Olive, V, Bennett, MJ, Walker, JC, Ma, C, Jiang, I, Cordon-Cardo, C, Li, Q-J, Lowe, SW, Hannon, GJ, and He, L. "miR-19 is a key oncogenic component of mir-17-92." Genes Dev 23, no. 24 (December 15, 2009): 2839-2849.
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
Ebert, PJR, Jiang, S, Xie, J, Li, Q-J, and Davis, MM. "An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a." Nat Immunol 10, no. 11 (November 2009): 1162-1169.
Li, Q-J, Chau, J, Ebert, PJR, Sylvester, G, Min, H, Liu, G, Braich, R, Manoharan, M, Soutschek, J, Skare, P, Klein, LO, Davis, MM, and Chen, C-Z. "miR-181a is an intrinsic modulator of T cell sensitivity and selection." Cell 129, no. 1 (April 6, 2007): 147-161.
Davis, MM, Krogsgaard, M, Huse, M, Huppa, J, Lillemeier, BF, and Li, Q-J. "T cells as a self-referential, sensory organ." Annu Rev Immunol 25 (2007): 681-695. (Review)
Krogsgaard, M, Li, Q-J, Sumen, C, Huppa, JB, Huse, M, and Davis, MM. "Agonist/endogenous peptide-MHC heterodimers drive T cell activation and sensitivity." Nature 434, no. 7030 (March 10, 2005): 238-243.
Li, Q-J, Dinner, AR, Qi, S, Irvine, DJ, Huppa, JB, Davis, MM, and Chakraborty, AK. "CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse." Nat Immunol 5, no. 8 (August 2004): 791-799.
Li, Q-J, Yao, M, Wong, W, Parpura, V, and Martins-Green, M. "The N- and C-terminal peptides of hIL8/CXCL8 are ligands for hCXCR1 and hCXCR2." FASEB J 18, no. 6 (April 2004): 776-778.
Li, Q-J, Yang, S-H, Maeda, Y, Sladek, FM, Sharrocks, AD, and Martins-Green, M. "MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300." EMBO J 22, no. 2 (January 15, 2003): 281-291.
Feugate, JE, Li, Q, Wong, L, and Martins-Green, M. "The cxc chemokine cCAF stimulates differentiation of fibroblasts into myofibroblasts and accelerates wound closure." J Cell Biol 156, no. 1 (January 7, 2002): 161-172.
Li, QJ, Vaingankar, S, Sladek, FM, and Martins-Green, M. "Novel nuclear target for thrombin: activation of the Elk1 transcription factor leads to chemokine gene expression." Blood 96, no. 12 (December 1, 2000): 3696-3706.
Li, Q, Vaingankar, SM, Green, HM, and Martins-Green, M. "Activation of the 9E3/cCAF chemokine by phorbol esters occurs via multiple signal transduction pathways that converge to MEK1/ERK2 and activate the Elk1 transcription factor." J Biol Chem 274, no. 22 (May 28, 1999): 15454-15465.