Qizhi Tang, PhD
Description of Research
Treg cell therapy in autoimmune diseases and transplantation
Regulatory T cells (Tregs) are a small population of lymphocytes that suppresses the activity of other immune cells. They maintain normal immune homeostasis and safeguard against autoimmune diseases. Their immunosuppressive properties can also be harnessed to treat autoimmune diseases and to prevent transplant rejection. Research in my laboratory is focused on understanding the action of Tregs in vivo in mouse models of spontaneous type 1 diabetes and solid organ transplant rejection with the goal of developing novel Treg-based cellular therapies for autoimmunity and transplant rejection. Several current projects are to develop chimeric antigen receptor (CAR) and T cell receptor (TCR)-based approaches to redirect the specificity of Tregs to treat organ-specific autoimmune diseases and transplant rejection. We are optimizing CAR and TCR design to ensure the potency and lineage stability of Tregs. In the meantime, Tang lab members support the clinical Treg cell therapy program at UCSF (), which is currently conducting 6 clinical trials of Treg cell therapy in type 1 diabetes, islet transplantation, kidney transplantation and liver transplantation.
Effective and renewable beta cell replacement therapy for diabetes
Islet transplantation is an effective treatment of insulin-dependent diabetes, but is limited by low long-term efficacy and dependence on tissue from deceased donors. Furthermore, majority of islets die within days after transplantation due to ischemia and approaches to prevent beta cell death during this period can greatly improve the efficacy of this therapy. The Tang lab is developing approaches to mitigate post-transplant ischemic injury to beta cells. We have identified nutrient deprivation as a major and often overlooked contributor to beta cell death and discovered amino acid supplementation as an effective approach to prevent nutrient deprivation induce beta cell death. In the past year, we have identified the protective property of parathyroid gland in transplant islets and are actively developing a clinical trial to determine the efficacy of this approach patients with diabetes.
On renewable sources of beta cells, The Tang lab has been collaborating with the Hebrok lab in developing functional and immunologically silent stem-cell-derived beta cells. In collaboration with labs of Tejal Desai ad Shuvo Roy, we are developing bioengineering solutions to enable engraftment and long-term survival of stem cell derived beta cells without systemic immunosuppression. We are also actively developing collaborations to explore genetically engineered pig islets as a source of beta cells.
Immune mechanistic studies of transplant recipients
The Tang lab uses a set of functional cellular assays to assess the alloimmune status of transplant recipients. We have applied these assays to lung, kidney, and liver transplantation to investigate cellular events associated with graft rejection and tolerance. Specific projects include alloimmune correlates of chronic lung transplant pathology (in collaboration with Dr. John Greenland), mechanisms of heightened rejection in HIV+ kidney and liver transplant patients (in collaboration with Dr. Peter Stock), impact of novel immunosuppressive drugs on alloimmune response to kidney transplants (in collaboration with Dr. Flavio Vincenti), and alloimmune profiling of liver transplant patients in the context of Treg cell therapy and immunosuppression withdrawal (in collaboration with Dr. Sandy Feng).