Research

Dai, Zhenhua, M.D., Ph.D.

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Contact: zhenhua.dai@uthct.edu

Education:
M.D. Jiangxi Medical College, 1988, China
Ph.D. Beijing Medical University, 1996, Beijing, China

Research Interest:
Adaptive immunity that mediates transplantation rejection, the mechanisms of T cell activation/regulation and strategies to induce transplantation tolerance or long-term graft survival by manipulating immune system.

Current Projects:

  1. Induction of pancreatic islet transplantation tolerance or long-term graft survival by taking advantage of immune privileged sites such as the testis and eye.
  2. Investigation into the cellular and molecular mechanisms of immune privilege that promote engraftment or tolerance.
  3. Evaluation of the role for regulatory T cells in transplantation tolerance or long-term graft survival and its mechanisms.
  4. Identification of target molecules and cells such as OX40, 4-1BB and memory T cells to foster transplantation tolerance or long-term graft survival.

Lay Summary:
Transplanted recipients always reject grafts unless they take immunosuppressive agents for the rest of their lives. Immunosuppressive treatments may cause serious side-effects such as viral infection and tumor. Transplantation tolerance, defined as indefinite transplanted organ/tissue survival and function without immunosuppressive treatments, is a highly desired goal in the field of transplantation.

Immunological T cells are major forces that protect individuals against foreign invasion such as bacteria and viruses. Unfortunately T cells also respond to donor organs such as islets and cause rapid graft rejection. To induce transplantation tolerance, T cell function must be modified. Current approaches including costimulation blockade and immunosuppression fail to consistently induce tolerance in normal animals. There are certain areas in a body such as the testis where T cell function is naturally suppressed. These sites, called immune privileged sites, may create a unique opportunity to induce tolerance. We have recently found that a single costimulation-blockade induces islet allograft tolerance in the testis, an immune privileged site, but not in a conventional site such as the kidney. We therefore propose to study the mechanisms underlying transplantation tolerance mediated by testicular immune privilege. We will largely focus our studies on regulatory T cells, good ones that suppress graft rejection, and memory T cells, bad ones or hard-liners that reject grafts. This proposal may reveal novel strategies to induce transplantation tolerance and thus provide a cure for end-stage organ diseases via transplantation.

Research Overview:
Induction of pancreatic islet transplantation tolerance or long-term graft survival by taking advantage of immune privileged sites such as the testis and eye.

Investigation into the cellular and molecular mechanisms of immune privilege that promote engraftment or allograft tolerance.

Evaluation of the role for regulatory T cells in transplantation tolerance or long-term graft survival and the biology of regulatory T cells such as their homeostasis, activation and apoptosis.

Dissecting the role for memory T cells in treatment-resistant allograft rejection and the biology of memory T cells such as their generation, maintenance and apoptosis.

Identification of target costimulatory molecules such as OX40, 4-1BB, and CD30 etc to foster transplantation tolerance or long-term graft survival.

Selected Papers and Abstracts: