Biography
The Tang lab focuses on translating knowledge on mechanisms of immune tolerance into novel therapeutics for treating autoimmune diabetes and preventing transplant rejection. Currently, two major areas of work are on therapeutic application of regulatory T cell therapy in type 1 diabetes and transplantation and immune modulation to enable immune suppression-free transplant of stem-cell-derived beta cells for treatment of type 1 diabetes.
Regulatory T cells are a small population of white blood cells that are essential for preventing tissue damages caused by over activation of the immune system. The Tang lab has shown that infusion of regulatory T cells in animal models can reverse type 1 diabetes, a disease caused by immune destruction of insulin-producing cells in the pancreatic islets. Similarly, regulatory T cell therapy can prevent rejection of transplanted organs in animal models. A joint team of researchers from the Tang and Bluestone labs is currently conducting 6 clinical trials evaluating the safety and efficacy of regulatory T cell therapy in patients. In the mean time, we are developing next generation regulatory T cell therapies in preclinical models to improve the safety and efficacy of the therapy.
In patients with chronic type 1 diabetes, transplanting of stem-cell-derived beta cells can potentially cure the disease, but patients have to commit to life-long immunosuppression to prevent rejection of the transplanted cells from rejection by the immune system. The Tang lab is currently investigating approaches to shield the transplanted cells from the immune systems using novel biomaterials developed in the Desai and Roy labs at UCSF. We are also applying genome-editing technologies to immunoengineer stem cells to evade immune rejection.
Regulatory T cells are a small population of white blood cells that are essential for preventing tissue damages caused by over activation of the immune system. The Tang lab has shown that infusion of regulatory T cells in animal models can reverse type 1 diabetes, a disease caused by immune destruction of insulin-producing cells in the pancreatic islets. Similarly, regulatory T cell therapy can prevent rejection of transplanted organs in animal models. A joint team of researchers from the Tang and Bluestone labs is currently conducting 6 clinical trials evaluating the safety and efficacy of regulatory T cell therapy in patients. In the mean time, we are developing next generation regulatory T cell therapies in preclinical models to improve the safety and efficacy of the therapy.
In patients with chronic type 1 diabetes, transplanting of stem-cell-derived beta cells can potentially cure the disease, but patients have to commit to life-long immunosuppression to prevent rejection of the transplanted cells from rejection by the immune system. The Tang lab is currently investigating approaches to shield the transplanted cells from the immune systems using novel biomaterials developed in the Desai and Roy labs at UCSF. We are also applying genome-editing technologies to immunoengineer stem cells to evade immune rejection.
Education
Institution | Degree | Dept or School | End Date |
---|---|---|---|
University of California | Diversity, Equity, and Inclusion Champion Training | 2021 | |
University of California | Postdoctoral Studies | Immunology | 2002 |
Univeristy of Chicago | Postdoctoral Studies | Immunology | 2000 |
University of Illinios | PhD | Microbiology and Immunology | 1996 |
University of South Alabama | Graduate School | Microbiology and Immunology | 1991 |
Peking Union Medical College | Medical School | Medcine | 1989 |
Clinical Trials
- Related Conditions: Liver Transplant| Start Date: | End Date:
Grants and Funding
- Pancreatic Islets and Parathyroid Gland Co-transplantation for Treatment of Diabetes in the Intra-Muscular Site: PARADIGM | CIRM | 2019-07-01 - 2023-06-30 | Role: Co-investigator
- Islet transplant operational tolerance through minimization of ischemic injury and local immune regulation | JDRF | 2019-09-01 - 2021-08-31 | Role: PI
- Novel Therapies to Modulate the Inflammatory Alloresponse in Renal Grafts | NIAID | 2014-07-01 - 2021-06-30 | Role: Co-investigator
- Multiplex in situ gene expression and phenotypical profiling of inflamed tissues | NIH | 2015-06-26 - 2021-05-31 | Role: Co-Principal Investigator
