Lim Endowed Chair of Dermatology Research
Director, Center for Cutaneous Biology and Immunology Research/Cancer Immunology Research Program, HFHS
Chair, Immunology Focus Group of WSU/KCI/HFHS
1 Ford Place, Rm 1D31
Detroit, MI 48202
DepartmentDept of Microbiology, Immunology and Biochemistry, Dept of Oncology
Cancer epigenetics (miRNAs and histone modification in skin cancer)
Epigenetic immunoregulation (NKT and gamma/delta T cell, dendritic cell, macrophage)
Cancer immunotherapy in human and mouse models (lung, breast and brain cancer)
Biomarkers for cancer early diagnosis and cancer immunotherapy response
Research in the Mi laboratory includes the epigenetic regulation in immune system and cancer development, and epigenetic biomarkers in precision medicine of cancer and autoimmune diseases. This spans from basic immunology and cancer biology research using different animal models (close to 100 mutant mouse strains in the Lab), to translational immunotherapy studies in cancer and autoimmune diseases using primary patient specimens.
- miRNAs regulate NKT cell development and function in cancer and autoimmunity. Natural killer T (NKT) cells are an evolutionarily conserved subset of T cells that are developmentally and functionally distinct from conventional T cells. Deficiencies in NKT cell number and function have been linked to the development of many diseases ranging from autoimmunity, cancer and infectious diseases. However, a significant gap remains in our understanding of how development and function of NKT cells are precisely regulated. MicroRNAs (miRNAs) are small non-coding RNAs that control essential biological functions and contribute to the development of many diseases. We were the first to report that the lack of miRNAs during hematopoiesis results in significantly reduced NKT cell number and impaired NKT cell maturation and function (Zhou L, PNAS, 2009), and identified the first miRNA, miR-150, that regulates NKT cell development and function (Zheng,Q, J Immunol, 2010). Using more than 30 different miRNA mutant mouse strains generated in the lab, we aim to reveal dynamic miRNA-mRNA regulation pathways that control NKT cell development and function. This will not only provide new insights into the biology of NKT cells, but also facilitate the development of more efficient NKT cell-based intervention strategies for cancer and autoimmunity, including CART-NKT therapy in cancer.
- HDACs regulate tissue resident macrophage/DC development and function in cancer. Histone deacetylases (HDACs) are enzymes that regulate gene expression by modifying chromatin structure through removal of acetyl groups from target histones or by directly deacetylating non-histone proteins, and represent a key epigenetic regulatory mechanism. HDAC inhibitors (HDIs) are shown to have anti-tumor and anti-inflammatory effects in a variety of diseases, in which macrophages and dendritic cells (DCs) play an important role. However, the mechanisms underlying the clinical effectiveness of HDIs remain largely unknown. We were the first to report that the inhibition of Class I/II HDACs by Trichostatin A (TSA) regulates the homeostasis and function of skin-resident DCs in vitro and in vivo. To evaluate the role of individual HDACs in tissue resident macrophage/DC development and function, we generated conditional tissue-specific HDAC knockout (KO) mice. Using these mouse models, we aim to uncover the epigenetic regulatory mechanisms of HDACs in tissue resident macrophage/DC development and function and to elucidate new mechanisms for HDI therapy in cancer, including the role of alveolar macrophages in lung cancer.
- miRNAs serve as the biomarkers for early diseases diagnose and immunotherapy response. There is an unmet need for new biomarkers of early diagnosis of cancer and autoimmune diseases. Discovery of predictive biomarkers for immunotherapy response is an important strategy to guide individual patients in the selection of appropriate therapies in the era of precision medicine. Using available biological samples from different cohorts of patients, our studies aim to identify specific serum miRNAs as biomarkers for early diagnosis of cancer and autoimmune Type 1 diabetes, and for the prediction of response to immunotherapy in cancer. The results from our studies may also facilitate the development of new intervention strategies for increasing immunotherapy in cancer.
