个人简介

Ph.D. (Doctor of Philosophy)

研究领域

Molecular and Development Genetics

Research in the lab centers around two main themes: Function of spermatid-specific proteins in sperm motility and fertilization Function of Odf2 and ciliary proteins in primary cilium elongation. Spermatogenesis represents one of the few ongoing differentiation systems for study in mammals. One problem in the study of spermatogenesis is that it cannot (yet) be recapitulated in cell culture and it is thus difficult to address functional questions: however, transgenic and knockout models are commonly used. Sperm tail studies: We cloned the spermatid-specific Odf1 gene, which encodes a 27 kD sperm tail-specific protein that is a major structural component of outer dense fibers. The function of these fibers, which surround the axoneme in the tail, is unknown. However, we and others provided evidence that in additional to a structural function outer dense fibers may also be involved in regulation of motility. We study Odf1’s interaction with other proteins and its function in the sperm tail. We cloned several proteins that bind Odf1 using yeast 2-hybrid approaches: Odf2, a major ODF protein, Spag4, an axonemal, microtubule-binding protein, Spag5, related to the spindle protein Deepest, and KLC3, a novel kinesin light chain. KLC3 is most likely involved in the dramatic movement of mitochondria from the periphery of haploid spermatids to the midpiece of the sperm tail, a region involved in generating energy for movement. We found that interactions are mediated by leucine zipper motifs. The role of these proteins in morphogenesis and sperm function is a major focus. We have generated Odf2-knockout mice to understand the roles of Odf2 in the sperm tail and in early embryonic development. Primary cilium studies: Primary cilia are present on many cells and appear to function in part as sensory organelle. Primary cilia originate from basal bodies. Abnormalities of primary cilia in human have been linked to serious disease. Recently, it was shown that the spermatid protein Odf2 is a component of centrioles/basal bodies in all somatic cells. Odf2 is crucial for development of the primary cilium. We discovered recently that treatment of cells with lithium (a drug commonly used to treat bipolar disorder) results in dramatic elongation of primary cilia. We study the molecular mechanisms involved in formation and elongation of primary cilia.

近期论文

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Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration.Ou Y, Chan G, Zuo J, Rattner JB, van der Hoorn FA.J Biol Chem. 2016 Jul 15;291(29):15388-403. Primary cilia in the developing pig testis.Ou Y, Dores C, Rodriguez-Sosa JR, van der Hoorn FA, Dobrinski I.Cell Tissue Res. 2014 Nov;358(2):597-605. Sperm-associated antigen 4, a novel hypoxia-inducible factor 1 target, regulates cytokinesis, and its expression correlates with the prognosis of renal cell carcinoma.Shoji K, Murayama T, Mimura I, Wada T, Kume H, Goto A, Ohse T, Tanaka T, Inagi R, van der Hoorn FA, Manabe I, Homma Y, Fukayama M, Sakurai T, Hasegawa T, Aburatani H, Kodama T, Nangaku M.Am J Pathol. 2013 Jun;182(6):2191-203. Targeting of CRMP-2 to the primary cilium is modulated by GSK-3β.Ou Y, Zhang Y, Cheng M, Rattner JB, Dobrinski I, van der Hoorn FA.PLoS One. 2012;7(11):e48773. KLC3 is involved in sperm tail midpiece formation and sperm function.Zhang Y, Ou Y, Cheng M, Saadi HS, Thundathil JC, van der Hoorn FA.Dev Biol. 2012 Jun 15;366(2):101-10. Involvement of classical bipartite/karyopherin nuclear import pathway components in acrosomal trafficking and assembly during bovine and murid spermiogenesis.Tran MH, Aul RB, Xu W, van der Hoorn FA, Oko R.Biol Reprod. 2012 Mar 22;86(3):84. Ornithine decarboxylase antizyme Oaz3 modulates protein phosphatase activity.Ruan Y, Cheng M, Ou Y, Oko R, van der Hoorn FA.J Biol Chem. 2011 Aug 19;286(33):29417-27. Binding of nickel to testicular glutamate-ammonia ligase inhibits its enzymatic activity.Sun Y, Ou Y, Cheng M, Ruan Y, van der Hoorn FA.Mol Reprod Dev. 2011 Feb;78(2):104-15. Gene trap mutation of murine outer dense fiber protein-2 gene can result in sperm tail abnormalities in mice with high percentage chimaerism.Tarnasky H, Cheng M, Ou Y, Thundathil JC, Oko R, van der Hoorn FA.BMC Dev Biol. 2010 Jun 15;10:67. Primary cilia in fibroblast-like type B synoviocytes lie within a cilium pit: a site of endocytosis.Rattner JB, Sciore P, Ou Y, van der Hoorn FA, Lo IK.Histol Histopathol. 2010 Jul;25(7):865-75. Inhibition of tyrosine phosphorylation of sperm flagellar proteins, outer dense fiber protein-2 and tektin-2, is associated with impaired motility during capacitation of hamster spermatozoa.Mariappa D, Aladakatti RH, Dasari SK, Sreekumar A, Wolkowicz M, van der Hoorn F, Seshagiri PB.Mol Reprod Dev. 2010 Feb;77(2):182-93. Na+/K+ATPase regulates sperm capacitation through a mechanism involving kinases and redistribution of its testis-specific isoform.Newton LD, Krishnakumar S, Menon AG, Kastelic JP, van der Hoorn FA, Thundathil JC.Mol Reprod Dev. 2010 Feb;77(2):136-48. Adenylate cyclase regulates elongation of mammalian primary cilia.Ou Y, Ruan Y, Cheng M, Moser JJ, Rattner JB, van der Hoorn FA.Exp Cell Res. 2009 Oct 1;315(16):2802-17. Elevated testicular temperature modulates expression patterns of sperm proteins in Holstein bulls.Newton LD, Kastelic JP, Wong B, van der Hoorn F, Thundathil J.Mol Reprod Dev. 2009 Jan;76(1):109-18. A novel group of multi-GAP-domain proteins.Ruan Y, Sensen CW, van der Hoorn FA.Mol Reprod Dev. 2008 Oct;75(10):1578-89. ODF1 phosphorylation by Cdk5/p35 enhances ODF1-OIP1 interaction.Rosales JL, Sarker K, Ho N, Broniewska M, Wong P, Cheng M, van der Hoorn FA, Lee KY.Cell Physiol Biochem. 2007;20(5):311-8. The anatomy of the cerebellar nuclei in the normal and scrambler mouse as revealed by the expression of the microtubule-associated protein kinesin light chain 3.Chung S, Zhang Y, Van Der Hoorn F, Hawkes R.Brain Res. 2007 Apr 6;1140:120-31. Mammalian transcription in support of hybrid mRNA and protein synthesis in testis and lung.Fitzgerald C, Sikora C, Lawson V, Dong K, Cheng M, Oko R, van der Hoorn FA.J Biol Chem. 2006 Dec 15;281(50):38172-80. Rat Spag5 associates in somatic cells with endoplasmic reticulum and microtubules but in spermatozoa with outer dense fibers.Fitzgerald CJ, Oko RJ, van der Hoorn FA.Mol Reprod Dev. 2006 Jan;73(1):92-100. Rat kinesin light chain 3 associates with spermatid mitochondria.Zhang Y, Oko R, van der Hoorn FA.Dev Biol. 2004 Nov 1;275(1):23-33.