- Donor-Alloantigen-Reactive Regulatory T Cell Therapy in Liver Transplantation | NIH | 2014-06-01 - 2021-05-31 | Role: Co-Principal Investigator
- Diabetes Research Center | NIH | 2002-09-01 - 2021-03-31 | Role: Co-Investigator
- Engineering Treg cells to treat type 1 diabetes | Helmsley Charitable Trust | 2017-11-01 - 2020-10-31 | Role: PI
- Promoting extrahepatic engraftment of human islets by parathyroid gland co-transplantation | JDRF | 2018-06-01 - 2019-05-31 | Role: PI
- Regulatory 'T' Cell Control of Autoimmune Diabetes. | NIH | 2010-03-15 - 2016-02-29 | Role: Principal Investigator
- Donor-Specific Regulatory T Cell Therapy in Liver Transplantation | NIH | 2012-04-01 - 2014-03-31 | Role: Co-Principal Investigator
- BD FACS ARIA II CELL SORTER | NIH | 2010-02-01 - 2011-01-31 | Role: Principal Investigator
- Visualizing regulatory T cell control of autoimmunity | NIH | 2005-07-01 - 2008-06-30 | Role: Principal Investigator
- T CELL ACTIVATION AND ANERGY INDUCTION BY ANTI-CD3 | NIH | 2000-02-01 - 1900-01-01 | Role: Principal Investigator
Research Interests
T-Lymphocyte Subsets
T-Lymphocytes
Suppressor-Effector
Autoimmunity
Islets of Langerhans Transplantation
Transplantation Immunology
Transplantation Tolerance
Immune Tolerance
Immunotherapy
Research Pathways
Publications
MOST RECENT PUBLICATIONS FROM A TOTAL OF 122
- Harnessing regulatory T cells to establish immune tolerance.| | PubMed
- Precise surface functionalization of PLGA particles for human T cell modulation.| | PubMed
- Epidermal Stem Cell Derived Exosomes Alleviate Excessive Autophagy Induced Endothelial Cell Apoptosis by Delivering miR200b-3p to Diabetic Wounds.| | PubMed
- Feasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes.| | PubMed
- Regulatory T cells targeting a pathogenic MHC class II: Insulin peptide epitope postpone spontaneous autoimmune diabetes.| | PubMed
- Donor antigen-specific regulatory T cell administration to recipients of live donor kidneys: A ONE Study consortium pilot trial.| | PubMed
- Regulatory T cells aid stem-cell therapy for Parkinson's disease.| | PubMed
- Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous space.| | PubMed
- Impact of interleukin-6 on T cells in kidney transplant recipients.| | PubMed
- The dichotomous outcomes of TNFα signaling in CD4+ T cells.| | PubMed
- Selective decrease of donor-reactive Tregs after liver transplantation limits Treg therapy for promoting allograft tolerance in humans.| | PubMed
- A Phase I/IIa study of autologous tolerogenic dendritic cells immunotherapy in kidney transplant recipients.| | PubMed
- Anti-HLA-A2-CAR Tregs prolong vascularized mouse heterotopic heart allograft survival.| | PubMed
- IL-6 and TNFα Drive Extensive Proliferation of Human Tregs Without Compromising Their Lineage Stability or Function.| | PubMed
- Lung transplant recipients with idiopathic pulmonary fibrosis have impaired alloreactive immune responses.| | PubMed
- Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience.| | PubMed
- The effect of low-dose IL-2 and Treg adoptive cell therapy in patients with type 1 diabetes.| | PubMed
- Precision Engineering of an Anti-HLA-A2 Chimeric Antigen Receptor in Regulatory T Cells for Transplant Immune Tolerance.| | PubMed
- The Role of Regulatory T Cells in Pulmonary Arterial Hypertension.| | PubMed
- Selective deletion of human leukocyte antigens protects stem cell-derived islets from immune rejection.| | PubMed
- A Comparison of Ex Vivo Expanded Human Regulatory T Cells Using Allogeneic Stimulated B Cells or Monocyte-Derived Dendritic Cells.| | PubMed
- A human mutation in STAT3 promotes type 1 diabetes through a defect in CD8+ T cell tolerance.| | PubMed
- The CD28-Transmembrane Domain Mediates Chimeric Antigen Receptor Heterodimerization With CD28.| | PubMed
- Interleukin-6 blockade with tocilizumab increases Tregs and reduces T effector cytokines in renal graft inflammation: A randomized controlled trial.| | PubMed
- Solving the Puzzle of Immune Tolerance for β-Cell Replacement Therapy for Type 1 Diabetes.| | PubMed
- Functional CRISPR dissection of gene networks controlling human regulatory T cell identity.| | PubMed
- CAR-Tregs as a Strategy for Inducing Graft Tolerance.| | PubMed
- Novel In Situ Hybridization and Multiplex Immunofluorescence Technology Combined With Whole-slide Digital Image Analysis in Kidney Transplantation.| | PubMed
- Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials.| | PubMed
