第774回 生医研セミナー(多階層生体防御システム研究拠点)

下記の通り、Shelley L. Berger 先生によるセミナーを開催致します。
Berger 先生は癌および脳機能におけるエピゲノム研究の第一人者です。皆様のご来聴を心より歓迎いたします。

※セミナーは英語で行われます。(Seminar in English)


演題 / Title

Epigenetic pathways as targets in human disease

演者 / Speaker

Prof. Shelley L. Berger
Epigenetics Institute, Departments of Cell and Developmental Biology, Genetics, Biology,
University of Pennsylvania
Philadelphia, PA, USA

日時 / Date

2018年9月5日(水) Sep. 5 (Wed), 2018
17:00~18:00

場所 / Venue

病院キャンパス 生体防御医学研究所 本館1階 会議室
以下の地図の31番です。
(http://www.kyushu-u.ac.jp/f/33951/2018hospital_2.pdf)

Seminar Room, 1F, Main Building, Medical Institute of Bioregulation, Hospital Campus
No.31 on the following linked map.
(http://www.kyushu-u.ac.jp/f/33952/2018hospital_2-en.pdf)

要 旨 / Abstract

 Chromatin regulatory proteins are frequently mutated in human disease. Because they are enzymes, chromatin proteins are outstanding targets for drug development. We elucidate epigenetic pathways that drive human cancer and brain function.
 Our cancer research focuses on epigenetic mechanisms underlying function of the tumor suppressor p53 and underlying patient response to immunotherapy. Our work has revealed that common p53 mutations co-opt epigenetic pathways to drive cancer. Other cancers retain wild type p53, and repressive p53 protein modifications restrain its normal activity. In cancer immunotherapy, we study T cell checkpoint inhibitor therapy and chimeric antigen receptor (CAR) T cell therapy, to determine epigenetic pathways leading to poor, or to exceptional patient response.
 We study neuroepigenetics in the mouse brain, investigating a novel pathway of nuclear metabolic production of acetyl-CoA, the cofactor for histone acetylation. We discovered that an enzyme generating acetyl-CoA (ACSS2) is directly bound to chromatin at critical immediate early neuronal genes, directly fuels the enzyme that catalyzes histone acetylation (CBP), and is critically important to hippocampal-mediated cognitive plasticity. This is a novel paradigm of transcriptional regulation in which ACSS2 functions as a chromatin-bound coactivator that locally provides acetyl-CoA to promote histone acetylation and neuron-specific transcription for learning and memory.

参考文献 / References

Zhu J, Sammons MA, Donahue G, Dou Z, Vedadi M, Getlik M, Barsyte-Lovejoy D, Al-Awar R, Katona BW, Shilatifard A, Huang J Hua X, Arrowsmith CH, and Berger SL. (2015)
Gain-of-function p53 mutants co-opt epigenetic pathways to drive cancer growth.
Nature 525:206-11. PMCID: PMC4568559.

Dou Z, Ghosh K, Vizioli MG, Zhu J, Sen P, Wangensteen KJ, Simithy J, Lan Y, Lin Y, Zhou Z, Capell BC, Xu C, Xu M, Kieckhaefer JE, Jiang T, Shoshkes-Carmel M, Tanim KM, Barber GN, Seykora JT, Millar SE, Kaestner KH, Garcia BA, Adams PD, and Berger SL. (2017)
Cytoplasmic chromatin triggers inflammation in senescence and cancer.
Nature, 550:402-406. PMID:28976970.

Mews, P, Donahue G, Drake A, Luczak V, Abel T, and Berger SL. (2017)
Acetyl-CoA metabolism by ACSS2 regulates neuronal histone acetylation and hippocampal memory.
Nature, 546,381-386. PMCID: PMC5505514.

連絡先 / Contact

生体防御医学研究所 エピゲノム制御学分野
佐々木 裕之
092(642)6759

Division of Epigenomics and Development, MIB
Hiroyuki SASAKI
092(642)6759