Introduction
 Post-translational modifications of ubiquitin and ubiquitin-like proteins (Ubls) control myriad of cellular processes ranging from cell cycle regulation, transcription and DNA repair to virus budding. Ubls are attached to protein targets by a hierarchical cascade of enzymes involving an E1 activating enzyme, an E2 conjugating enzyme, and an E3 ligase.
Defects in these pathways have been associated with diseases such as cancer, neurodegenerative disorder and viral infection. Bortezomib (Velcade) targets ubiquitin-proteasome system, is presently approved for treating multiple myeloma demonstrating the importance of the ubiquitin-proteasome pathway in anti-cancer therapies.
Our group is interested in understanding the molecular mechanism histone ubiquitination and the functional roles of ubiquitin in transcription regulation. We will apply X-ray crystallography and biochemical assays to study various histone ubiquitinases to dissect their functions, substrates recognition, and interaction with other molecular factors.
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Lab Report
 Scientific Report 2010 Huang (181.4 kB)
Key PublicationsDou H, Buetow L, Hock A, Sibbet GJ, Vousden KH, Huang DT. Structural basis for autoinhibition and phosphorylation-dependent activation of c-Cbl. Nature Strucutral & Molecular Biology doi:10.1038/nsmb.2231, publsihed online 22 Jan 2012.
Huang DT, Ayrault O, Hunt HW, Taherbhoy AT, Duda DM, Scott DC, Borg LA, Neale G, Murray PJ, Roussel MF, Schulman BA (2009). E2-RING expansion of the NEDD8 cascade confers specificity to Cullin modification. Molecular Cell 33, 483-95.
Huang DT, Zhuang M, Schulman BA (2008). Identification of conjugation specificity determinants unmasks vestigial preference for ubiquitin within the NEDD8 E2. Nature Structural Mol Biol. 15, 280-7.
Huang DT, Hunt HW, Zhuang M, Ohi MD, Holton JM, Schulman BA (2007). Basis for a ubiquitin-like protein thioester switch toggling E1–E2 affinity. Nature 445, 394-8.
Huang DT, Schulman BA (2006). Breaking up with a kinky SUMO. Nature Structural Mol Biol. 13, 1045-7.
Biography
Education and qualifications
2002: PhD, University of Sydney, Australia, Supervisor Richard Christopherson
1996: BSc, Biochemistry (First Class Honours), University of Sydney, Australia
Appointments
2009-present: Group Leader, Beatson Institute for Cancer Research
2007-2009: Staff Scientist with Brenda Schulman, St Jude Children’s Research Hospital, USA
2006-2007: Postdoctoral Fellow with Brenda Schulman, HHMI, USA
2002-2005: Postdoctoral Fellow with Brenda Schulman, St Jude Children’s Research Hospital, USA
Honours and awards
Lorne Protein Young Investigator Award, 2006
Recent Publications
2012
Dou H, Buetow L, Hock A, Sibbet GJ, Vousden KH, Huang DT. Structural basis for autoinhibition and phosphorylation-dependent activation of c-Cbl. Nature Strucutral & Molecular Biology doi:10.1038/nsmb.2231, publsihed online 22 Jan 2012.
2010
Wang J, Taherbhoy AM, Hunt HW, Seyedin SN,
Miller DW, Miller DJ, Huang DT,
Schulman BA (2010).
Crystal structure of UBA2ufd-Ubc9: insights into
E1-E2 interactions in Sumo pathways. PLoS ONE 5, e15805.
2009
Huang DT, Ayrault O, Hunt HW, Taherbhoy AT, Duda DM, Scott DC, Borg LA, Neale G, Murray PJ, Roussel MF, Schulman BA (2009). E2-RING expansion of the NEDD8 cascade confers specificity to Cullin modification. Molecular Cell 33, 483-95.
2008
Huang DT, Zhuang M, Schulman BA (2008). Identification of conjugation specificity determinants unmasks vestigial preference for ubiquitin within the NEDD8 E2. Nature Structural Mol Biol. 15, 280-7.
2007
Huang DT, Hunt HW, Zhuang M, Ohi MD, Holton JM, Schulman BA (2007). Basis for a ubiquitin-like protein thioester switch toggling E1–E2 affinity. Nature 445, 394-8.
2006
Huang DT, Schulman BA (2006). Breaking up with a kinky SUMO. Nature Structural Mol Biol. 13, 1045-7.
Huang DT, Kaplan J, Menz RI, Katis VL, Wake RG, Zhao F, Wolfenden R, Christopherson RI (2006). Thermodynamic analysis of catalysis by the dihydroorotases from hamster and Bacillus caldolyticus, as compared with the uncatalyzed reaction. Biochem. 45, 8275-83.
Anderson MA, Cleland WW, Huang DT, Chan C, Shojaei M, Christopherson RI (2006). 13C and 15N isotope effects for conversion of L-dihydroorotate to N-carbamyl-L-aspartate using dihydroorotase from hamster and Bacillus caldolyticus. Biochem. 45, 7132-9.
Lab Members
Post-doc: Lori Buetow
Scientific Officer: Gary Sibbet
PhD Students: Hao Dou, Gabriele Marciano
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