Lu J, Hou X, Yuan X, Cui L, Liu Z, Li X, Ma L, Cheng X, Xin Y, Wang C, Zhang K, Wang X, Ren W, Sun R, Jia Z, Tian Z, Mi QS*, Li C*. Knockout of the urate oxidase gene provides a stable mouse model of hyperuricemia associated with metabolic disorders. Kidney Int. 2017 Jul 17. *Co-Senior
Liu Q, Zhang X, Yin C, Chen X, Zhang Z, Brown S, Xie H, Zhou L, Mi QS. HDAC4 is expressed on multiple T cell lineages but ispensable for their development and function. Oncotarget. 2017;8:17562-72.
Jin Y, Andersen G, Yorgov D, Ferrara TM, Ben S, Brownson KM, Holland PJ, Birlea SA, Siebert J, Hartmann A, Lienert A, van Geel N, Lambert J, Luiten RM, Wolkerstorfer A, Wietze van der Veen JP, Bennett DC, Taïeb A, Ezzedine K, Kemp EH, Gawkrodger DJ, Weetman AP, Kõks S, Prans E, Kingo K, Karelson M, Wallace MR, McCormack WT, Overbeck A, Moretti S, Colucci R, Picardo M, Silverberg NB, Olsson M, Valle Y, Korobko I, Böhm M, Lim HW, Hamzavi I, Zhou L, Mi QS, Fain PR, Santorico SA, Spritz RA. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nat Genet. 2016;48:1418-24.
Zhang X, Gu J, Yu FS, Zhou L, Mi QS. TGF-β1-induced transcription factor networks in Langerhans cell development and maintenance. Allergy. 2016;71:758-64.
Li C, Li Z, Liu S, Wang C, Han L, Cui L, Zhou J, Zou H, Liu Z, Chen J, Cheng X, Zhou Z, Ding C, Wang M, Chen T, Cui Y, He H, Zhang K, Yin C, Wang Y, Xing S, Li B, Ji J, Jia Z, Ma L, Niu J, Xin Y, Liu T, Chu N, Yu Q, Ren W, Wang X, Zhang A, Sun Y, Wang H, Lu J, Li Y, Qing Y, Chen G, Wang Y, Zhou L, Niu H, Liang J, Dong Q, Li X, Mi QS, Shi Y. Genome-wide association analysis identifies three new risk loci for gout arthritis in Han Chinese. Nat Commun. 2015;6:7041.
Zhou L, Shi YL, Li K, Hamzavi I, Gao TW, Huggins RH, Lim HW, Mi QS. Increased circulating Th17 cells and elevated serum levels of TGF-beta and IL-21 are correlated with human non-segmental vitiligo development. Pigment Cell Melanoma Res. 2015;28:324-9.
Chen WB, Gao L, Weiland M, Zhao J, Liu M, Zhou L, Mi QS. Deletion of miRNAs in bone marrow prevents streptozotocin-induced murine autoimmune diabetes but deletion of miR-155 does not. Cell Cycle. 2013;12:1151-2.
Xu YP, Shi Y, Cui ZZ, Jiang HH, Li L, Wang XF, Zhou L, Mi QS. TGFβ/Smad3 signal pathway is not required for epidermal Langerhans cell development. J Invest Dermatol. 2012;132:2106-9.
Zheng Q, Zhou L, Mi QS. MicroRNA miR-150 is involved in Vα14 invariant NKT cell development and function. J Immunol. 2012;188:2118-26.
Qi R, Weiland M, Gao XH, Zhou L, Mi QS. Identification of endogenous normalizers for serum microRNAs by microarray profiling: U6 small nuclear RNA is not a reliable normalizer. Hepatology. 2012;55:1640-2.
Post-Doc/Visiting Associate (1996-2000), Immunology Branch, National Institute on Aging/NIH
PhD (1992), China Medical University
MD (1985), Qilu Medical University (Former Taishan Medical College)
CB7410 Cancer Immunology and Immunotherapy