Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor composed of a HIF alpha subunit and a beta/ARNT subunit. While HIF beta subunit is constitutively expressed, HIF alpha subunit is rapidly degraded at normoxia by the ubiquitin-proteasome pathway. Importantly, it has been shown recently that the prolyl hydroxylation of HIF alpha subunit is required for its ubiquitination and subsequent destruction. The a subunit becomes hydroxylated by a family of newly identified prolyl-4-hydroxylases. Three prolyl hydroxylases namely EGLN1, 2, 3 have been identified to date.

My research focus is on elucidating of the biochemical and biological roles of SM20, the orthologue of EGLN-3, with a specific emphasis on deciphering the effect of SM20 on the differentiation and development of skeletal muscle. Towards this end, we have been using pharmalogical inhibitors to repress the activity of the prolyl hydroxylase, siRNAs to knock down SM20 expression level, and transient transfection strategy to overexpress SM20 to reveal a role for SM20 in the differentiation of cultured skeletal myoblasts. Strikingly, our preliminary results suggest that SM20 is involved in myogenesis. Our intriguing finding prompts us to dissect the underlying mechanism(s). It has been well documented that the myogenic differentiation is mainly orchestrated by a family of muscle regulatory factors (MRFs) including MyoD, myogenin, Myf-5, and MRF4. As a first step, work is in progress to explore the impact of SM20 on these master muscle-specific molecules. Further efforts will be made to identify more complicated molecular basis of SM20 on myogenesis by employing a broad variety of approaches such as (but not limited to) cDNA microarray and proteomics methodologies. In addition, we set out to create the SM20 knock-out mice to obtain more complex picture of how SM20 regulates myogenesis and development. Our study will improve the understanding of the biochemical and biological relevance of SM20 and provide novel insights into the regulation of myogenic differentiation.

• Fu J, Ivy Yu HM, Maruyama T, Mirando AJ, Hsu W. Gpr177/mouse Wntless is essential for Wnt-mediated craniofacial and brain development. Dev Dyn. 2011 Feb; 240(2):365-71.
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• Mirando AJ, Maruyama T, Fu J, Yu HM, Hsu W. ß-catenin/cyclin D1 mediated development of suture mesenchyme in calvarial morphogenesis. BMC Dev Biol. 2010; 10:116.
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• Yu HM, Jin Y, Fu J, Hsu W. Expression of Gpr177, a Wnt trafficking regulator, in mouse embryogenesis. Dev Dyn. 2010 Jul; 239(7):2102-9.
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• Fu J, Taubman MB. Prolyl hydroxylase EGLN3 regulates skeletal myoblast differentiation through an NF-kappaB-dependent pathway. J Biol Chem. 2010 Mar 19; 285(12):8927-35.
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• Fu J, Jiang M, Mirando AJ, Yu HM, Hsu W. Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic axis formation. Proc Natl Acad Sci U S A. 2009 Nov 3; 106(44):18598-603.
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• Fu J, Menzies K, Freeman RS, Taubman MB. EGLN3 prolyl hydroxylase regulates skeletal muscle differentiation and myogenin protein stability. J Biol Chem. 2007 Apr 27; 282(17):12410-8.
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• Fu J, Jin Y, Arend LJ. Smac3, a novel Smac/DIABLO splicing variant, attenuates the stability and apoptosis-inhibiting activity of X-linked inhibitor of apoptosis protein. J Biol Chem. 2003 Dec 26; 278(52):52660-72.
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• Saunders RH, Davila E, Hayes AL, Fu J, Zero DT. The effectiveness of sponge-type intraoral applicators for applying topical fluorides in institutionalized older adults. Spec Care Dentist. 1994 Nov-Dec; 14(6):224-8.
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• Zero DT, Raubertas RF, Fu J, Pedersen AM, Hayes AL, Featherstone JD. Fluoride concentrations in plaque, whole saliva, and ductal saliva after application of home-use topical fluorides [published eerratum appears in J Dent Res 1993 Jan;72(1):87]. J Dent Res. 1992 Nov; 71(11):1768-75.
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• Zero DT, Raubertas RF, Pedersen AM, Fu J, Hayes AL, Featherstone JD. Studies of fluoride retention by oral soft tissues after the application of home-use topical fluorides. J Dent Res. 1992 Sep; 71(9):1546-52.
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• Zero DT, Fu J, Anne KM, Cassata S, McCormack SM, Gwinner LM. An improved intra-oral enamel demineralization test model for the study of dental caries. J Dent Res. 1992 Apr; 71 Spec No:871-8.
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• Meyerowitz C, Featherstone JD, Billings RJ, Eisenberg AD, Fu J, Shariati M, Zero DT. Use of an intra-oral model to evaluate 0.05% sodium fluoride mouthrinse in radiation-induced hyposalivation. J Dent Res. 1991 May; 70(5):894-8.
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• Zero DT, Rahbek I, Fu J, Proskin HM, Featherstone JD. Comparison of the iodide permeability test, the surface microhardness test, and mineral dissolution of bovine enamel following acid challenge. Caries Res. 1990; 24(3):181-8.
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• Zero DT, Fu J, Espeland MA, Featherstone JD. Comparison of fluoride concentrations in unstimulated whole saliva following the use of a fluoride dentifrice and a fluoride rinse. J Dent Res. 1988 Oct; 67(10):1257-62.
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• Billings RJ, Meyerowitz C, Featherstone JD, Espeland MA, Fu J, Cooper LF, Proskin HM. Retention of topical fluoride in the mouths of xerostomic subjects. Caries Res. 1988; 22(5):306-10.
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• Featherstone JD, Shariati M, Brugler S, Fu J, White DJ. Effect of an anticalculus dentifrice on lesion progression under pH cycling conditions in vitro. Caries Res. 1988; 22(6):337-41.
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