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Lai-Chu Wu

Associate Professor

Office: S2077 Davis
Phone: (614) 293-3042


Ph.D. - University of Oxford, Oxford, England
Post Doctoral - MRC Laboratory of Molecular Biology, Cambridge, England

Our research started as a curiosity to understand the mechanism of somatic V(D)J recombination. The variable regions of the immunoglobulin and T cell receptor genes are not encoded in our genome but are assembled by V(D)J recombination during B and T cell development, respectively. V(D)J recombination is a site specific somatic DNA rearrangement event mediated by the recombination signal sequences (RSS) and products of recombination activating genes (RAG1 and RAG2). Given that RAG1 and RAG2 are present in all developing lymphocytes capable of V(D)J recombination, it is still puzzling what controls the selection and ordering of recombination of specific gene segments. We have identified a large zinc finger protein KRC/ZAS3 that binds to the RSS as well as to the kappa B enhancer motif.; Because ZAS3 is an unusually large DNA binding protein with many structural domains and motifs, we propose that it may provide a platform for the interaction of the recombination and transcription machineries, and hence contributes to the regulation of V(D)J recombination. Of interest, ZAS3 is not only the major RSS binding protein present in lymphocytes, its DNA binding ability is subjected to feedback regulation of V(D)J recombination. Besides serving as a transcription factor for genes involved in growth and metastasis, ZAS3 has recently been shown to inhibit NF-kappaB signaling through specific interaction with the TNF receptor associated factors. Other properties, such as its gene structure and regulation of gene expression, make the study of ZAS3 a challenge. For example, one intriguing finding was that one of the ZAS3 intron, when retained in mRNA, encodes for a DNA binding structure. The study of ZAS3 and its related genes may provide footprints to trace the evolution of the vertebrate genomes.

Recent Publications:

  • Shin DH, Park KW, Wu LC and Hong JW (2011) "ZAS3 promotes TNFα-induced apoptosis by blocking NF?B-activated expression of the anti-apoptotic genes TRAF1 and TRAF2" BMB Rep. 2011 Apr;44(4):267-72.
  • Wu LC, Pfeiffer DR, Calhoon EA, Madiai F, Marcucci G, Liu S and Jurkowitz MS (2011) "Purification, identification, and cloning of lysoplasmalogenase, the enzyme that catalyzes hydrolysis of the vinyl ether bond of lysoplasmalogen" J Biol Chem. Apr 22. [Epub ahead of print]
  • Nam J, Perera P, Liu J, Wu LC, Rath B, Butterfield TA and Agarwal S (2011) "Transcriptome-wide gene regulation by gentle treadmill walking during the progression of monoiodoacetate induced arthritis" Arthritis Rheum.  Mar 11. doi: 10.1002/art.30311. [Epub ahead of print]
  • Liu S, Madiai F, Hackshaw KV, Allen CE, Carl J, Huschart E, Karanfilov C, Litsky A, Hickey CJ, Marcucci G, Huja S, Agarwal S, Yu J, Caligiuri MA and Wu LC (2011) "The large zinc finger protein ZAS3 is a critical modulator of osteoclastogenesis" PLoS One. 6(3):e17161.
  • Yakovich AJ, Jiang B, Allen CE, Du J, Wu LC and Barnard JA (2011) "ZAS3 accentuates transforming growth factor β signaling in epithelial cells" Cell Signal. 23(1):105-13.
  • Hong JW and Wu LC (2010) "ZAS3 represses NFκB-dependent transcription by direct competition for DNA binding" BMB Rep. 43(12):807-12.
  • Liu JQ, Joshi PS, Wang C, El-Omrani HY, Xiao Y, Liu X, Hagan JP, Liu CG, Wu LC and Bai XF (2010) "Targeting Activation-Induced Cytidine Deaminase Overcome Tumor Evasion of Immunotherapy by CTLs" J Immunol. 184(10):5435-43.
  • Liu S, Wu LC, Pang J, Santhanam R, Schwind S, Wu YZ, Hickey CJ, Yu J, Becker H, Maharry K, Radmacher MD, Li C, Whitman SP, Mishra A, Stauffer N, Eiring AM, Briesewitz R, Baiocchi RA, Chan KK, Paschka P, Caligiuri MA, Byrd JC, Croce CM, Bloomfield CD, Perrotti D, Garzon R and Marcucci G (2010) "Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia." Cancer Cell. 17(4):333-47.
  • Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N, Havelange V, Volinia S, Blum W, Rush LJ, Perrotti D, Andreeff M, Bloomfield CD, Byrd JC, Chan K, Wu LC, Croce CM and Marcucci G (2009) "MicroRNA -29b induces global DNA hypomethylation and tumor suppressor gene re-expression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1" Blood 113(25):6411-8.
  • Liu Z, Liu S, Xie Z, Pavlovicz RE, Wu J, Chen P, Aimiuwu J, Pang J, Bhasin D, Neviani P, Fuchs JR, Plass C, Li PK, Li C, Huang TH, Wu LC, Rush L, Wang H, Perrotti D, Marcucci G, Chan KK (2009) "Modulation of DNA Methylation by a Sesquiterpene Lactone Parthenolide" J Pharmacol Exp Ther 329(2):505-14.
  • Liu S, Liu Z, Xie Z, Pang J, Yu J, Lehmann E, Huynh L, Vukosavljevic T, Takeki M, Klisovic RB, Baiocchi RA, Blum W, Porcu P, Garzon R, Byrd JC,Perrotti D, Caligiuri MA, Chan KK, Wu Lc and Marcucci G (2008) "Bortezomib induces DNA hypomethylation and silenced gene transcription by interfering with Sp1/NF-kappaB-dependent DNA methyltransferase activity in acute myeloid leukemia" Blood 111(4):2364-73.
  • Allen CE, Richards J, Muthusamy N, Auer H, Liu Y, Robinson ML, Barnard JA and Wu LC (2007) "Disruption of ZAS3 in mice alters NF-kappaB and AP-1 DNA binding and T-cell development" Gene Expr 14(2):83-100.
  • Yu J, Wei M, Boyd Z, Lehmann EB, Trotta R, Mao H, Liu S, Becknell B, Jaung MS, Jarjoura D, Marcucci G, Wu LC and Caligiuri MA (2007) “Transcriptional control of human T-BET expression: the role of Sp1.” Eur J Immunol. 37(9):2549-61.
  • Wu LC, Goettl VM, Madiai F, Hackshaw KV and Hussain S-R A (2006) "Reciprocal Regulation of Nuclear Factor kappaB and its Inhibitor ZAS3 After Peripheral Nerve Injury" BMC Neuroscience 7:4.
  • Hong JW and Wu LC (2004) "Structural characterization of the gene encoding the large zinc finger protein ZAS3: implication to the origin of multiple promoters in eukaryotic genes" BBA 1681(2-3):74-87.
  • Hong JW, Allen CE and Wu LC (2003) "Inhibition of NF-kappaB by ZAS3, a zinc-finger protein that also binds to the kappaB motif" Proc Natl Acad Sci U S A 100(21):12301-6.
  • Allen C, Mak CH and Wu LC (2002) "The kB transcriptional enhancer motif and signal sequences of V(D)J recombination are targets for the zinc finger protein HIVEP3/KRC: a site selection amplification binding study" BMC Immunology 3:10.
  • Allen CE, Muthusamy R, Wesibrode S and Wu LC (2002) "Developmental anomalies and neoplasia in animals and cells deficient in the large zinc finger protein KRC" Gene Chromosome Canc 35:287-98.