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Ettore  Appella, M.D.

Ettore Appella, M.D.

  • Center for Cancer Research
  • National Cancer Institute
Laboratory of Cell Biology

RESEARCH SUMMARY

Dr. Appella was among the first researchers to identify the tumor suppressor protein p53, and he has studied its roles in the cell and regulation by post-translational modification. He and his colleagues further identified a critical phosphatase that is upregulated by p53 following DNA damage. This phosphatase, Wip1 (PPM1D), is amplified or overexpressed in several human tumors. Dr. Appella’s research currently is focused on exploring the roles of Wip1 in cells and its contribution to tumorigenesis. They additionally are exploring how Wip1 is regulated. Finally, Dr. Appella’s laboratory is working to develop specific inhibitors of Wip1 that could be advanced to the clinic.

Areas of Expertise

p53
Wip1 Phosphatase
Protein Chemistry
Mass Spectrometry

Publications

Selected Recent Publications

Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma

Veschi V, Liu Z, Voss TC, Ozbun L, Gryder B, Yan C, Hu Y, Ma A, Jin J, Mazur SJ, Lam N, Souza BK, Giannini G, Hager GL, Arrowsmith CH, Khan J, Appella E, Thiele CJ.
Cancer Cell. 31(1): 50-63, 2017. [ Journal Article ]

Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246

Cooks T, Pateras IS, Jenkins LM, Patel KM, Robles AI, Morris J, Forshew T, Appella E, Gorgoulis VG, Harris CC.
Nat Commun.. 9(1): 771, 2018. [ Journal Article ]

Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens

Clausse V, Tao D, Debnath S, Fang Y, Tagad HD, Wang Y, Sun H, LeClair CA, Mazur SJ, Lane K, Shi ZD, Vasalatiy O, Eells R, Baker LK, Henderson MJ, Webb MR, Shen M, Hall MD, Appella E, Appella DH, Coussens NP
J Biol Chem. 294: 17654-17668, 2019.
Full-Text Article
[ Journal Article ]

Inhibition of the DNA damage response phosphatase PPM1D reprograms neutrophils to enhance anti-tumor immune responses

Uyanik B, Goloudina AR, Akbarali A, Grigorash BB, Petukhov AV, Singhal S, Eruslanov E, Chaloyard J, Lagorgette L, Hadi T, Baidyuk EV, Sakai H, Tessarollo L, Ryffel B, Mazur SJ, Lirussi F, Garrido C, Appella E, Demidov ON
Nat Commun. 12: 3622, 2021.
Full-Text Article
[ Journal Article ]

Targeting mutant p53-R248W reactivates WT p53 function and alters the onco-metabolic profile

Brown K, Jenkins LMM, Crooks DR, Surman DR, Mazur SJ, Xu Y, Arimilli BS, Yang Y, Lane AN, Fan TW, Schrump DS, Linehan WM, Ripley RT, Appella E.
Front Oncol. 12: 1094210, 2023.
Full-Text Article
[ Journal Article ]

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Team

Research Fellow
Kate Brown, Ph.D.
Postdoctoral Fellow (Visiting)
Jay Prakash Kumar, Ph.D.
Postdoctoral Fellow (Visiting Fellow)
Pierre Martine
Predoctoral Visiting Fellow (Graduate Student)
David Lopez Perez

News

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