Profile

Laboratory of Immune Regulation

Research Interests: The main focus of this newly established lab is to elucidate the molecular pathways and cellular interactions that mediate and regulate immune response including both innate and T cell mediated immune response by using molecular biology and genetic approaches. We are especially interested in the identification and characterization of novel immune-related genes and the development and treatment of autoimmune diseases.

Main approaches used: molecular biology approaches, gene knock-out, cell culture, mouse model of autoimmune diseases

Ongoing projects:

1. TLR-induced signal transduction and gene expression regulation: We’ve identified a group of genes which can be induced by the activation of TLR4 receptor on the surface of dendritic cells and macrophages by using bioinformatics and genomics technology. Ongoing functional analysis of this genes involved in TLR signaling or antigen presentation cell maturation will allow us further understand the regulation mechanism of this process.

2. The role of NK and CD8 regulatory cell in autoimmune disease and cancer immunology:
We’ve been working on mouse EAE model (a model for human multiple sclerosis) and found out that modulation of CD8 and NK function can significantly alter the progression of disease. We have found out that disruption of an interaction between CD94/NKG2A and its ligand Qa1 can promote the activation of NK cells and unleash the suppression activity of CD8 suppressor cells, which lead to a complete diminish of lethal EAE. Thus, the promotion of NK and CD8 regulatory cells activity by antibodies will be a potential treatment method for MS. We will also explore the combination of this antibody treatment with anti-4-1BB treatment, which has been shown to induce and activate a subset of CD11c positive CD8 suppressor cells, which we find also to be NKG2A positive.
The same idea will also be applied to other autoimmune disease models. In terms of anti-tumor immunity, the regulation of anti-Cancer CD8 response is facing the same problem as the CD8 suppressor cells described above due to the nature that they are also anti-self cells. Their function might be suppressed or tolerated by similar mechanism. The activation and expansion of CD8 T cells will facilitate the anti-tumor response.

3. The role of thymocytes-specific genes in T cell development and response:
The human genome project have exerts a lot of EST data in an accessible state which makes it possible to compare gene expression in different samples. By using data-mining techniques, we have identified some unknown genes specifically expressed in thymocytes and mature T lymphocytes. Further analysis of these immune-specific genes will allow us to find novel proteins involved in the regulation of T cell development and function.
Since many of the ESTs I have found from this data mining are RNAs that didn’t encode a protein, it will allow us to study the role of these non-coding RNAs in regulating lymphocytes differentiation. Non-coding RNAs like microRNAs have been shown to have an important regulatory function in many biological processes. This work might lead to further understanding of non-coding RNAs.

Selected Publications：

Wang D， Lou J, Ouyang C， Chen W， Liu Y， Liu X， Cao X， Wang J and Lu L, Rab10 facilitates TLR4 signaling by promoting replenishment of TLR4 onto the plasma membrane. PNAS 2010 107 (31) 13806-13811

Kim HJ, Verbinnen B, Tang X, Lu L, and Cantor H, Inhibition of follicular T helper cells by CD8+ Treg is essential for self tolerance. Nature 2010 (In Press)

Lu L, Kim H-J, Werneck M and Cantor H, Regulation of CD8+ Treg: Interruption of NKG2A- Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease. Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19420-5.

Lu L and Cantor H, Generation and Regulation of CD8+ Regulatory T Cells. Cell Mol Immunol. 2008, 5(6): 401-6.

Lu L, Ikizawa K, Hu D, Werneck MBF, Wucherpfennig KW, and Cantor H., Regulation of Activated CD4+ T Cells by NK Cells via the Qa-1–NKG2A Inhibitory Pathway, Immunity 2007,25(5): 593-604.

Lu L, Werneck M, Cantor H. 2006. The Immunoregulatory Effects of Qa1. Immunol Rev. 2006 Aug;212:51-9.(Pubmed)

Shinohara M, Lu L, Bu J, Werneck MBF, Kobayashi KS, Glimcher LH & Cantor H. Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells. Nat Immunol. 2006 May;7(5):498-506. (Pubmed)

Paust S, Lu L, McCarty N, Cantor H. Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc. Natl. Acad. Sci. USA, 2004; 101:10398-403. (Pubmed)

Lu L, Han A, Chen J-J. Translation Initiation Control by Heme-Regulated Eukaryotic Initiation Factor 2alpha Kinase in Erythroid Cells under Cytoplasmic Stresses” Mol. Cell. Biol. 2001;21: 7971-7980. (Pubmed)

Lu L, Zhu J, Zheng Z, Yan M, Xu W, Sun L, Theze J, Liu X. Jak-STAT pathway is involved in the induction of TNF-b gene during stimulation by IL-2. European Journal of Immunology 1998;28: 805-810. (Pubmed)