- Damon Runyon Postdoctoral Fellowship, 2009-2012
- Howard Hughes Medical Institute (HHMI) Fellow, 2009-2012
- K99/R00 Pathway to Independence Award, NICHD, 2012-2016
- 1R01NS096176, NINDS, 2016-2021
- Research Interests -
- Stem Cell, Neural Development and Neural degeneration
Our lab has a general interest in neural development and neurodegeneration. We ask how neural progenitor cell (NPC) balances its self-renewal and differentiation, and how neuron is formed and maintained. We study these questions in the contrext of normal brain development and neurological disorders. We mainly use mouse genetic, cellular, molecular and biochemical approaches.
Among the other projects being pursued in the lab are the following:
(I) RNA Mediated Regulation in Neural Progenitor Cells (NPCs) and Neural Development. We have discovered that microRNAs are essential for cell differentiation (Chen et al. Nat Genet, 2006; Chen et al. PNAS, 2008; Chen et al. JCB, 2010), but the RNA mediated regulation in stem/progenitor cell maintenance remains unclear. We recently found that RNA associated protein Lin41, Lin28, and miRNA cluster miR-302/367 control the balance of self-renewal and differentiation of NPCs (Chen et al. Genes & Dev, 2012; Yang, et al. Development, 2015; Yang, et al. Developmental Biology, 2015), whose disruption leads to neural tube defects (NTDs) and microcephaly in mice. We are continuing to explore these RNA regulatory networks in NPCs and brain development with the goal of uncovering new disease mechanisms.
(II) Disease mechanisms of neurodevelopmental disorders . One approach to understand neural biology is to study neurological disorders. Malformations of cortical development (MCDs), inlcuding microcephaly, represent a major cause of development disabilities and are at the root of numerous neurological disorders. Our recent studies on one Microcephaly gene WDR62 suggest a new disease mechanism for human microcephaly, which is that the mitotic progression but not spindle orientation defect of embryonic NSCs causes microcephaly with WDR62 mutations (Chen et al. Nature Communication, 2014). We are continuing to study WDR62 and other disease genes in order to advance our understanding of related disease mechanisms and neurobiology.
1. Shan L, Oh HS, Chen J, Guo M, Zhou J, Alfano JR, Collmer A, Jia X, Tang X (2004) The HopPtoF locus of Pseudomonas syringae pv. tomato DC3000 encodes a type III chaperone and a cognate effector. Molecular Plant-Microbe Interactions. May;17(5):447-55.
2. Jian-Fu Chen, Elizabeth M Mandel, J Michael Thomson, Qiulian Wu, Thomas E Callis, Scott M Hammond, Frank L Colon, Da-Zhi Wang (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nature Genetics. 38(2): 228-33. http://www.ncbi.nlm.nih.gov/pubmed/16380711
3. Tatsuguchi M, Seok HY, Callis TE, Thomson JM, Chen JF, Newman M, Rojas M, Hammond SM, Wang DZ (2007) Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy. Journal of Molecular and Cellular Cardiology. 42(6): 1137-41.
4. Callis TE, Chen JF, Wang DZ. (2007) MicroRNAs in skeletal and cardiac muscle development. DNA and Cell Biology. Apr;26(4):219-25.
5. Jian-Fu Chen, Elizabeth P. Murchison, Ruhang Tang, Michael D. Schneider, Craig H. Selzman, Gerhard Meissner, Gregory J. Hannon and Da-Zhi Wang (2008) Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proceedings of National Academy of Sciences. 12; 105(6): 2111-6. http://www.ncbi.nlm.nih.gov/pubmed/18256189
6. Jian-Fu Chen, Qiulian Wu, Shusheng Wang, Yiping Chen, and D.-Z. Wang (2008) Myocardin marks the earliest cardiac gene expression and plays an important role in heart development. The Anatomical Record. 291(10): 1200-11.
7. Callis TE, Deng Z, Chen JF, Wang DZ. (2008) Muscling through the microRNA world. Experimental Biology and Medicine (Maywood). Feb; 233(2):131-8.
