Zhang, B, Jia, Q, Bock, C, Chen, G, Yu, H, Ni, Q, Wan, Y, Li, Q, and Zhuang, Y. "Glimpse of natural selection of long-lived T-cell clones in healthy life." Proceedings of the National Academy of Sciences of the United States of America 113, no. 35 (August 17, 2016): 9858-9863.
Qi-Jing Li, PhD
To harness the unique immune-potentiating and immune-regulatory properties of T cells, it is of essence to understand and optimize T cell responses. As microRNAs (miRNAs) can serve as effective tools to manipulate a specific immune response, the major objective of my laboratory is to discover new immunoregulatory miRNAs and to employ them to modulate the strength and pattern of T cell responses for clinical intervention, especially, for cancer therapies. Stepping up to the challenges of this interdisciplinary field in its infancy, we have been constructing research programs by developing new technological platforms, fostering collaborations to acquire expertise in various disciplines, and focusing on the translational value of our projects.
Most projects in my laboratory are derived from the robust miRNA profiling platform developed in-house. Through the initial expression profiling, we have been working on key miRNAs as:
(I) non-invasive biomarkers for disease diagnosis and prognosis. Due to their high stability in bodily fluids and sensitivity of detection, miRNAs have the potential to serve as non-invasive disease biomarkers. Working collaboratively with several clinicians, we have identified miRNA signature panels to not only prognose AIDS progression, but also diagnose lung cancer and predict patient responsiveness to chemotherapy.
(II) entities/targets for immunotherapy. By elucidating the roles of specific miRNAs in T cell differentiation, effector function and tumor-immune crosstalk, my laboratory has unveiled multiple miRNA targets for immune-modulation and cancer immunotherapy;
(III) tools for discovery of novel epigenetic regulators that control T cell lineage commitment and plasticity. By studying the interplay between miRNAs and the epigenetic machinery, we have uncovered signaling nodes and protein functions that play previously-unappreciated roles in T cell fate decisions.
Seeking to understand regulatory mechanisms of T cell functions, ongoing work in my laboratory is based on two main foci. The first is to elucidate mechanisms of miRNA turnover during T cell activation. Although miRNAs are dramatically down-regulated upon TCR engagement, the underpinning molecular mechanisms and functional consequences of this dynamic turnover remain poorly-defined. To approach this question, we focused on machineries controlling intracellular vesicle trafficking. Proteomics analysis has helped us identify a new protein-interaction network between the vesicle sorting and miRNA machineries, which may direct intracellular trafficking of miRNAs. The second interest in my laboratory lies in developing miRNA-based immunotherapeutic strategies for cancer intervention. With the clinical relevance and translational value of our research in mind, immunotherapeutic miRNA candidates selected in our studies are first identified from expression profiling of lung cancer patient clinical samples, followed by further validation and characterization in various mouse models of cancer. Having identified several miRNA candidates, our efforts are currently invested in developing the relevant miRNA-targeting gene therapy tools to optimize the persistence and anti-tumor effector functions of both CD4+ and CD8+ T cells in vivo. In collaboration with clinicians at Duke, we are in the process of translating our findings into the clinic, by incorporating our miRNA-targeting moiety into chimeric antigen receptor cell therapy for glioblastoma patients.
Moving forward, while mechanistic aspects of our established research program will continue, new projects my laboratory will take on a more translational approach. With the support of our basic and clinical research colleagues at Duke, across the county, and in China, we will place greater emphasis on disease states; specifically, how miRNA molecules impact T cell responses during chronic viral infection or in the tumor microenvironment, and how these diseases condition the expression of key miRNAs.
Education and Training
- Graduate Research, University of California at Riverside, 1997 - 2002
- Research Assistant, Peking University (China), 1995 - 1997
- Ph.D., University of California at Riverside, 2002
- B.S., Peking University (China), 1996
Markowitz, GJ, Yang, P, Fu, J, Michelotti, GA, Chen, R, Sui, J, Yang, B, Qin, W-H, Zhang, Z, Wang, F-S, Diehl, AM, Li, Q-J, Wang, H, and Wang, X-F. "Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes." Cancer research 76, no. 8 (April 2016): 2394-2405.
Zhang, B, Liu, S-Q, Li, C, Lykken, E, Jiang, S, Wong, E, Gong, Z, Tao, Z, Zhu, B, Wan, Y, and Li, Q-J. "MicroRNA-23a Curbs Necrosis during Early T Cell Activation by Enforcing Intracellular Reactive Oxygen Species Equilibrium." Immunity 44, no. 3 (March 2016): 568-581.
