Yiping Yang

Overview:

The goal of Dr. Yang’s laboratory is to understand the molecular and cellular mechanisms leading to the generation of potent and long-lasting anti-tumor immunity, and to develop effective gene immunotherapeutic strategies for treating cancer. Furthermore, rational pre-clinical approaches will be tested in clinical trials in patients with Epstein-Barr virus (EBV)-related malignancies. Specifically, we focus on the following areas:

1. Innate Immunity to Viruses. Recombinant vaccinia virus and adenovirus have been developed as potent vaccine vehicles for treating cancer and infectious diseases. Recent studies have shown that the unique potency of these viruses lies in their effective activation of the innate immune system. How these viruses activate the innate immune system remains largely unknown. We have been interested in the role of pattern-recognition receptors including Toll-like receptors (TLRs)in innate immune recognition of these viruses as well as their signaling pathways. In addition, we are investigating the role of innate immune cells such as natural killer (NK) cells in innate and adaptive immune responses to these viruses. A full understanding of these processes will help us design effective vaccine strategies.

2. T Cell Memory. Eliciting long-lived memory T cell response is an ultimate goal of vaccination to provide long-term immunity against cancer. However, it is not clear what controls the formation of long-lived memory T cells. The understanding of mechanisms underlying memory T cell formation will provide important insights into the design of effective vaccines for treating cancer.

3. Regulatory T Cell Biology. Accumulating evidence has shown that the immunosuppressive CD4+CD25+Foxp3+ regulatory T cells (TReg) play a critical role in the suppression of anti-tumor immunity. However, little is known about how TReg suppress T cell activation in vivo. Delineation of mechanisms underlying TReg-mediated suppression in vivo will help develop strategies to overcome TReg-mediated suppression in favor of boosting anti-tumor immunity.

4. Immunotherapy for EBV-associated Malignancies. Clinically, EBV-associated malignancies such as Hodgkin’s lymphoma offer a unique model to explore antigen-defined immunotherapy approaches because EBV-derived tumor antigens are specific for tumor cells only. Using this clinical model, we will test the utility of rational strategies identified in our preclinical models.

Positions:

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Professor of Immunology

Immunology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1985

Zhejiang University (China)

Ph.D. 1993

University of Michigan at Ann Arbor

Residency, General Internal Medicine

University of Pennsylvania School of Medicine

Fellowship, Medical Oncology

Johns Hopkins University School of Medicine

Grants:

Role of hedgehog signaling in tumor-associated macrophage polarization

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

T memory stem cells in cancer

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Novel Strategies for Cancer Immunotherapy in Stem Cell Transplant

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Role of Endogenous Toll-Like Receptor Ligands in Allospecific T Cell Activation

Administered By
Surgery, Abdominal Transplant Surgery
Awarded By
National Institutes of Health
Role
Mentor
Start Date
End Date

Role of inflammation in cancer progression

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Chimeric Antigen Receptor T Cell Therapy for Solid Tumors: Current Status, Obstacles and Future Strategies.

Chimeric antigen receptor T cells (CAR T Cells) have led to dramatic improvements in the survival of cancer patients, most notably those with hematologic malignancies. Early phase clinical trials in patients with solid tumors have demonstrated them to be feasible, but unfortunately has yielded limited efficacy for various cancer types. In this article we will review the background on CAR T cells for the treatment of solid tumors, focusing on the unique obstacles that solid tumors present for the development of adoptive T cell therapy, and the novel approaches currently under development to overcome these hurdles.
Authors
Heyman, B; Yang, Y
MLA Citation
Heyman, Benjamin, and Yiping Yang. “Chimeric Antigen Receptor T Cell Therapy for Solid Tumors: Current Status, Obstacles and Future Strategies..” Cancers (Basel), vol. 11, no. 2, Feb. 2019. Pubmed, doi:10.3390/cancers11020191.
URI
https://scholars.duke.edu/individual/pub1369036
PMID
30736355
Source
pubmed
Published In
Cancers
Volume
11
Published Date
DOI
10.3390/cancers11020191

Cancer immunotherapy: harnessing the immune system to battle cancer.

