Exploiting myeloma proteome remodeling to extend proteasome inhibitor efficacy

利用骨髓瘤蛋白质组重塑来延长蛋白酶体抑制剂的功效

基本信息

  • 批准号:
    10308238
  • 负责人:
  • 金额:
    $ 5.53万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-08-01 至 2023-02-28
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT This NCI Supplement to Promote Diversity is designed to support the career development of Ms. Audrey Kishishita, a second year student in the Chemistry and Chemical Biology Graduate Program at the University of California, San Francisco. Ms. Kishishita is of Latina descent and a first-generation college student who completed her undergraduate studies with high accolades at California State University-Los Angeles. The supplement is related to R01 CA226851, whose PI is Arun Wiita, MD, PhD. Dr. Wiita, an Associate Professor in the Dept. of Laboratory Medicine at UCSF, will serve as Ms. Kishishita's primary mentor for this proposal. The research plan of the Supplement directly relates to Aim 2 of the R01, which is focused on studying the role of alternative splicing in the blood cancer multiple myeloma. Specially, a major goal of this Aim in the R01 is to identify new ways to modulate splicing that may be beneficial either to perturb myeloma biology or potentially as a therapeutic. Here, Ms. Kishishita proposes experiments to develop novel recombinant protein fusion constructs that can enter myeloma cells and specifically degrade subunits of the spliceosome. She will first work to validate the principle of these degraders using GFP as a test substrate and then move on to engineering nanobody recognition elements for targeted splicing factors. She will further use mass spectrometry-based proteomics and mRNA-seq to evaluate downstream effects of this degradation. To complement the expertise of the primary mentor in myeloma biology, proteomics, splicing, and nanobody engineering, the co-mentor, Dr. Charles Craik, is a University Professor at UCSF with a >30 year track record of mentorship. Dr. Craik is also a leading expert in protein engineering and protein degradation, directly relevant to the proposal here. Drs. Wiita and Craik have worked with Ms. Kishishita to craft a comprehensive training plan including experiential learning, a series of both internal and external didactic courses, opportunities to present scientific work to receive feedback, experience in grant- and paper-writing, and opportunities for networking with peers and more experienced scientists. This training plan is designed to provide Ms. Kishishita with a unique skillset and scientific experience to carry her forward into her post-doctoral work and ultimately into an independent faculty position. We are excited to complete the proposal here to support the career development of a scientific trainee with outstanding potential.
项目总结/摘要 这个NCI补充,以促进多样性的目的是支持奥黛丽女士的职业发展 Kishishita是该大学化学和化学生物学研究生课程的二年级学生 来自加州的弗朗西斯科。岸下女士是拉丁裔,是第一代大学生, 在加州州立大学洛杉矶分校以优异成绩完成了本科学业。的 补充与R 01 CA 226851相关,其PI为Arun Wiita,MD,PhD。Wiita博士,副教授 在部门。加州大学旧金山分校的实验医学博士,将担任岸下女士的主要导师,为这一建议。 补编的研究计划与研究报告01的目标2直接相关,其重点是研究 选择性剪接在血癌多发性骨髓瘤中的作用。特别是,R 01中的这一目标的主要目标是 确定调节剪接的新方法,这些方法可能有益于干扰骨髓瘤生物学或潜在地 作为一种治疗。在这里,岸下女士提出了开发新型重组蛋白融合的实验 可以进入骨髓瘤细胞并特异性降解剪接体亚基的构建体。她会先 使用GFP作为测试底物,验证这些降解剂的原理,然后继续 工程化用于靶向剪接因子的纳米抗体识别元件。她将进一步利用质量 基于光谱的蛋白质组学和mRNA-seq来评估这种降解的下游影响。到 补充主要导师在骨髓瘤生物学、蛋白质组学、剪接和纳米抗体方面的专业知识 工程,共同导师,博士查尔斯克雷克,是一个大学教授在加州大学旧金山分校与超过30年的跟踪记录 导师制Craik博士也是蛋白质工程和蛋白质降解的领先专家,直接 与这里的提议有关。Wiita博士和Craik博士与Kishishita女士合作, 培训计划,包括体验式学习,一系列内部和外部教学课程, 有机会提出科学工作,以获得反馈,在赠款和论文写作的经验, 与同行和更有经验的科学家建立联系的机会。本培训计划旨在 为岸下女士提供独特的技能和科学经验,使她能够继续从事博士后工作 工作,并最终成为一个独立的教师职位。我们很高兴在这里完成提案, 支持具有杰出潜力的科学培训生的职业发展。

