2015.9-至今：中國(guó)科學(xué)院生物與化學(xué)交叉研究中心，研究員、課題組長(zhǎng)
2015-2015：普羅簡(jiǎn)那有限公司，研究員
2013-2015：耶魯大學(xué)醫(yī)學(xué)院，副研究科學(xué)家
2009-2012：美國(guó)國(guó)立衛(wèi)生研究院，博士后
2004-2009：中國(guó)科學(xué)院生物物理研究所，生物化學(xué)博士
2000-2004：山東大學(xué)生命科學(xué)學(xué)院，學(xué)士
主要研究細(xì)胞內(nèi)蛋白質(zhì)降解（protein degradation）的各種機(jī)制、以及內(nèi)質(zhì)網(wǎng)維持其蛋白質(zhì)及膜組分穩(wěn)態(tài)平衡的分子機(jī)理。目標(biāo)是理解有錯(cuò)誤折疊傾向的蛋白在細(xì)胞內(nèi)沉積的機(jī)制，了解它們?yōu)楹纬掷m(xù)存留在老化的細(xì)胞內(nèi)，并且發(fā)展出有效的策略來(lái)減輕錯(cuò)誤折疊蛋白對(duì)細(xì)胞或機(jī)體組織造成的負(fù)擔(dān)或損傷。我們將綜合應(yīng)用生物化學(xué)、細(xì)胞生物學(xué)、生物物理學(xué)，并結(jié)合蛋白質(zhì)組學(xué)和高分辨率成像等技術(shù)，研究以下基本問題：?
1. 錯(cuò)誤折疊的跨膜蛋白被質(zhì)量控制系統(tǒng)識(shí)別(recognition)、分選(triage)、泛素化修飾 (ubiquitination)、并傳遞到蛋白酶體(proteasome)或溶酶體(lysosome)進(jìn)行降解 (degradation)的分子機(jī)制。?
2. 內(nèi)質(zhì)網(wǎng)與細(xì)胞核進(jìn)行有效的信息交流從而使細(xì)胞能夠?qū)沟鞍踪|(zhì)錯(cuò)誤折疊或聚集的分子機(jī)制。?
3. O-聯(lián)接糖基化 (O-GlcNAc glycosylation) 等翻譯后修飾方式對(duì)內(nèi)質(zhì)網(wǎng)蛋白質(zhì)穩(wěn)態(tài)的調(diào)控機(jī)制及其與機(jī)體壽命的關(guān)系。?
1. Plumb R*, Zhang ZR*, Appathurai S, &Mariappan M. (2015) A functional link between the co-translational protein translocation pathway and the UPR. eLife 4: e07426 (*Co-first authors)
2. Park SY, Waheed AA, Zhang ZR, Freed EO, & Bonifacino JS.(2014) HIV-1 Vpu accessory protein induces caspase-mediated cleavage of IRF3 transcription factor.J. Biol. Chem. 289, 35102-35110
3. Zhang ZR*, Bonifacino JS, &Hegde RS*. (2013) Deubiquitinases Sharpen Substrate Discrimination during Membrane Protein Degradation from the ER. Cell 154, 609-622 (* Co-corresponding authors)
4. Moran C, Kinsella GK, Zhang ZR, Perrett S, & Jones GW. (2013) Mutational Analysis of Sse1 (Hsp110) Suggests an Integral Role for this Chaperone in Yeast Prion Propagation In Vivo. G3: Genes, Genomes, Genetics 3, 1409-1418
5. Emerman AB, Zhang ZR,Chakrabarti O, &Hegde RS. (2010). Compartment-restricted biotinylation reveals novel features of prion protein metabolism in vivo. Mol. Biol. Cell 21, 4325-4337
6. Zhang C, Jackson A, Zhang ZR, Han Y, Yu S, He RQ, and Perrett S. (2010). Amyloid-Like aggregates of the yeast prion protein Ure2 enter vertebrate cells by specific endocytotic pathways and induce apoptosis. PLoS One 5, e12529
7. Zhang ZR, and Perrett S. (2009). Novel glutaredoxin activity of the yeast prion protein Ure2 reveals a native-like dimer within fibrils. J. Biol. Chem.284, 14058-14067
8. Wang XY, Zhang ZR, and Perrett S. (2009). Characterization of the activity and folding of the glutathione transferase from Escherichia coli and the roles of residues Cys10 and His106. Biochem. J.417, 55-64
9. Zhang ZR, Bai M, Wang XY, Zhou JM & Perrett S. (2008). "Restoration" of glutathione transferase activity by single-site mutation of the yeast prion protein Ure2. J. Mol. Biol. 384, 641-651
10. Lian HY, Zhang H, Zhang ZR, Loovers HM, Jones GW, Rowling PJ, Itzhaki LS, Zhou JM & Perrett S. (2007). Hsp40 interacts directly with the native state of the yeast prion protein Ure2 and inhibits formation of amyloid-like fibrils. J. Biol. Chem. 282, 11931-11940
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