- Next-generation regulatory T cell therapy.| | PubMed
- Supporting Survival of Transplanted Stem-Cell-Derived Insulin-Producing Cells in an Encapsulation Device Augmented with Controlled Release of Amino Acids.| | PubMed
- NextGen cell-based immunotherapies in cancer and other immune disorders.| | PubMed
- NKG2C Natural Killer Cells in Bronchoalveolar Lavage Are Associated With Cytomegalovirus Viremia and Poor Outcomes in Lung Allograft Recipients.| | PubMed
- Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus.| | PubMed
- Early expansion of donor-specific Tregs in tolerant kidney transplant recipients.| | PubMed
- Islet encapsulation therapy - racing towards the finish line?| | PubMed
- Regulatory T-cell therapy for autoimmune and autoinflammatory diseases: The next frontier.| | PubMed
- Treg cells-the next frontier of cell therapy.| | PubMed
- Report of the Key Opinion Leaders Meeting on Stem Cell-derived Beta Cells.| | PubMed
- Stem Cell Therapies for Treating Diabetes: Progress and Remaining Challenges.| | PubMed
- Suppressed calcineurin-dependent gene expression identifies lung allograft recipients at increased risk of infection.| | PubMed
- Revealing the specificity of regulatory T cells in murine autoimmune diabetes.| | PubMed
- Alloreactive fetal T cells promote uterine contractility in preterm labor via IFN-γ and TNF-α.| | PubMed
- Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization.| | PubMed
- Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant.| | PubMed
- Nanoporous Immunoprotective Device for Stem-Cell-Derived β-Cell Replacement Therapy.| | PubMed
- Transplant trials with Tregs: perils and promises.| | PubMed
- Cutting Edge: Origins, Recruitment, and Regulation of CD11c+ Cells in Inflamed Islets of Autoimmune Diabetes Mice.| | PubMed
- Glucose-Stimulated Insulin Response of Silicon Nanopore-Immunoprotected Islets under Convective Transport.| | PubMed
- Islet-Derived CD4 T Cells Targeting Proinsulin in Human Autoimmune Diabetes.| | PubMed
- Impact of Immune-Modulatory Drugs on Regulatory T Cell.| | PubMed
- Restoring Regulatory T Cells in Type 1 Diabetes.| | PubMed
- Donor-Reactive Regulatory T Cell Frequency Increases During Acute Cellular Rejection of Lung Allografts.| | PubMed
- Virtual Global Transplant Laboratory Standard Operating Procedures for Blood Collection, PBMC Isolation, and Storage.| | PubMed
- Assessment of Immune Isolation of Allogeneic Mouse Pancreatic Progenitor Cells by a Macroencapsulation Device.| | PubMed
- Heightened Immune Activation in Fetuses with Gastroschisis May Be Blocked by Targeting IL-5.| | PubMed
- Silicon nanopore membrane (SNM) for islet encapsulation and immunoisolation under convective transport.| | PubMed
- Approaching a cure for type 1 diabetes.| | PubMed
- Manipulating IL-2 and IL-2R in autoimmune diseases and transplantation.| | PubMed
- Type 1 diabetes immunotherapy using polyclonal regulatory T cells.| | PubMed
- Targeting Treg signaling for the treatment of autoimmune diseases.| | PubMed
- Therapeutic window of interleukin-2 for autoimmune diseases.| | PubMed
- Polycaprolactone Thin-Film Micro- and Nanoporous Cell-Encapsulation Devices.| | PubMed
- Immunotherapy: making the case for precision medicine.| | PubMed
- Increased maternal T cell microchimerism in the allogeneic fetus during LPS-induced preterm labor in mice.| | PubMed
- Therapeutic regulatory T cells subvert effector T cell function in inflamed islets to halt autoimmune diabetes.| | PubMed
- Antigen recognition in the islets changes with progression of autoimmune islet infiltration.| | PubMed
- Interpretation of transplant biopsies and immune responses following Treg cell therapy.| | PubMed
- Fetal intervention increases maternal T cell awareness of the foreign conceptus and can lead to immune-mediated fetal demise.| | PubMed
- Regulatory T-cell therapy in transplantation: moving to the clinic.| | PubMed
- Direct and indirect antigen presentation lead to deletion of donor-specific T cells after in utero hematopoietic cell transplantation in mice.| | PubMed
- Altered balance between effector T cells and FOXP3+ HELIOS+ regulatory T cells after thymoglobulin induction in kidney transplant recipients.| | PubMed
- IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress.| | PubMed
- Regulatory T-cell therapy for transplantation: how many cells do we need?| | PubMed
- CD4(+)Foxp3(+) regulatory T cell therapy in transplantation.| | PubMed