项目成果

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Arun P. Wiita其他文献

Cellular immunotherapy targeting CLL-1 for juvenile myelomonocytic leukemia
针对 CLL-1 的细胞免疫疗法用于幼年型粒单核细胞白血病
  • DOI:
    10.1038/s41467-025-59040-6
  • 发表时间:
    2025-04-23
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Juwita Werner;Alex G. Lee;Chujing Zhang;Sydney Abelson;Sherin Xirenayi;Jose Rivera;Khadija Yousuf;Hanna Shin;Bonell Patiño-Escobar;Stefanie Bachl;Kamal Mandal;Abhilash Barpanda;Emilio Ramos;Adila Izgutdina;Sibapriya Chaudhuri;William C. Temple;Shubhmita Bhatnagar;Jackson K. Dardis;Julia Meyer;Carolina Morales;Soheil Meshinchi;Mignon L. Loh;Benjamin Braun;Sarah K. Tasian;Arun P. Wiita;Elliot Stieglitz
  • 通讯作者:
    Elliot Stieglitz
Bladder cancer variants share aggressive features including a CA125+ cell state and targetable TM4SF1 expression
膀胱癌变异体具有侵袭性特征,包括 CA125+细胞状态和可靶向的 TM4SF1 表达
  • DOI:
    10.1038/s41467-025-59888-8
  • 发表时间:
    2025-06-17
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Heiko Yang;Hanbing Song;Elizabeth Yip;Timothy Gilpatrick;Kevin Chang;Paul Allegakoen;Kevin L. Lu;Keliana Hui;Julia H. Pham;Corynn Kasap;Vipul Kumar;Janae Gayle;Bradley A. Stohr;Chien-Kuang Cornelia Ding;Arun P. Wiita;Maxwell V. Meng;Jonathan Chou;Sima P. Porten;Franklin W. Huang
  • 通讯作者:
    Franklin W. Huang
Time-resolved proteomics vs. ribosome profiling reveals translation dynamics under stress
时间分辨蛋白质组学与核糖体分析揭示了压力下的翻译动态
  • DOI:
    10.1101/087486
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Tzu;Hector H. Huang;Diamond Wheeler;James A. Wells;Yun S. Song;Arun P. Wiita
  • 通讯作者:
    Arun P. Wiita
Tumour-wide RNA splicing aberrations generate actionable public neoantigens
肿瘤范围的 RNA 剪接异常产生可操作的公共新抗原
  • DOI:
    10.1038/s41586-024-08552-0
  • 发表时间:
    2025-02-19
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Darwin W. Kwok;Nicholas O. Stevers;Iñaki Etxeberria;Takahide Nejo;Maggie Colton Cove;Lee H. Chen;Jangham Jung;Kaori Okada;Senthilnath Lakshmanachetty;Marco Gallus;Abhilash Barpanda;Chibo Hong;Gary K. L. Chan;Jerry Liu;Samuel H. Wu;Emilio Ramos;Akane Yamamichi;Payal B. Watchmaker;Hirokazu Ogino;Atsuro Saijo;Aidan Du;Nadia R. Grishanina;James Woo;Aaron Diaz;Shawn L. Hervey-Jumper;Susan M. Chang;Joanna J. Phillips;Arun P. Wiita;Christopher A. Klebanoff;Joseph F. Costello;Hideho Okada
  • 通讯作者:
    Hideho Okada
DNA methyltransferase inhibitors upregulate CD38 protein expression and enhance daratumumab efficacy in multiple myeloma
DNA 甲基转移酶抑制剂上调多发性骨髓瘤中 CD38 蛋白表达并增强达雷木单抗疗效
  • DOI:
    10.1038/s41375-019-0587-5
  • 发表时间:
    2019-10-08
  • 期刊:
  • 影响因子:
    13.400
  • 作者:
    Priya Choudhry;Margarette C. Mariano;Huimin Geng;Thomas G. Martin;Jeffrey L. Wolf;Sandy W. Wong;Nina Shah;Arun P. Wiita
  • 通讯作者:
    Arun P. Wiita