The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer immunotherapy. These successes also underscore the importance of understanding basic tumor immunology for successful clinical translation in treating patients with cancer. The Reviews in this Review Series focus on current developments in cancer immunotherapy, highlight recent advances in our understanding of basic aspects of tumor immunology, and suggest how these insights can lead to the development of new immunotherapeutic strategies.
Authors
MLA Citation
Yang, Yiping. “Cancer immunotherapy: harnessing the immune system to battle cancer..” J Clin Invest, vol. 125, no. 9, Sept. 2015, pp. 3335–37. Pubmed, doi:10.1172/JCI83871.
URI
https://scholars.duke.edu/individual/pub1099160
PMID
26325031
Source
pubmed
Published In
J Clin Invest
Volume
125
Published Date
Start Page
3335
End Page
3337
DOI
10.1172/JCI83871

The role of natural regulatory T cells in infection.

Naturally occurring regulatory T cells (T(Reg)) suppress multiple cell types of the immune system to maintain dominant tolerance to protect from autoimmunity, down-modulate anti-tumor immunity and restrain allergic diseases. In addition to these functions, T(Reg) can alter effector responses to invading pathogens, leading to a variety of outcomes affecting both the host and infecting microorganisms. Here, we review how T(Reg) can influence the immune responses to chronic infections where pathogen-specific T(Reg) can contribute to pathogen persistence and, in some cases, concomitant immunity, as well as control immunopathology associated with robust immune responses. We also review the data on T(Reg) during acute infection, focusing on the questions these studies raise regarding the most appropriate model(s) to examine T(Reg) during infection. Finally, we discuss the ways in which the T(Reg) function can be altered by invading pathogens and how these can be exploited to develop methods therapeutically to influence disease and vaccine outcomes.
Authors
Sanchez, AM; Yang, Y
MLA Citation
Sanchez, Ana M., and Yiping Yang. “The role of natural regulatory T cells in infection..” Immunol Res, vol. 49, no. 1–3, Apr. 2011, pp. 124–34. Pubmed, doi:10.1007/s12026-010-8176-8.
URI
https://scholars.duke.edu/individual/pub807219
PMID
21116872
Source
pubmed
Published In
Immunol Res
Volume
49
Published Date
Start Page
124
End Page
134
DOI
10.1007/s12026-010-8176-8

Innate immune recognition of viruses and viral vectors.

Recombinant viral vectors such as adenovirus and adenovirus-associated virus have been used widely as vehicles for gene therapy applications because of the high efficiency with which they transfer genes into a wide spectrum of cells in vivo. However, enthusiasm for the use of viral vectors in gene therapy has been tempered by significant problems of attendant host cellular and humoral immune responses that limit their safety and efficacy in vivo. Advances in immunology have suggested a crucial role for the innate immune system in the induction of immune responses to viruses. Thus, a better understanding of the mechanisms by which the host's innate immune system recognizes viruses and viral vectors will help in the design of effective strategies to improve the outcome of viral vector-mediated gene therapy. In this review we first discuss our current understanding of innate immune recognition of viruses in general, and then focus on the innate immune responses to viral vectors for gene therapy.
Authors
MLA Citation
Huang, Xiaopei, and Yiping Yang. “Innate immune recognition of viruses and viral vectors..” Hum Gene Ther, vol. 20, no. 4, Apr. 2009, pp. 293–301. Pubmed, doi:10.1089/hum.2008.141.
URI
https://scholars.duke.edu/individual/pub777569
PMID
19272012
Source
pubmed
Published In
Hum Gene Ther
Volume
20
Published Date
Start Page
293
End Page
301
DOI
10.1089/hum.2008.141

Warfarin-induced skin necrosis in a patient with a mutation of the prothrombin gene.