- B cell-derived IL-10 suppresses inflammatory disease in Lyn-deficient mice.| | PubMed
- Anti-CD3 therapy promotes tolerance by selectively depleting pathogenic cells while preserving regulatory T cells.| | PubMed
- Requirements for prolongation of allograft survival with regulatory T cell infusion in lymphosufficient hosts.| | PubMed
- The maternal immune response inhibits the success of in utero hematopoietic cell transplantation.| | PubMed
- Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice.| | PubMed
- IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells.| | PubMed
- Prevention of diabetes by FTY720-mediated stabilization of peri-islet tertiary lymphoid organs.| | PubMed
- Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal.| | PubMed
- Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues.| | PubMed
- T regulatory cells in autoimmune diabetes: past challenges, future prospects.| | PubMed
- Spontaneous development of a pancreatic exocrine disease in CD28-deficient NOD mice.| | PubMed
- Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction.| | PubMed
- The Foxp3+ regulatory T cell: a jack of all trades, master of regulation.| | PubMed
- Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice.| | PubMed
- Exendin-4 improves reversal of diabetes in NOD mice treated with anti-CD3 monoclonal antibody by enhancing recovery of beta-cells.| | PubMed
- Mechanisms of PDL1-mediated regulation of autoimmune diabetes.| | PubMed
- Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway.| | PubMed
- Regulatory T-cell physiology and application to treat autoimmunity.| | PubMed
- Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo expanded regulatory T cells.| | PubMed
- Imaging the function of regulatory T cells in vivo.| | PubMed
- Plasmacytoid DCs and T(reg) cells: casual acquaintance or monogamous relationship?| | PubMed
- Antigen-specific regulatory T cells--ex vivo expansion and therapeutic potential.| | PubMed
- Ex vivo-expanded CD4+CD25+ immunoregulatory T cells prevent graft-versus-host-disease by inhibiting activation/differentiation of pathogenic T cells.| | PubMed
- Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice.| | PubMed
- How do CD4+CD25+ regulatory T cells control autoimmunity?| | PubMed
- Expansion of functional endogenous antigen-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice.| | PubMed
- Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T cell function.| | PubMed
- Therapeutic vaccination using CD4+CD25+ antigen-specific regulatory T cells.| | PubMed
- In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes.| | PubMed
- Notch 1 signaling regulates peripheral T cell activation.| | PubMed
- Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells.| | PubMed
- CD28/B7 regulation of anti-CD3-mediated immunosuppression in vivo.| | PubMed
- CTLA-4 regulates the requirement for cytokine-induced signals in T(H)2 lineage commitment.| | PubMed
- The role of CD28 and CTLA4 in the function and homeostasis of CD4+CD25+ regulatory T cells.| | PubMed
- The Src family kinase Fyn mediates signals induced by TCR antagonists.| | PubMed
- ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse.| | PubMed
- Antigen-specific blockade of T cells in vivo using dimeric MHC peptide.| | PubMed
- Development and applications of surface-linked single chain antibodies against T-cell antigens.| | PubMed
- Partial TCR signals delivered by FcR-nonbinding anti-CD3 monoclonal antibodies differentially regulate individual Th subsets.| | PubMed
- T cell receptor-gamma/delta cells protect mice from herpes simplex virus type 1-induced lethal encephalitis.| | PubMed
- Proinflammatory functions of IL-2 in herpes simplex virus corneal infection.| | PubMed
- Interferon gamma regulates platelet endothelial cell adhesion molecule 1 expression and neutrophil infiltration into herpes simplex virus-infected mouse corneas.| | PubMed
- Ex vivo model of leukocyte migration into herpes simplex virus-infected mouse corneas.| | PubMed
- Inflammatory infiltration of the trigeminal ganglion after herpes simplex virus type 1 corneal infection.| | PubMed
- Involvement of LFA-1 and ICAM-1 in the herpetic disease resulting from HSV-1 corneal infection.| | PubMed
- Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells.| | PubMed
- IL-8 gene expression in cultures of human corneal epithelial cells and keratocytes.| | PubMed