Department / Division:
Medicine / Medical Oncology

Address:
DUMC 103005
Durham, NC 27710

Appointment Telephone:
919-684-8964

Office Telephone:
919-684-8964

Fax Telephone:
919-684-5325

• MD, Zhejiang Medical University (China), 1985

• Internal Medicine, University of Pennsylvania School of Medicine, 1996-1999

• Medical Oncology, Johns Hopkins Oncology Center (Maryland), 1999-2002

• PhD, Molecular and Cell Biology, University of Michigan, 1990-1993

Clinical Interests:
Lymphoma and virus-associated malignancies

Research Interests:
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 (T_Reg) play a critical role in the suppression of anti-tumor immunity.  However, little is known about how T_Reg suppress T cell activation in vivo. Delineation of mechanisms underlying T_Reg-mediated suppression in vivo will help develop strategies to overcome T_Reg-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.

Representative Publications:
Zhu J, Huang X, and Yang Y: The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice. J. Clin. Invest. 2009; doi:10.1172/JCI37607. (2009)

Quigley M, Martinez J, Huang X, and Yang Y: A critical role for direct TLR2-MyD88 signaling in CD8 T cell clonal expansion and memory formation following vaccinia viral infection. Blood 2009; 113:2256-2264. (2009)

Huang X and Yang Y: Innate immune recognition of viruses and viral vectors. Hum. Gene Ther. 2009; 20:293-301. (2009)

Horkheimer I, Quigley M, Zhu J, Huang X, Chao N and Yang Y: Induction of type I IFN is required for overcoming tumor-specific T cell tolerance after stem cell transplantation. Blood 2009; 113:5330-5339. (2009)

Zhu J, Huang X, and Yang Y: A critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo. Mol. Ther. 2008; 16:1300-1307 (2008)

Quigley M, Huang X, and Yang Y: STAT1 signaling in CD8 T cells is required for their clonal expansion and memory formation following viral infection in vivo. J. Immunol. 2008; 180:2158-2164. (2008)

Martinez J, Huang X, and Yang Y: Direct action of type I IFN on NK cells is required for their activation in response to vaccinia viral infection in vivo. J. Immunol. 2008; 180:1592-1597. (2008)

Zhu J, Martinez J, Huang X, and Yang Y: Innate immunity against vaccinia virus is mediated by TLR2 and requires TLR-independent production of IFN-β. Blood 2007; 109:619-625. (2007)

Zhu J, Huang X, and Yang Y: Type I IFN signaling on both B and CD4 T cells is required for protective antibody response to adenovirus. J. Immunol. 2007; 178:3505-3510. (2007)

Zhu J, Huang X, and Yang Y: Innate immune response to adenoviral vectors is mediated by both TLR-dependent and -independent pathways. J. Virol. 2007; 81:3170-3180. (2007)

Quigley M, Huang X, and Yang Y: Extent of stimulation controls the formation of memory CD8 T cells. J. Immunol. 2007; 179:5768-5777. (2007)

Novy P, Quigley M, Huang X, and Yang Y: CD4 T cell help is required for CD8 T cell survival during primary and secondary responses. J. Immunol. 2007; 179:8243-8251. (2007)

Huang X and Yang Y: The fate of effector CD8 T cells in vivo is controlled by the duration of antigen stimulation. Immunology 2006; 118:361-371. (2006)

Huang X, Zhu J, and Yang Y: Protection against autoimmunity in nonlymphopenic hosts by CD4⁺CD25⁺ regulatory T cells is antigen-specific and requires IL-10 and TGF-β. J. Immunol. 2005; 175:4283-4291. (2005)

Yang Y, Huang C-T, Huang X, and Pardoll DM: Persistent Toll-like receptor signals are required for reversing regulatory T cell-mediated CD8 tolerance. Nature Immunology 2004; 5:508-515. (2004)

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, and Yang Y: How does the immune system attack cancer? Curr. Probl. Surg. 2004; 41:15-132. (2004)

Huang X and Yang Y: Transient gain of effector function by CD8⁺ T cells undergoing peripheral tolerance to high-dose self-antigen. Eur. J. Immunol. 2004; 34:1351-1360. (2004)

Yang Y and Algazy KM: Warfarin-induced skin necrosis in a patient with a mutation of the prothrombin gene. New Engl. J. Med. 1999; 340:735. (1999)

Yang Y and Wilson JM: CD40 ligand-dependent T cell activation: requirement of B7-CD28 signaling through CD40. Science 1996; 273:1862-1864. (1996)

Yang Y, Xiang Z, Ertl HC, and Wilson JM: Upregulation of class I major histocompatibility complex antigens by interferon-γ is necessary for T-cell-mediated elimination of recombinant adenovirus-infected hepatocytes in vivo. Proc. Natl. Acad. Sci. USA 1995; 92:7257-7261. (1995)

Yang Y, Trinchieri G, and Wilson JM: Recombinant IL-12 prevents formation of blocking IgA antibodies to recombinant adenovirus and allows repeated gene therapy to mouse lung. Nature Medicine 1995; 1:890-893. (1995)

Yang Y, Nunes FA, Berencsi K, Gonczol E, Engelhardt JF, and Wilson JM: Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosis. Nature Genetics 1994; 7:362-369. (1994)

Yang Y, Nunes FA, Berencsi K, Furth EE, Gonczol E, and Wilson JM: Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proc. Natl. Acad. Sci. USA 1994; 91:4407-4411. (1994)

Yang Y, Ertl HC, and Wilson JM: MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses. Immunity 1994; 1:433-442. (1994)

Yang Y, Raper SE, Cohn JA, Engelhardt JF, and Wilson JM: An approach for treating the hepatobiliary disease of cystic fibrosis by somatic gene transfer. Proc. Natl. Acad. Sci. USA 1993; 90:4601-4605. (1993)

Yang Y, Janich S, Cohn JA, and Wilson JM: The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi nonlysosomal compartment. Proc. Natl. Acad. Sci. USA 1993; 90:9480-9484. (1993)