Authors
Yang, Y; Algazy, KM
MLA Citation
Yang, Y., and K. M. Algazy. “Warfarin-induced skin necrosis in a patient with a mutation of the prothrombin gene..” N Engl J Med, vol. 340, no. 9, Mar. 1999. Pubmed, doi:10.1056/NEJM199903043400912.
URI
https://scholars.duke.edu/individual/pub807228
PMID
10068331
Source
pubmed
Published In
The New England Journal of Medicine
Volume
340
Published Date
Start Page
735
DOI
10.1056/NEJM199903043400912

Research Areas:

Acute Disease
Adaptive Immunity
Adenoviridae
Adenoviridae Infections
Adenovirus E1A Proteins
Adenovirus E1B Proteins
Adenoviruses, Human
Adjuvants, Immunologic
Adoptive Transfer
Aged
Alternative Splicing
Antibody Formation
Antigen Presentation
Antigens, CD4
Antigens, CD8
Antigens, Neoplasm
Antigens, Viral
Antineoplastic Agents
Autoantigens
Autoimmune Diseases
Autoimmunity
Blotting, Western
CD4 Antigens
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cell Proliferation
Chaperonins
Chloride Channels
Coculture Techniques
Combined Modality Therapy
Cyclic AMP
Cystic Fibrosis Transmembrane Conductance Regulator
Cytokines
Cytotoxicity, Immunologic
DNA, Viral
Dendritic Cells
Dependovirus
Disease Models, Animal
Electric Conductivity
Endoplasmic Reticulum
Endosomes
Extracellular Signal-Regulated MAP Kinases
Female
Flow Cytometry
Gene Deletion
Gene Knock-In Techniques
Gene Transfer Techniques
Gene therapy
Genes, Bacterial
Genes, Viral
Genetic Therapy
Germinal Center
Glucose
Graft vs Host Disease
Growth Inhibitors
HLA Antigens
HLA-C Antigens
Heat-Shock Proteins
Hemagglutinins
Hematologic Neoplasms
Hematopoietic Stem Cell Transplantation
Heparitin Sulfate
Histocompatibility
Histocompatibility Testing
Humans
Immune System
Immune Tolerance
Immunity, Cellular
Immunity, Innate
Immunologic Memory
Immunosuppressive Agents
Immunotherapy
Influenza A virus
Interferon Type I
Interferon-beta
Interleukin-10
Interleukin-12
Interleukin-13
Interleukin-2
Interleukin-6
Killer Cells, Natural
Luciferases
Lung Neoplasms
Lymphocyte Activation
Lymphocyte Depletion
Lymphocyte Transfusion
Lymphocytes
Lymphoma
Lymphopenia
Macrophages
Male
Membrane Glycoproteins
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Knockout
Mice, Mutant Strains
Mice, Nude
Mice, Transgenic
Microsomes
Middle Aged
Mitosis
Molecular Sequence Data
Myelodysplastic Syndromes
Myeloid Cells
Myeloid Differentiation Factor 88
NK Cell Lectin-Like Receptor Subfamily K
Neoplasms
North Carolina
Oocytes
Peripheral Blood Stem Cell Transplantation
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
RNA, Messenger
Receptors, Cell Surface
Receptors, Interleukin-1
Receptors, KIR
Recombinant Proteins
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Risk Factors
STAT1 Transcription Factor
Sequence Deletion
Stem Cell Transplantation
Survival Rate
T-Cell Antigen Receptor Specificity
T-Lymphocytes
T-Lymphocytes, Cytotoxic
T-Lymphocytes, Regulatory
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptor 8
Toll-Like Receptor 9
Toll-Like Receptors
Transfection
Transgenes
Transplantation Conditioning
Transplantation, Homologous
Tumor Escape
Vaccines
Vaccinia
Vaccinia virus
Virus Diseases
Viruses
Xenopus
beta-Galactosidase