Regulatory control of inflammatory cytokine production by a linear ubiquitin-binding protein

线性泛素结合蛋白对炎症细胞因子产生的调节控制

基本信息

  • 批准号:
    10337076
  • 负责人:
  • 金额:
    $ 7.69万
  • 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:
    2021-02-02 至 2022-07-29
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT This proposal outlines a five-year plan for the PI, Dr. Alexander Gitlin, to prepare him for an independent academic career as a physician-scientist. Dr. Gitlin received his M.D./Ph.D. degrees from the Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional M.D.-Ph.D. program and is currently completing residency in Clinical Pathology at Stanford Hospital and Clinics. During residency, Dr. Gitlin developed a jointly mentored research program, co-advised by Drs. Bali Pulendran (Stanford University) and Vishva Dixit (Genentech, Inc.). Drs. Pulendran and Dixit are longtime colleagues and collaborators with highly complementary expertise. Dr. Pulendran is an expert in toll-like receptors, innate immunity, and dendritic cells; Dr. Dixit is an expert on inflammatory signaling, cell death, and ubiquitin biology. Both Drs. Pulendran and Dixit have served as mentors to numerous trainees, many of whom have become leading investigators in academia or industry. This joint mentorship program provides Dr. Gitlin with full access to the combined resources and expertise present at two neighboring, world-class research institutions, Stanford University and Genentech, which will provide outstanding environments for Dr. Gitlin to develop his own independent scientific career. In addition, Dr. Gitlin has assembled a K08 advisory committee composed of senior investigators whose scientific expertise and mentorship will greatly aid Dr. Gitlin’s career development. They include Drs. Stephen Galli, Denise Monack, Scott Boyd, and Andrey Shaw. Furthermore, Dr. Gitlin will have access to coursework, retreats, seminars and resources through Stanford University’s School of Medicine, The Stanford Office of Postdoctoral Affairs, and the Genentech Postdoctoral Program. Finally, the scientific resources available to Dr. Gitlin comprise the Pulendran/Dixit laboratories and core facilities at both Stanford University and Genentech, representing an extraordinary set of scientific resources. The research proposal detailed herein seeks to uncover the molecular mechanisms by which linear ubiquitin controls the magnitude of the innate immune response. Dysregulated inflammatory and cytokine responses are fundamental features of multiple chronic diseases, including autoimmunity, autoinflammatory syndromes, infectious diseases, immunodeficiencies and cancer. Yet, many of the complex signaling pathways that regulate inflammatory signaling are still being unraveled at a mechanistic level. During Dr. Gitlin’s short time as a co-mentee of Drs. Dixit and Pulendran, he has discovered that the NEDD4-binding protein 1 (N4BP1), a linear ubiquitin-binding protein, is a novel regulator of toll-like receptor (TLR) responses. In Aim 1, we will test the hypothesis that N4BP1 differentially regulates inflammatory cytokine production downstream of TLR signaling. In Aim 2, we will dissect the mechanistic basis of N4BP1 activity by inactivating its independent functional motifs. We anticipate these studies will elucidate a novel pathway by which a previously enigmatic linear ubiquitin-binding protein selectively controls the cytokine output of TLRs. These studies provide an excellent platform for Dr. Gitlin to complete his training and launch his independent career.
项目总结/文摘

项目成果

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Alexander Gitlin其他文献

Alexander Gitlin的其他文献

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{{ truncateString('Alexander Gitlin', 18)}}的其他基金

Regulation of Proinflammatory Cytokine Responses by a Caspase-8-N4BP1 Axis
Caspase-8-N4BP1 轴对促炎细胞因子反应的调节
  • 批准号:
    10704065
  • 财政年份:
    2022
  • 资助金额:
    $ 7.69万
  • 项目类别:
Regulatory control of inflammatory cytokine production by a linear ubiquitin-binding protein
线性泛素结合蛋白对炎症细胞因子产生的调节控制
  • 批准号:
    10674329
  • 财政年份:
    2021
  • 资助金额:
    $ 7.69万
  • 项目类别:
Molecular Regulation of Germinal Center B Lymphocytes
生发中心 B 淋巴细胞的分子调控
  • 批准号:
    8649227
  • 财政年份:
    2014
  • 资助金额:
    $ 7.69万
  • 项目类别:

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