1. Study the molecular and structural mechanisms of the epigenetic regulation on gene expression.
2. Understand the functional mechanisms of non-coding RNAs using the methods of structural biology.
Over the past decade, long non-coding RNAs (lncRNAs) have emerged as an important class of the genomic pervasive transcripts that are involved in a variety of biological functions in many model systems. Bioinformatic and high-throughput loss of function analyses suggest that lncRNAs add a critical layer of regulation on the gene expressions of diverse biological processes, ranging from stem cell pluripotency to tumorigenesis. Through the knowledge of the small number of well characterized lncRNAs to date, it’s realized that lncRNAs usually exist in the form of ribonucleoprotein complex (RNP), in which lncRNAs and the associated protein factors cooperate with each other to regulate their target genes. Chromatin modifiers and transcription factors are among the most common lncRNA-associated factors. Current studies on lncRNAs are primarily limited to the functional analyses of the entire RNP complexes. It remains elusive about the functional protein-RNA domains involved in the formation of lncRNPs as well as about how lncRNPs are assembled on their targets. Extensive biochemical and structural studies are required to address these questions. Our lab aims at understanding the coordinated functions of lncRNAs and their associated protein factors at the structural and mechanistic levels. Our current studies focus on several important lncRNAs that participate in embryogenesis and tumorigenesis.
1. Huang J, Brown A, Wu J, Xue J, Bley C, Rand D, Wu L, Zhang R, Chen J, Lei M. Structural basis for an essential protein-RNA recognition in telomerase. Nat Struct Mol Biol 21, 507-12 (2014).
2. Zhou H, Liu L, Huang J, Bernard D, Karatas H, Navarro A, Lei M, Wang S. Structure-based design of high-affinity macrocyclic peptidomimetics to block the Menin-Mixed Lineage Leukemia 1 (MLL1) protein-protein interaction. J Med Chem 56, 1113-23 (2013)
3. Huang J, Wan B, Wu L, Yang Y, Dou Y, Lei M. Structural insight into the regulation of MOF in the male-specific lethal complex and the non-specific lethal complex. Cell Res. 6, 1078-81 (2012)
4. Huang J, Gurung B, Wan B, Matkar S, Veniaminova NA, Wan K, Merchant JL, Hua X, Lei M. The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature 482, 542-6 (2012)
5. Thiel AT, Huang J, Lei M, Hua X. Menin as a hub controlling mixed lineage leukemia. Bioessays 34, 771-80 (2012)
6. Zeng Z, Min B, Huang J, Hong K, Yang Y, Collins K, Lei M. Structural basis for Tetrahymena telomerase processivity factor Teb1 binding to single-stranded telomeric-repeat DNA. Proc Natl Acad Sci U S A 108, 20357-61 (2011)
Education Background & Academic Experience
2000-2004: B.S. in Biotechnology, Shandong University, Jinan, China
2004-2009: Ph.D. in Biology, Tsinghua University, Beijing, China
2009-2014: Postdoctoral Research Associate, Department of Biological Chemistry, University of Michigan, Howard Hughes Medical Institute, Ann Arbor, MI, USA
2014-present: Professor, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China