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    Centrosome Regulation in Development and Disease

     

    Centrosome | RNA biology | Drosophila

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    Research Interests 

     

     

    Centrosomes are microtubule-organizing centers with diverse functions directing cell division, cell polarization, and cilia formation. The deregulation of centrosomes is associated with developmental disorders, including microcephaly, dwarfism, and ciliopathy. Using multi-disciplinary approaches, we investigate how diverse centrosome function is precisely regulated. We aim to inform mechanisms underlying centrosome regulation and reveal the etiology of centrosome-associated neurodevelopmental diseases.

     

    We are particularly interested in the following directions:

    1. Recent research uncovers centrosome regulation at the mRNA level. We will investigate how mRNA regulation, mediated by various RNA binding proteins (RBPs), contributes to diverse centrosome functions.
    2. Most centrosomal genes encode multiple mRNA isoforms, an essential mechanism that diversifies gene products. Using essential centrosome genes as models, we will investigate how isoform expression contributes to diverse centrosome functions.
    3. Recent studies show that neurodevelopmental disease-relevant RBPs co-exist in the centrosome interactome in human neural stem cells (NSCs) and neurons. We will investigate how centrosome deregulation contributes to neurodevelopmental diseases.

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    Centrosome structure and function

    Functioning as microtubule-organizing centers (MTOC) in most animal cells, centrosomes are composed of a pair of centrioles surrounded by pericentriolar material (PCM). The centrosome is a multi-functional organelle, that directs the formation of mitotic spindles in dividing cells to ensure error-free mitosis, contributes to cell polarity, directs cilia formation, and organizes organelles and traffic intracellular cargo. The deregulation of centrosomes can lead to developmental disorders, including, cancer, microcephaly, and ciliopathy.

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    Regulation of centrosome-associated mRNA

    RNA was known to distribute at centrosomes in diverse cell types for decades, indicating that centrosome activity is regulated at the mRNA level. Yet the types of RNA, the underlying localization mechanisms, and their functional roles are largely unknown. Using single-molecule fluorescence in situ hybridization (smFISH), my recent postdoctoral research shows that mRNA encoded by several centrosome-related genes localizes at centrosomes. In addition, using two mRNA: Cen and Plp mRNA as models, we uncover a novel mechanism of centrosome activity controlled by diverse RNA binding proteins, through regulating mRNA localization, mRNA translation, or mRNA polyadenylation (Fang and Lerit, 2022; #Ryder, #Fang, et al., 2020).

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    Differential mRNA isoform expression & function

    Isoform expression is an essential mechanism that diversifies gene products. Most centrosome-related genes encode multiple isoforms. Aberrant isoform expression has gained emerging attention in contributing to human diseases. Yet, how isoform expression dictates diverse centrosome structure/function remains a significant knowledge gap. The Fang lab will employ key centrosome-related genes as models to investigate how isoform expression contributes to centrosome heterogeneity across diverse cell types. (This project is currently supported by an NIGMS K99/R00 award).

     

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    Publications

    A full list of publications can be found at Bibliography

    • Fang, J.#, Tian, R.#, Quintanilla, M.,Beach, J., Lerit, D.A. The PCM scaffold enables RNA localization to centrosomes. bioRxiv:           
    • #Equal contributors.     

    • Brockett, J.S., Manalo, T., Zein-Sabatto, H.,Lee, J., Fang, J., Chu, P., Feng, H., Patil, D., Davidson, P., Ogan, K., Master, V.A.,Pattaras, J.G., Roberts, D.L., Bergquist, S.H., Reyna, M. A., Petros, J.A., Lerit, D.A., Arnold, R.S. A missense SNP in the tumor suppressor SETD2 reduces H3K36me3 and mitotic spindle integrity in Drosophila. Genetics. 2024 Apr; 226 (4). PMID:38290049.

    • Fang, J., Lerit, D.A. Orb-dependent polyadenylation contributes to PLP expression and centrosome scaffold assembly. Development. 2022 Jul 1;149(13). PMID: 35661190.
    • Featured Cover Article. July 2022 Issue.

    • #Ryder, P., #Fang, J.,Lerit, D.A. centrocortin RNA localization to centrosomes is regulated by FMRP and facilitateserror-free mitosis. J. Cell. Biol. 2020 Dec 7; 219(12). PMID: 33196763.
    • #Equal contributors.

