|Assistant Professor, Microbiology, Immunology & Molecular Genetics|
|Member, CTSI, Cell & Developmental Biology GPB Home Area, Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, Immunity, Microbes & Molecular Pathogenesis GPB Home Area, Molecular Pharmacology GPB Home Area|
Our overall interest is to decipher the molecular mechanisms responsible for productive or defective immune responses against chronic diseases like cancer and exploit knowledge to design effective therapeutic strategies with potential clinical applications. We have three major research directions:
1. Mechanisms of immune surveillance and suppression in cancer
This research goal is to dissect the cellular and molecular mechanisms that control the immune surveillance and suppression in cancer. In particular, we are interested in studying the molecular control of the functional interactions among innate immune cells (including dendritic cells, macrophages, natural killer cells, and neutrophils), T cells, and tumor cells in the tumor microenvironment. We will primarily focus on studying dendritic cells (DCs) and T cells, and will initially study the roles of two groups of molecules: NF-κB and microRNAs.
2. Engineering immune cells against cancer
Along this research direction, we will explore the genetic engineering of T cells, dendritic cells (DCs), natural killer (NK) cells and invariant natural killer T (iNKT) cells for treating cancer in pre-clinical animal models. Strategies include providing the immune cells with tumor-recognition specificity and enhancing their tumor-fighting capacity.
3. Engineering stem cells against cancer
Building on our previous success in genetically programming blood stem cells to develop into tumor-killer T cells and invariant natural killer T (iNKT) cells, we will further explore engineering blood stem cells, pluripotent stem cells and induced pluripotent stem (iPS) cells to generate immune cells battling cancer.
The immune system comprises a small, powerful network of blood cells that survey, detect and destroy almost all harmful invasions by germs or viruses but it often is unable to fight against deadly diseases such as cancer and HIV/AIDS. Lili Yang, PhD, seeks to understand how the immune system responds to attack by disease. Through her research, Dr. Yang hopes to develop effective therapies that will engineer the immune system of patients suffering from cancer and AIDS by manipulating their own blood cells to fight their diseases.
Our bodies often do not mount an immune response to cancer because the disease is the uncontrolled division of our own cells. Dr. Yangs earlier research showed that immune cells, including hematopoietic (blood) stem cells, T cells and dendritic cells can be engineered to promote an immune response against disease. Her current research builds upon her past work on the immune system monitoring of and interaction with cancer cells, the suppression of the immune response against cancer, and ultimately, the translation of these discoveries into clinical uses such as engineering the immune system to fight cancer.
Dr. Yangs research is collaborative involving a multi-disciplinary and multi-institutional research group called the Translational Consortium in Engineered Immunity. The group includes UCLA scientists and clinicians as well as researchers from California Institute of Technology (Caltech), University of Southern California (USC), and the City of Hope.
Dr. Yang arrived at UCLA in January 2013 as a member the Broad Stem Cell Research Center and an assistant professor of Microbiology, Immunology and Molecular Genetics (MIMG). Previously, she worked with Nobel laureate Dr. David Baltimore as lead scientist and project manager of the Engineering Immunity Program in the Division of Biology at Caltech.
Dr. Yang received her bachelors degree at the University of Science & Technology of China, her masters degree at UC Riverside, and her doctorate at Caltech. Her research is funded by the National Institutes of Health, the California Institute for Regenerative Medicine (CIRM), and various UCLA entities including the Department of Microbiology, Immunology and Molecular Genetics (MIMG), the Broad Stem Cell Research Center (BSCRC), the Clinical and Translational Science Institute, and the Jonsson Comprehensive Cancer Center.
Smith, D. J.; Liu, S.; Ji, S.; Li, B.; McLaughlin, J.; Cheng, D.; Witte, O. N.; Yang, L. Genetic engineering of hematopoietic stem cells to generate invariant natural killer T cells. Proc Natl Acad Sci U S A. 2015; 112(5): 1523-8.
Yang, L.; Wang, P. Passive immunization against HIV/AIDS by antibody gene transfer. Viruses. 2014; 6(2): 428-47.
