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:

Targeting the Human Notch 2-BCR Axis: A Driver of B-Cell Hyper-Responsiveness in Active Chronic Graft-Versus Host Disease (cGVHD)

Authors
Poe, JC; Jia, W; Li, Z; Hakim, FT; Pavletic, SZ; Rose, JJ; Rizzieri, DA; Yang, Y; Chen, BJ; Green, M; Anand, S; Siebel, CW; Maillard, I; Chao, NJ; Sarantopoulos, S
MLA Citation
URI
https://scholars.duke.edu/individual/pub1123127
Source
wos
Published In
Blood
Volume
126
Published Date

NKT cells are essential for innate immune control of vaccinia viral infection in vivo

Authors
Novy, P; Yang, Y
MLA Citation
Novy, Patricia, and Yiping Yang. “NKT cells are essential for innate immune control of vaccinia viral infection in vivo.” Journal of Immunology, vol. 186, AMER ASSOC IMMUNOLOGISTS, Apr. 2011.
URI
https://scholars.duke.edu/individual/pub1150143
Source
wos
Published In
The Journal of Immunology
Volume
186
Published Date

The TLR9-MyD88 Pathway Is Critical for Adaptive Immune Responses to AAV Vectors in Gene Therapy

Authors
Zhu, J; Huang, X; Yang, Y
MLA Citation
Zhu, Jiangao, et al. “The TLR9-MyD88 Pathway Is Critical for Adaptive Immune Responses to AAV Vectors in Gene Therapy.” Molecular Therapy, vol. 17, NATURE PUBLISHING GROUP, 2009, pp. S296–S296.
URI
https://scholars.duke.edu/individual/pub1081749
Source
wos
Published In
Molecular Therapy
Volume
17
Published Date
Start Page
S296
End Page
S296

Immunotherapy of surgical malignancies.

Authors
Morse, MA; Lyerly, HK; Clay, TM; Abdel-Wahab, O; Chui, SY; Garst, J; Gollob, J; Grossi, PM; Kalady, M; Mosca, PJ; Onaitis, M; Sampson, JH; Seigler, HF; Toloza, EM; Tyler, D; Vieweg, J; Yang, Y
MLA Citation
Morse, Michael A., et al. “Immunotherapy of surgical malignancies.Curr Probl Surg, vol. 41, no. 1, Jan. 2004, pp. 15–132. Pubmed, doi:10.1016/S0011384003001321.
URI
https://scholars.duke.edu/individual/pub728405
PMID
14749625
Source
pubmed
Published In
Current Problems in Surgery
Volume
41
Published Date
Start Page
15
End Page
132
DOI
10.1016/S0011384003001321

Recombinant IL-12 prevents formation of blocking IgA antibodies to recombinant adenovirus and allows repeated gene therapy to mouse lung.

Enthusiasm for the use of recombinant adenoviruses in gene therapy has been tempered by the problematic immune responses that develop to the virus and virus-infected cells. Humoral immune responses to the input viral proteins generate neutralizing antibodies that thwart attempts to effectively administer the therapy more than once. Previous studies in murine models of gene therapy for cystic fibrosis (CF) have shown that the formation of adenoviral antibodies of the IgA subtype, a process that is dependent on T helper cells of the TH2 subset, contributes to a block in gene transfer that occurs following a second administration of virus. We show in this report that coadministration of interferon-gamma (IFN-gamma) (or interleukin-12, which activates TH1 cells to secrete IFN-gamma) with the recombinant adenovirus into the airway of C57BL/6 mice diminishes the activation of TH2 cells and formation of neutralizing antibody, allowing for efficient readministration of recombinant virus. This suggests a strategy for gene therapy of CF in which administration of a short-acting immune modulator at the time of gene therapy may be sufficient to overcome the problems of humoral immunity.
Authors
Yang, Y; Trinchieri, G; Wilson, JM
URI
https://scholars.duke.edu/individual/pub807246
PMID
7585213
Source
pubmed
Published In
Nature Medicine
Volume
1
Published Date
Start Page
890
End Page
893

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