    • Fang, J., Lerit, D.A. (2020) DrosophilaPericentrin-like protein promotes the formation of primordial germ cells. Genesis. 2020 Mar; 58(3-4):e23347. PMID:31774613.
    • Featured Cover Article. March-April 2020 Issue.
       

    • Fang, J., Jing, X., Lu, G., Jing, X., Xu, Y., Gong P. (2019) Crystallographic snapshots of the Zika virus NS3helicase helps visualize the reactant water replenishment. ACS Infect Dis. Feb 8;5(2):177-183. PMID: 30672289.

    • Benner, L., Castro, E.A., Whitworth, C.,Venken, K.J.T., Yang, H., Fang, J., Oliver, B., Cook, K.R., and Lerit,D.A. (2019) Drosophila Heterochromatin stabilization requires the zinc-finger proteinSmall Ovary. Genetics. 2019 Nov;213(3):877-895. PMID: 31558581.

    • Fang, Q., Chen, P., Wang, M., Fang, J., Yang, N., Li, G., Xu,RM. (2016) Human cytomegalovirus IE1protein alters the higher-order chromatin structure by targeting the acidic patch of thenucleosome. eLife. Jan 26e11911. PMID: 26812545.

    • Fang, J., Liu, Y., Wei, Y., Deng, W., Yu, Z., Huang, L., Teng, Y., Yao, T., You, Q., Ruan, H., Chen, P., Xu, RM.,Li, G. (2015) Structural Transitions of Centromeric Chromatin Coordinate the CellCycle-dependent Recruitment of CENP-N. Genes& Development. 29 (10):1058-73. PMID: 25943375.

    • Yu, Z., Zhou, X., Wang, W., Deng, W., Fang, J., Hu, H., Wang Z., Li,S., Cui, L., Shen, J., Zhai, L., Peng, S.,Wong, J., Dong, S., Yuan, Z., Ou, G., Zhang, X., Xu, P., Lou, J., Yang, N., Chen, P., Xu, RM.,Li, G. (2015) Dynamic phosphorylation of Ser68 orchestrates the cellcycle-dependent deposition of CENP-A at centromeres. Developmental Cell. 32: 68-81. PMID:25556658.

  • We are hiring at all levels!

    NIH-funded Postdoctoral positions and Research Specialist positions are available. 

    Interested applicants are encouraged to directly email Dr. Fang (fang.1142@osu.edu) with the following documents: a brief statement of research interest, an updated CV, and contact details of three references.

    PhD applications: apply via the link here. 

    Training opportunities

    In the Fang lab, you'll have the exciting opportunities to publish in prestigious journals, draft and submit your grants, present your research at international conferences, and receive formal & tailored career development training.

    Collaborations/Teamwork

    We place a strong emphasis on collaboration and teamwork.

    Leadership roles, expectations, and contributions will be discussed with all team members at the start of each project, with periodic reviews as the project progresses. Effective communication is essential to our success.

    Work/Life Balance

    Science is both rewarding and challenging. Maintaining a healthy work-life balance is essential for preserving enthusiasm and productivity. We encourage a balanced approach that allows for dedicated time to both scientific work and personal interests.

     

    Resources for learning about life in Columbus: link here.

    Commitment to Inclusion

    The Fang lab welcomes students/scholars interested in bioinformatics, genetics, cell biology, RNA biology, and centrosomes regardless of their background.

    We are committed to fostering a supportive and inclusive environment within the laboratory and across the broader academic community.

  •  Lab Members

    Welcome to the Fang lab!

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    Junnan Fang, Ph.D. Principle Investigator

    Assistant Professor of Physiology and Cell Biology

    email: fang.1142@osu.edu

    Dr. Junnan Fang received her Ph.D. in Biochemistry and Molecular Biology from the Institute of Biophysics, Chinese Academy of Sciences. She is currently a postdoctoral fellow at Emory University. Beginning in January 2025, Dr. Fang will join The Ohio State University as an Assistant Professor on a tenure-track appointment.
    Dr. Fang is a recipient of the NIH/NIGMS K99/R00 Pathway to Independence Award.
    In her leisure time, she enjoys reading, hiking, and traveling.

  • Contact

    You are welcome to reach out. You + us = awesome.

    Graves Hall, 333 W 10th Ave, Columbus, OH 43210
    fang.1142@osu.edu

  • Lab News

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    The FANG LAB @ OSU will be open soon in January 2025.

    More lab news is coming soon.

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    2024.09

    Junnan served on the Mentoring & Diversity Career Panel for the Marion Hines Lecture hosted by the Dept. of Cell Biology at Emory

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