Moe Mahjoub, Ph.D.

Assistant Professor
Internal Medicine
Renal

Molecular Cell Biology Program
Developmental, Regenerative and Stem Cell Biology Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-362-5681

  • 314-454-5126

  • 8126

  • Wohl Clinic Bldg, Rm 8830C

  • mmahjoub@dom.wustl.edu

  • http://mahjoublab.wustl.edu

  • Cilia, centrosome, cell division, signal transduction, cell differentiation, kidney development

  • Molecular mechanisms of centrosome biogenesis and ciliogenesis, and their roles in development and disease

Research Abstract:

The focus of research in our laboratory is to understand how two essential organelles, the centrosome and cilium, organize signaling pathways that control diverse cellular functions. These highly conserved organelles act as signaling hubs that regulate various aspects of cell-cycle progression, cell differentiation, polarity, and migration. At the core of the centrosome is a pair of microtubule-based structures called centrioles, which are surrounded by an amorphous mix of proteins called the pericentriolar matrix. Centrioles play a critical role in cells by serving as basal bodies that nucleate the formation of the primary cilium. Except for a few specialized cell types, almost every cell in the human body contains a primary cilium. Defects in the structure and function of centrosomes and cilia lead to a range of human disease phenotypes known collectively as "Ciliopathies". These include developmental defects such as polycystic kidney disease, nephronophthisis, polydactyly, infertility, hydrocephalus and cancer, as well as neurocognitive defects including mental retardation and dyslexia.

We employ genomic, proteomic, biochemical and cell biological methods to delineate the regulation of centrosome-cilium assembly and function. We have recently identified a set of proteins involved in the assembly and maturation of centrioles. We also determined the consequences of defects in the regulation of this protein complex, which leads to defective ciliary signaling causing abnormal cell division, polarity and migration. Current experiments are focused on (1) determining the molecular mechanisms of protein trafficking and localization to cilia; (2) proteomic approaches to identify regulatory proteins involved in centriole assembly and duplication; (3) examining the consequences of abnormal centrosome and cilium function in human disease, with particular emphasis on ciliopathies affecting the kidney, such as polycystic kidney disease, nephronophthisis and cancer.

For a more detailed description of our research visit http://mahjoublab.wustl.edu

Selected Publications:

Potter C, Zhu W, Razafsky D, Ruzycki P, Kolesnikov AV, Doggett T, Kefalov VJ, Betleja E, Mahjoub MR and Hodzic D. (2017). Multiple isoforms of Nesprin1 are integral components of ciliary rootlets. Current Biology. 10;27(13):2014-2022.

Hwang VJ, Zhou X, Chen X, Trott J, Abu Aboud O, Shim K, Dionne LK, Senapedis W, Baloglu E, Mahjoub MR, Li X, and Weiss RH (2017). Anti-cystogenic activity of a small molecule PAK4 inhibitor as a novel treatment for ADPKD. Kidney International. 92(4):922-933.

Silva E, Betleja E, John E, Spear P, Moresco JJ, Zhang S, Yates JR 3rd, Mitchell BJ, Mahjoub MR. (2016). Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left-right asymmetry. Mol Biol Cell. 1;27(1):48-63.

Hoshi M, Wang J, Jain S and Mahjoub MR. (2015). Imaging centrosomes and cilia in the mouse kidney. Methods in Cell Biology. 127:1-17.

Mahjoub MR and Tsou MFB. (2013). The amAZI1ng roles of centriolar satellites during development. PLOS Genetics. 9(12): e1004070.

Mahjoub MR. (2013). The importance of a single primary cilium. Organogenesis. 9(2) 0-8.

Mahjoub MR and Stearns T. (2012). Supernumerary centrosomes nucleate extra cilia and compromise primary cilium signaling. Current Biology, 22(17):1628-34.

Park KS, Martelotto LG, Peifer M, Sos ML, Karnezis AN, Mahjoub MR, Bernard K, Conklin J, Szczepny A, Yuan J, Guo R, Ospina B, Falzon J, Bennett S, Brown TJ, Markovic A, Devereux WL, Ocasio CA, Chen JK, Stearns T, Thomas RK, Dorsch M, Buonamici S, Watkins DN, Peacock CD and Sage J. (2011). A crucial requirement for Hedgehog signaling in small cell lung cancer. Nature Medicine, 17(11):1504-8.

Mahjoub MR, Xie Z and Stearns T. (2010). Cep120 is asymmetrically localized to the daughter centriole and is essential for centriole assembly. J Cell Biol. 191(2):331-46.

Parker JD, Hilton LK, Diener DR, Rasi MQ, Mahjoub MR, Rosenbaum JL and Quarmby LM. (2010). Centrioles are freed from cilia by severing prior to mitosis. Cytoskeleton 67(7):425-30.

Mahjoub MR, Trapp ML and Quarmby LM. (2005). NIMA-related kinases defective in murine models of polycystic kidney diseases localize to primary cilia and centrosomes. J. Am. Soc. Nephrol. 16(12): 3485-3489.

Quarmby LM and Mahjoub MR (2005). Caught Nek-ing: Cilia and centrioles. J Cell Sci 118: 5161-5169.

Mahjoub MR, Rasi QM and Quarmby LM (2004). A NIMA-related kinase, Fa2p, localizes to a novel site in the proximal cilia of Chlamydomonas and mouse kidney cells. Mol Biol Cell. 15(11):5172-86.

Blacque OE, Reardon MJ, Li C, McCarthy J, Mahjoub MR, Ansley SJ, Badano JL, Mah AK, Beales PL, Davidson WS, Johnsen RC, Audeh M, Plasterk RH, Baillie DL, Katsanis N, Quarmby LM, Wicks SR and Leroux MR (2004). Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport. Genes Dev. 18: 1630-42.

Mahjoub MR, Montpetit B, Zhao L, Finst RJ, Goh B, Kim AC and Quarmby LM (2002). The FA2 gene of Chlamydomonas encodes a NIMA family kinase with roles in cell cycle progression and microtubule severing during deflagellation. J. Cell Sci. 115, 1759-1768.

Last Updated: 1/2/2018 12:02:27 PM

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