Chodon, T.; Comin-Anduix, B.; Chmielowski, B.; Koya, R. C.; Wu, Z.; Auerbach, M.; Ng, C.; Avramis, E.; Seja, E.; Villanueva, A.; McCannel, T. A.; Ishiyama, A.; Czernin, J.; Radu, C. G.; Wang, X.; Gjertson, D. W.; Cochran, A. J.; Cornetta, K.; Wong, D. J.; Kaplan-Lefko, P.; Hamid, O.; Samlowski, W.; Cohen, P. A.; Daniels, G. A.; Mukherji, B.; Yang, L.; Zack, J. A.; Kohn, D. B.; Heath, J. R.; Glaspy, J. A.; Witte, O. N.; Baltimore, D.; Economou, J. S.; Ribas, A. Adoptive transfer of MART-1 T-cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma. Clin Cancer Res. 2014; 20(9): 2457-65.
Yu, K. K.; Aguilar, K.; Tsai, J.; Galimidi, R.; Gnanapragasam, P.; Yang, L.; Baltimore, D. Use of mutated self-cleaving 2A peptides as a molecular rheostat to direct simultaneous formation of membrane and secreted anti-HIV immunoglobulins. PLoS One. 2012; 7(11): e50438.
Yang, L.; Boldin, M. P.; Yu, Y.; Liu, C. S.; Ea, C. K.; Ramakrishnan, P.; Taganov, K. D.; Zhao, J. L.; Baltimore, D. miR-146a controls the resolution of T cell responses in mice. J Exp Med. 2012; 209(9): 1655-70.
Hur, E. M.; Patel, S. N.; Shimizu, S.; Rao, D. S.; Gnanapragasam, P. N.; An, D. S.; Yang, L.; Baltimore, D. Inhibitory effect of HIV-specific neutralizing IgA on mucosal transmission of HIV in humanized mice. Blood. 2012; 120(23): 4571-82.
Xiao, L.; Kim, J.; Lim, M.; Dai, B.; Yang, L.; Reed, S. G.; Baltimore, D.; Wang, P. A TLR4 agonist synergizes with dendritic cell-directed lentiviral vectors for inducing antigen-specific immune responses. Vaccine. 2012; 30(15): 2570-81.
Balazs, A. B.; Chen, J.; Hong, C. M.; Rao, D. S.; Yang, L.; Baltimore, D. Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature. 2012; 481(7379): 81-4.
Yang, L.; Yu, Y.; Kalwani, M.; Tseng, T. W.; Baltimore, D. Homeostatic cytokines orchestrate the segregation of CD4 and CD8 memory T-cell reservoirs in mice. Blood. 2011; 118(11): 3039-50.
Boldin, M. P.; Taganov, K. D.; Rao, D. S.; Yang, L.; Zhao, J. L.; Kalwani, M.; Garcia-Flores, Y.; Luong, M.; Devrekanli, A.; Xu, J.; Sun, G.; Tay, J.; Linsley, P. S.; Baltimore, D. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med. 2011; 208(6): 1189-201.
Luo, X. M.; Lei, M. Y.; Feidi, R. A.; West, A. P., Jr.; Balazs, A. B.; Bjorkman, P. J.; Yang, L.; Baltimore, D. Dimeric 2G12 as a potent protection against HIV-1. PLoS Pathog. 2010; 6(12): e1001225.
O'Connell, R. M.; Balazs, A. B.; Rao, D. S.; Kivork, C.; Yang, L.; Baltimore, D. Lentiviral vector delivery of human interleukin-7 (hIL-7) to human immune system (HIS) mice expands T lymphocyte populations. PLoS One. 2010; 5(8): e12009.
Baltimore, D.; Witte, O. N.; Yang, L.; Economou, J.; Ribas, A. Overcoming barriers to programming a therapeutic cellular immune response to fight melanoma. Pigment Cell Melanoma Res. 2010; 23(2): 288-9.