Li, Y, Wang, Y, Zou, L, Tang, X, Yang, Y, Ma, L, Jia, Q, Ni, Q, Liu, S, Tang, L, Lin, R, Wong, E, Sun, W, Wang, L, Wei, Q, Ran, H, Zhang, L, Lian, H, Huang, W, Wu, Y, Li, Q-J, and Wan, Y. "Analysis of the Rab GTPase Interactome in Dendritic Cells Reveals Anti-microbial Functions of the Rab32 Complex in Bacterial Containment." Immunity 44, no. 2 (February 2016): 422-437.
Jia, Q, Zhou, J, Chen, G, Shi, Y, Yu, H, Guan, P, Lin, R, Jiang, N, Yu, P, Li, Q-J, and Wan, Y. "Diversity index of mucosal resident T lymphocyte repertoire predicts clinical prognosis in gastric cancer." OncoImmunology 4, no. 4 (April 3, 2015): e1001230-e1001230.
Lin, R, Chen, L, Chen, G, Hu, C, Jiang, S, Sevilla, J, Wan, Y, Sampson, JH, Zhu, B, and Li, Q-J. "Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression." The Journal of clinical investigation 124, no. 12 (December 2014): 5352-5367.
Li, C, Jiang, S, Liu, S-Q, Lykken, E, Zhao, L-T, Sevilla, J, Zhu, B, and Li, Q-J. "MeCP2 enforces Foxp3 expression to promote regulatory T cells' resilience to inflammation." Proceedings of the National Academy of Sciences of the United States of America 111, no. 27 (July 2014): E2807-E2816.
Liu, S-Q, Jiang, S, Li, C, Zhang, B, and Li, Q-J. "miR-17-92 cluster targets phosphatase and tensin homology and Ikaros Family Zinc Finger 4 to promote TH17-mediated inflammation." The Journal of biological chemistry 289, no. 18 (May 2014): 12446-12456.
Jiang, S, Li, C, McRae, G, Lykken, E, Sevilla, J, Liu, S-Q, Wan, Y, and Li, Q-J. "MeCP2 reinforces STAT3 signaling and the generation of effector CD4+ T cells by promoting miR-124-mediated suppression of SOCS5." Science signaling 7, no. 316 (March 11, 2014): ra25-.
Li, C, Ebert, PJR, and Li, Q-J. "T cell receptor (TCR) and transforming growth factor β (TGF-β) signaling converge on DNA (cytosine-5)-methyltransferase to control forkhead box protein 3 (foxp3) locus methylation and inducible regulatory T cell differentiation." J Biol Chem 288, no. 26 (June 28, 2013): 19127-19139.
Zhang, Y, Yang, P, Sun, T, Li, D, Xu, X, Rui, Y, Li, C, Chong, M, Ibrahim, T, Mercatali, L, Amadori, D, Lu, X, Xie, D, Li, Q-J, and Wang, X-F. "miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis." Nat Cell Biol 15, no. 3 (March 2013): 284-294.
Zhang, Z-N, Xu, J-J, Fu, Y-J, Liu, J, Jiang, Y-J, Cui, H-L, Zhao, B, Sun, H, He, Y-W, Li, Q-J, and Shang, H. "Transcriptomic analysis of peripheral blood mononuclear cells in rapid progressors in early HIV infection identifies a signature closely correlated with disease progression." Clinical Chemistry 59, no. 8 (2013): 1175-1186.
Yang, P, Li, Q-J, Feng, Y, Zhang, Y, Markowitz, GJ, Ning, S, Deng, Y, Zhao, J, Jiang, S, Yuan, Y, Wang, H-Y, Cheng, S-Q, Xie, D, and Wang, X-F. "TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma." Cancer Cell 22, no. 3 (September 11, 2012): 291-303.
Jiang, S, Li, C, Olive, V, Lykken, E, Feng, F, Sevilla, J, Wan, Y, He, L, and Li, Q-J. "Molecular dissection of the miR-17-92 cluster's critical dual roles in promoting Th1 responses and preventing inducible Treg differentiation." Blood 118, no. 20 (November 17, 2011): 5487-5497.
Ebert, PJR, Li, Q-J, Huppa, JB, and Davis, MM. "Functional development of the T cell receptor for antigen." Progress in Molecular Biology and Translational Science 92, no. C (2010): 65-100.