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Ying E. Zhang, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute

RESEARCH SUMMARY

Dr. Zhang's research focuses on understanding TGF-beta signaling and functions of ubiquitin E3 ligase Smurfs. She identified and characterized several key molecules in the TGF-beta signaling pathway, including Smads and Smurfs. Discoveries from her group generated mechanistic insight into how TGF-beta controls cellular responses through Smad-dependent and -independent pathways in normal and cancer cells. On the front of Smurf E3 ligases, their findings extended the function of Smurfs beyond TGF-beta pathway to genome stability and metastasis.

Areas of Expertise

1) signaling transduction, 2) TGF-beta signaling, 3) protein kinases, 4) ubiquitination,
5) mouse models, 6) metastasis

Publications

Selected Key Publications

TGF-β-induced Alternative Splicing of TAK1 Promotes EMT and Drug Resistance

Tripathi V, Shin JH, Stuelten CH, Zhang YE.
Oncogene. 38(17): 3185-3200, 2019. [ Journal Article ]

Mechanistic Insight Into Contextual TGF-β Signaling

Zhang YE.
Curr Opin Cell Biol. 51: 1-7, 2018. [ Journal Article ]

Non-proteolytic ubiquitin modification of PPARγ by Smurf1 protects the liver from steatosis

Zhu K, Tang Y , Xu X , Dang H , Tang LY , Wang X, Wang XW , Zhang YE
PLOS Biology. 16(12): e3000091, 2018. [ Journal Article ]

Transforming Growth Factor-β (TGF-β) Directly Activates the JAK1-STAT3 Axis to Induce Hepatic Fibrosis in Coordination with the SMAD Pathway

Tang LY, Heller M, Meng Z, Yu LR, Tang Y, Zhou M, Zhang YE.
J Biol Chem. 292(10): 4302-12, 2017. [ Journal Article ]

Direct Regulation of Alternative Splicing by SMAD3 through PCBP1 Is Essential to the Tumor-Promoting Role of TGF-beta.

Tripathi V, Sixt KM, Gao S, Xu X, Huang J, Weigert R, Zhou M, Zhang YE.
Molecular Cell. 64(5): 1010, 2016. [ Journal Article ]

Job Vacancies

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Team

Postdoctoral Fellow (Visiting)
Birendra Kc, Ph.D.
Research Fellow (Visiting)
Jee-Hye Shin, Ph.D.
Postbaccalaureate Fellow (CRTA)
Marie Spezia, M.S.
Biologist
Yi Tang, Ph.D.

Covers

Cover of Nature Medicine, January 8, 2012

A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20

Published Date

About the Cover:

The cover shows the co-localization of Smurf2 with DNA damage markers in the nuclei of human osteosarcoma cells.

Abstract:

In addition to allelic mutations, cancers are known to harbor alterations in their chromatin landscape. Here we show that genomic ablation of Smad ubiquitin regulatory factor 2 (Smurf2), a HECT-domain E3 ubiquitin ligase, results in dysregulation of both the DNA damage response and genomic stability, culminating in increased susceptibility to various types of cancers in aged mice. We show that Smurf2 regulates the monoubiquitination of histone H2B as well as the trimethylation of histone H3 at Lys4 and Lys79 by targeting ring finger protein 20 (RNF20) for proteasomal degradation in both mouse and human cells. We also show that Smurf2 and RNF20 are colocalized at the γ-H2AX foci of double-stranded DNA breaks in the nucleus. Thus, Smurf2 has a tumor suppression function that normally maintains genomic stability by controlling the epigenetic landscape of histone modifications through RNF20.

Citation

A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20. Blank M, Tang Y, Yamashita M, Burkett SS, Cheng SY, Zhang YE.  Nat Med. 2012 Jan 8;18(2):227-34.