad, S.T.: Plasmacytoid precursor dendritic cells from NOD mice exhibit impaired function: are they a component of diabetes pathogenesis? Diabetes, 57:2360-2370, 2008.
  11. Xu, H., Huang, Y., Chilton, P.M., Hussain, L.R., Tanner, M.K., Yan, J., and Ildstad, S.T.: Strategic nonmyeloablative conditioning: CD154:CD40 co-stimulatory blockade at primary BMT promotes engraftment for secondary BMT after engraftment failure. J. Immunol, 181:6616-6624, 2008.
  12. Huang, Y., Ratajczak, M.Z., Reca, R., Xu, H., Tanner, M., Rezzoug, F., Hussain, L-R, Fugier-Vivier, I., Bolli, R., and Ildstad, S.T.: Flt3 expression discriminates HSC subpopulations with differing engraftment-potential: identifying the most potent combination. Transplantation, 85:1175-1184, 2008.
  13. Rezzoug, F., Huang, Y., Tanner, M., Wysoczynski, M., Schanie, C.L., Chilton, P.M., Ratajczak, M.Z., Fugier-Vivier, I., and Ildstad, S.T.: TNFa is critical to facilitate hematopoietic stem cell engraftment and function.  Journal of Immunology, 180:49-57, 2008.
  14. Xu, H., Yan, J., Huang, Y., Chilton, P.M., Ding, C., Schanie, C.L., Wang, L., and Ildstad, S.T.: Co-stimulatory blockade of CD154:CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization. Blood, 111:3266-3275, 2008.
  15. Xu, H., Chilton, P.M., Tanner, M.K, Huang, Y.,Schanie, C.L., Dy-Liacco, M., Yan, J., and Ildstad, S.T.:  Humoral Immunity is the Dominant Barrier for Allogeneic Bone Marrow Engraftment in Sensitized Recipients. Blood 108:3611-3619, 2006.
  16. Dawn, B., Guo, Y., Rezazadeh, A., Huang, Y., Stein, A.B., Hunt, G., Tiwari, S., Prabhu, S.D., Gu, Y., Varma, J., Kajstura, J., Anversa, P., Ildstad, S.T., Bolli, R.:  Postinfarct cytokine therapy regenerates cardiac tissue and improves left ventricular function. Circulation Research 98:1098-1105, 2006.
  17. Huang, Y., Kucia, M., Rezzoug, F., Ratajczak, J., Tanner, M.K.,Ratajczak, M.Z., Schanie, C.L., Xu, H., and Ildstad, S.T.:  FL-mobilized peripheral blood but not FL-expanded bone marrow FC promote establishment of chimerism and tolerance.  Stem Cells 24:936-948, 2006.
  18. Huang, Y., Rezzoug, F., Xu, H., Chilton, P.M., Schanie, C., Fugier, I., and Ildstad, S.T.: Natural killer cells play a critical role on regulation of Class I deficient hematopoietic stem cells engraftment: evidence for NK tolerance correlates with receptor editing. Journal of Immunology 175:3753-3761, 2005.
  19. Chilton, P.M., Rezzoug, F., Ratajczak, M.Z., Vivier-Fugier, I., Ratajczak, J., Kucia, M., Huang, Y., Tanner, M.K., and Ildstad, S.T.: Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients. Blood 105:2189-2197, 2005.
  20. Fugier, I., Rezzoug, F., Huang, Y., Graul-Layman, A.J.,Schanie, C.L., Xu, H., Chilton, P.M., and Ildstad, S.T.: Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cells engraftment. Journal of Experimental Medicine 201:373-383, 2005.
  21. Colson, Y.L., Xu, H., Huang, Y., and Ildstad, S.T.: Mixed xenogeneic chimerism induces donor-specific humoral and cellular immune tolerance for cardiac xenografts. Journal of Immunology 173:5827-5834, 2004.
  22. Grimes, H.L., Schanie, C., Huang, Y., Fugier, I., Cramer, D., Rezzoug, F., and Ildstad, S.T.: Graft facilitating cells: evidence for a distinct non-T cell lymphoid lineage. Experimental hematology 32:946-954, 2004.
  23. Chilton, P.M., Rezzoug, F., Fugier-ViVier, I., Weeter, L.A., Xu, H., Huang, Y., Ray, M.B., and Ildstad, S.T.: Flt3 ligand treatment prevents diabetes in NOD mice.  Diabetes 53:1995-2002, 2004.
  24. Huang, Y., Rezzoug, F., Chilton, P.M., Grimes, H.L., Cramer, D.E., and Ildstad, S.T.: MHC at the MHC Class I K locus is essential for long-term engraftment of purified hematopoietic stem cells: a role for host NK cells in regulating HSC engraftment. Blood 104:873-880, 2004.
  25. Xu, H., Chilton, P.M., Huang, Y., Schanie, C.L., and Ildstad, S.T.: Production of donor T cells is critical for induction of donor-specific tolerance and maintenance of chimerism. Journal of Immunology 172:1463-1471, 2004.
  26. Huang, Y., Cramer, D.E., Ray, M.B., Chilton, P.M., Que, X., and Ildstad, S.T.: The role of ab and gd TCR+ T cell in allogeneic donor marrow on chimerism, engraftment and graft-versus-host disease. Transplantation 72:1907-1914, 2001.
  27. Huang, Y., Ildstad, S.T., Neipp, M., and Shirwan. H.: Mouse xenoantigens contribute to rat T-cell Vb repertoire generation in mixed Xenogeneic bone marrow chimeras. Immunology 100:317-325, 2000.