Department of Microbiology and Immunology
Jennifer Wu, PhD
1996-200 PhD, University of British Columbia, Vancouver, Canada
2000-2002 Postdoctoral Fellow, Fred Hutchinson Cancer Research Center
Office - HCC HO-612B
Lab - HCC HO-610
Research in my laboratory is focused on the molecular and cellular regulation of host immunity and inflammatory responses in tumor microenvironment by tumor secretive soluble elements, with emphasis on tumor shed proteins and secretive cytokines. One of mechanisms conveying tumor immune surveillance in cancer patients is though induced expression of the membrane-bound MHC I chain related molecules A and B (MICA and MICB) on tumor cell surface. These molecules serve as ligands for the immune activating receptor NKG2D to signal the activation of NK and CD8 T cell anti-tumor responses. In cancer patients with advanced diseases, cancer cells shed the membrane-bound MICA and MICB to produce immune suppressive soluble forms of sMICA and sMICB. Our research focuses are: 1) to elucidate the molecular mechanisms by which tumor shed MIC through a variety of genetically mutated cell lines and to define the optimal strategy to target tumor shedding; 2) to investigate how tumor shedding may shift the balance of anti-tumor immunity and pro-tumorigenic inflammation through the NKG2D receptor mediated cross-talks among immune/inflammatory cell types using the transgenic animal models established in my laboratory; 3) to harness NKG2D-mediated tumor immunity for cancer immunotherapy. Our laboratory has developed unique transgenic animal models and reagents for these studies.
The other interested area in my research is to investigate how the pleiotropic cytokine IL-6 in tumor microenvironment may regulate the balance of anti-tumor immunity and pro-tumorigenic inflammation. We are particularly interested in addressing: 1) how IL-6 may regulate tumor susceptibility to NK and T cell activation? 2) how to target IL-6 signaling in tumor microenvironment to achieve maximum anti-tumor immune/inflammatory response at cellular and systemic level? We have established a serial of IL-6 expressing tumor cell lines and tissue-specific IL-6 transgenic animals to address these questions.
Recent Publications | Additional Publications
Gang L, X Wang, X Zhang, N M Greenberg, and JD Wu. The genesis and progression of prostate cancer in an autochthonous genetically engineered mouse model is facilitated by expression of tumor-associated soluble NKG2D ligand while inhibited by a non-soluble membrane-restricted form. (submitted)
Gang L, XX Zhang, and JD Wu. Enforced expression of IL-6 in the prostate tips local microenvironment and susceptibility to tumorigeneisis (submitted)
Rojas A, G Liu, I Colemen, P Nelson, PB Fisher, SR Plymate, M Zhang, and JD Wu. IL-6 induces EMT and malignant transformation of benign prostate epithelial cells through autocrine loop and activation of IGF-IR. Oncogene 30(20):2345-55, 2011.
Page ST, D Lin, EA Mostaghel, B Brett Marck, J Wright, JD Wu, JK Amory, PS Nelson, and AM Matsumoto. Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen receptor action in healthy men: a randomized-controlled trial. J Clin Endocrinol Metab 96(2):430-7, 2011
Leung M, S Florczyk, F Kievit, O Veiseh, JD Wu, J Park, and M Zhang. Three-Dimensional Porous Chitosan-Alginate Scaffolds as an in vitro Model for Hepatocellular Carcinoma Tumor Microenvironment. Pharm Res 27(9):1939-48., 2010.
Liu G, CL Atteridge, AD Lundgren, X Wang, and JD Wu. The Membrane Type Matrix Metalloproteinase MMP14 Mediates Shedding of MICA independent of ADAMs. J Immunology 184 (7): 3346-50, 2010.
Wang X, AD Lundgren, P Singh, DR Goodlett, SR Plymate, and JD Wu. An six-amino acid motif in the alpha3 domain of MICA is the cancer therapeutic target to inhibit shedding. Biochem Biophys Res Commun 87:476-81, 2009.
Sprenger CC, K Haugk, S Sun, I Coleman, PS Nelson, RL Vessella, DL Ludwig, JD Wu, and SR Plymate. Transforming growth factor-beta-stimulated clone-22 (TSC-22) is an androgen and insulin-like growth factor (IGF) regulated gene in prostate epithelium. Clin Cancer Res. 15: 7634-7641, 2009.
Wu JD, DW Lin, ST Page, KL Atteridge, LD True, and SR Plymate. Oxidative DNA Damage in the Prostate May Predispose Men to a Higher Risk of Prostate Cancer. Translational Oncology. 2: 39-45, 2009
Wu JD, K Atteridge, XJ Wang, T Seya, and SR Plymate. Obstructing Shedding of the Immune Stimulatory MICB Prevents Tumor Formation: Implication for Targeted Cancer Therapy Clin. Can. Res.15:632-40, 2009.
Plymate SR, K Haugk, I Coleman, L Woodke, R Vessella, P Nelson, RB Montgomery, DL Ludwig, and JD Wu. An antibody targeting the type I insulin-like growth factor receptor enhances the castration-induced response in androgen-dependent prostate cancer. Clin Cancer Res 2007; 13:6429-39.
Wu JD, K Haugk, L Woodke, P Nelson, I Coleman, and SR Plymate. Interaction of IGF Signaling and the Androgen Receptor in Prostate Cancer Progression. Review. JCB 99:392-401, 2006.
Page ST, SR Plymate, WJ Bremner, DL Hess, AM Matsumoto, DL Lin, and JD Wu. Effects of Medical Castration and Testosterone Replacement on CD4+CD25+ Regulatory T cells, CD8+ T-cell IFN Expression and NK cells: Evidence for Physiological role of Testosterone and/or Its Metabolites in Cellular Immune Function. Am J Physiol Endocrinol Metab 290:E856-E863, 2006.
Wu JD, K Haugk, LM Higgins, R Vessella, RB Montgomery, DL Ludwig, and SR Plymate. Te Anti-IGF-IR Antibody A12 Enhances Docetaxel Activity Against Androgen-independent Xenograft Human Prostate Tumors. Clin. Cancer Research 12: 6153-60, 2006.
Title: Inhibition of MIC shedding to revive host NKG2D tumor immunity in cancer progression.
Funding Period: 07/01/2010-06/30/2015
Title: Modeling MIC shedding in prostate cancer.
Funding period: 10/01/2005 – 8/30/2011