Dai, B.; Yang, L.; Yang, H.; Hu, B.; Baltimore, D.; Wang, P. HIV-1 Gag-specific immunity induced by a lentivector-based vaccine directed to dendritic cells. Proc Natl Acad Sci U S A. 2009; 106(48): 20382-7.
Luo, X. M.; Maarschalk, E.; O'Connell, R. M.; Wang, P.; Yang, L.; Baltimore, D. Engineering human hematopoietic stem/progenitor cells to produce a broadly neutralizing anti-HIV antibody after in vitro maturation to human B lymphocytes. Blood. 2009; 113(7): 1422-31.
Chhabra, A.; Yang, L.; Wang, P.; Comin-Anduix, B.; Das, R.; Chakraborty, N. G.; Ray, S.; Mehrotra, S.; Yang, H.; Hardee, C. L.; Hollis, R.; Dorsky, D. I.; Koya, R.; Kohn, D. B.; Ribas, A.; Economou, J. S.; Baltimore, D.; Mukherji, B. CD4+CD25- T cells transduced to express MHC class I-restricted epitope-specific TCR synthesize Th1 cytokines and exhibit MHC class I-restricted cytolytic effector function in a human melanoma model. J Immunol. 2008; 181(2): 1063-70.
Ziegler, L.; Yang, L.; Joo, Ki; Yang, H.; Baltimore, D.; Wang, P. Targeting lentiviral vectors to antigen-specific immunoglobulins. Hum Gene Ther. 2008; 19(9): 861-72.
Yang, L.; Yang, H.; Rideout, K.; Cho, T.; Joo, K. I.; Ziegler, L.; Elliot, A.; Walls, A.; Yu, D.; Baltimore, D.; Wang, P. Engineered lentivector targeting of dendritic cells for in vivo immunization. Nat Biotechnol. 2008; 26(3): 326-34.
Yang, L.; Bailey, L.; Baltimore, D.; Wang, P. Targeting lentiviral vectors to specific cell types in vivo. Proc Natl Acad Sci U S A. 2006; 103(31): 11479-84.
Yang, L.; Baltimore, D. Long-term in vivo provision of antigen-specific T cell immunity by programming hematopoietic stem cells. Proc Natl Acad Sci U S A. 2005; 102(12): 4518-23.
Yang, L.; Qin, X. F.; Baltimore, D.; Van Parijs, L. Generation of functional antigen-specific T cells in defined genetic backgrounds by retrovirus-mediated expression of TCR cDNAs in hematopoietic precursor cells. Proc Natl Acad Sci U S A. 2002; 99(9): 6204-9.
Yang, L.; Kuo, C. B.; Liu, Y.; Coss, D.; Xu, X.; Chen, C.; Oster-Granite, M. L.; Walker, A. M. Administration of unmodified prolactin (U-PRL) and a molecular mimic of phosphorylated prolactin (PP-PRL) during rat pregnancy provides evidence that the U-PRL:PP-PRL ratio is crucial to the normal development of pup tissues. J Endocrinol. 2001; 168(2): 227-38.
Bridges, R.; Rigero, B.; Byrnes, E.; Yang, L.; Walker, A. Central infusions of the recombinant human prolactin receptor antagonist, S179D-PRL, delay the onset of maternal behavior in steroid-primed, nulliparous female rats. Endocrinology. 2001; 142(2): 730-9.
Coss, D.; Yang, L.; Kuo, C. B.; Xu, X.; Luben, R. A.; Walker, A. M. Effects of prolactin on osteoblast alkaline phosphatase and bone formation in the developing rat. Am J Physiol Endocrinol Metab. 2000; 279(6): E1216-25.
Coss, D.; Kuo, C. B.; Yang, L.; Ingleton, P.; Luben, R.; Walker, A. M. Dissociation of Janus kinase 2 and signal transducer and activator of transcription 5 activation after treatment of Nb2 cells with a molecular mimic of phosphorylated prolactin. Endocrinology. 1999; 140(11): 5087-94.