8. Thomas E. Callis, Kumar Pandys, Hee Young Seok, Ru-Hang Tang, Mariko Tatsuguchi, Jian-Fu Chen, Bronwyn Gunn, Craig H. Selzman, Da-Zhi Wang (2009) MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. The Journal of Clinical Investigation. 119(9): 2772-2786.
9. Jian-Fu Chen, Wang DZ (2009) miRNAs and muscle disorders. Journal Cell Science. 122(Pt1): 13-20. http://www.ncbi.nlm.nih.gov/pubmed/19092056
10. Jian-Fu Chen, Yazhong Tao, Juan Li, Zhen Yan, Xiao Xiao, Da-Zhi Wang (2010) MicroRNA-1 and microRNA-206 regulate skeletal muscle satellite cell proliferation and differentiation by repressing Pax7. The Journal of Cell Biology. 190(5):867-79. http://www.ncbi.nlm.nih.gov/pubmed/20819939
11. Zhan-Peng Huang, Jian-Fu Chen, Jenna N. Regan, Colin T. Magurie, Ru-Hang Tang, Xiu-Rong Dong, Mark W. Majesky, Da-Zhi Wang (2010) Loss of microRNAs in neural crest leads to cardiovascular syndromes resembling human congenital heart defects. Arterioslerosis, Thrombosis, and Vascular Biology. 30(12): 2575-86.
12. Zhong-Liang Deng, Jian-Fu Chen, Da-Zhi Wang (2011) Transgenic overexpression of miR-133a in skeletal muscle. BMC Musculoskeletal Disorders. 12(1): 115.
13. Tao Y, Neppl RL, Huang ZP, Chen J, Tang RH, Cao R, Zhang Y, Jin SW, Wang DZ. (2011) The histone methyltransferase Set7/9 promotes myoblast differentiation and myofibril assembly. The Journal of Cell Biology. Aug 22;194 (4):551-65.
14. Huang ZP, Young Seok H, Zhou B, Chen J, Chen JF, Tao Y, Pu WT, Wang DZ (2012). CIP, a cardiac Isl1-interacting protein, represses cardiomyocyte hypertrophy. Circulation Research. 16;110(6):818-30.
15. Jian-Fu Chen*, Fan Lai, Lee Niswander* (2012). The ubiquitin ligase mLin41 temporally promotes neural progenitor cell maintenance through FGF signaling. Genes & Development. 26(8): 803-15. (Cover, *Co-corresponding author) http://genesdev.cshlp.org/content/26/8/803.long
16. Harmacek L, Watkins-Chow DE, Chen J, Jones KL, Pavan WJ, Salbaum JM, Niswander L (2013). A unique missense allele of BAF155, a core BAF chromatin remodeling complex protein, causes neural tube closure defects in mice. Developmental Neurobiology. 74(5):483-97.
17. Jian-Fu Chen*, Ying Zhang, Jonathan Wilde, Kirk Hansen, Fan Lai, Lee Niswander*. (2014) Microcephaly disease gene Wdr62 regulates mitotic progression of embryonic neural stem cells and brain size. Nature Communication. May 30;5:3885. (*Co-corresponding author) http://www.nature.com/ncomms/2014/140530/ncomms4885/full/ncomms4885.html
18. Mei Yang, Si-Lu Yang, Stephanie Herrlinger, Chen Liang, Monika Dzieciatkowska, Kirk C. Hansen, Ridham Desai, Andras Nagy, Lee Niswander, Eric Moss, Jian-Fu Chen. (2015) Lin28 promotes proliferative capacity of neural progenitor cells in brain development. Development. May 1:142(9):1616-27.
19. Si-Lu Yang, Mei Yang, Stephanie Herrlinger, Chen Liang, Fan Lai, Jian-Fu Chen (2015) MiR-302/367 regulate neural progenitor proliferation, differentiation timing, and survival in neurulation. Developmental Biology. 1;408(1):140-50.
Neural progenitor cells (NPCs), neural development, and neural degeneration