Arun P. Wiita的其他文献

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{{ truncateString('Arun P. Wiita', 18)}}的其他基金

Structural Surfaceomics: A Strategy for Immunotherapy Target Discovery
结构表面组学:免疫治疗靶点发现的策略
  • 批准号:
    10290239
  • 财政年份:
    2021
  • 资助金额:
    $ 5.53万
  • 项目类别:
ClinTAD: A Tool for Improving Clinical CNV Interpretation
ClinTAD:改善临床 CNV 解读的工具
  • 批准号:
    10461112
  • 财政年份:
    2021
  • 资助金额:
    $ 5.53万
  • 项目类别:
Structural Surfaceomics: A Strategy for Immunotherapy Target Discovery
结构表面组学:免疫治疗靶点发现的策略
  • 批准号:
    10434121
  • 财政年份:
    2021
  • 资助金额:
    $ 5.53万
  • 项目类别:
ClinTAD: A Tool for Improving Clinical CNV Interpretation
ClinTAD:改善临床 CNV 解读的工具
  • 批准号:
    10286951
  • 财政年份:
    2021
  • 资助金额:
    $ 5.53万
  • 项目类别:
Exploiting myeloma proteome remodeling to extend proteasome inhibitor efficacy
利用骨髓瘤蛋白质组重塑来延长蛋白酶体抑制剂的功效
  • 批准号:
    10341162
  • 财政年份:
    2018
  • 资助金额:
    $ 5.53万
  • 项目类别:
Exploiting myeloma proteome remodeling to extend proteasome inhibitor efficacy
利用骨髓瘤蛋白质组重塑来延长蛋白酶体抑制剂的功效
  • 批准号:
    10524110
  • 财政年份:
    2018
  • 资助金额:
    $ 5.53万
  • 项目类别:
In vivo monitoring of oxidative protein folding through time-resolved quantitative mass spectrometry
通过时间分辨定量质谱法体内监测氧化蛋白折叠
  • 批准号:
    9167306
  • 财政年份:
    2016
  • 资助金额:
    $ 5.53万
  • 项目类别:
Global Assessment of Myeloma Response to Chemotherapy
骨髓瘤化疗反应的整体评估
  • 批准号:
    8819976
  • 财政年份:
    2014
  • 资助金额:
    $ 5.53万
  • 项目类别:
Global Assessment of Myeloma Response to Chemotherapy
骨髓瘤化疗反应的整体评估
  • 批准号:
    8928081
  • 财政年份:
    2014
  • 资助金额:
    $ 5.53万
  • 项目类别:
Global Assessment of Myeloma Response to Chemotherapy
骨髓瘤化疗反应的整体评估
  • 批准号:
    9337420
  • 财政年份:
    2014
  • 资助金额:
    $ 5.53万
  • 项目类别:

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Alternative splicing of Grin1 controls NMDA receptor function in physiological and disease processes
Grin1 的选择性剪接控制生理和疾病过程中的 NMDA 受体功能
  • 批准号:
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长非编码 RNA H19 介导 ALD 发病机制中的选择性剪接
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选择性剪接作为表型可塑性的进化驱动力
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CAREER: Mechanotransduction, transcription, and alternative splicing in cell biology
职业:细胞生物学中的机械转导、转录和选择性剪接
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