Yong-Guang Yang

Transplantation Biology Research Center
Department of Surgery
Massachusetts General Hospital
MGH-East, Building 149-5210, 13th Street
Boston, MA 02129

Phone: (617) 726-6959
Fax: (617) 726-5414
email: yongguang.yang@tbrc.mgh.harvard.edu
1 instructor, 3 postdoctoral fellows, 3 research scientists

Inhibitory receptor-ligand interactions in xenograft rejection: CD47 is a ligand of an inhibitory receptor, signal regulatory protein (SIRP)a, and its interaction with SIRPa on macrophages prevents phagocytosis of autologous hematopoietic cells. We have discovered that interspecies incompatibility of CD47 contributes significantly to phagocytosis of xenogeneic cells by macrophages. We also demonstrated that the phagocytic activity of macrophages against CD47-deficient cells is conferred by CD47 expression on nonhematopoietic cells, and that lack of CD47 on nonhematopoietic cells induces macrophage tolerance to CD47-deficient cells. Ongoing research is focused on defining the mechanisms of macrophage tolerance and developing novel strategies for controlling xenograft rejection by macrophages.

GVHD vs. GVL in allogeneic hematopoietic cell transplantation (allo-HCT): Graft-vs.-host disease (GVHD) remains the major complication of allo-HCT, the only curative therapy for many hematopoietic malignancies. We have shown that IFN-gamma plays an important role in controlling the alloresponses of donor T cells and determines whether they will predominantly mediate GVHD or graft-vs.-leukemia (GVL) effects. We are currently studying the molecular and cellular mechanisms by which IFN-gamma regulates the alloreactivity of donor T cells.

Humanized mouse models for the study of human immune function in vivo: We have established a humanized mouse (hu-mouse) model with a functional human immune system. These hu-mice show normal human thymopoiesis, systemic repopulation with multilineages of human lymphohematopoietic cells (e.g., T, B and dendritic cells), formation of secondary lymphoid organs with normal architecture, and strong antigen-specific T cell and antibody responses upon immunization. We are currently using hu-mice as an in vivo model system for elucidating human immune responses in allogeneic and xenogeneic transplantation settings.

Papers & Publications:

Wang H, Madariaga ML, Wang S, Oldenborg P-A, Yang YG. Lack of CD47 on non-hematopoietic cells induces split macrophage tolerance to CD47null Cells. Proc Natl Acad Sci USA 2007;104:13744-13749.

Wang H, VerHalen J, Madariaga ML, Xiang S, Wang S, Lan P, Oldenborg P-A, Sykes M, Yang YG. Attenuation of phagocytosis of xenogeneic cells by manipulating CD47. Blood 2007;109:836-842.

Ide K, Wang H, Liu J, Wang X, Asahara T, Sykes M, Yang YG, Ohdan H. Role for CD47-SIRPa signaling in xenograft rejection by macrophages. Proc Natl Acad Sci USA 2007;104:5062-6.

Yang YG, Sykes M. Xenotransplantation - Current Status and a Perspective on the Future. Nature Reviews Immunology 2007;7:519-531.

Tonomura N, Habiro K, Shimizu A, Sykes M, Yang YG. Antigen specific human T cell responses and T cell-dependent production of human antibodies in a humanized mouse model. Blood 2008 111:4293-4296.