Oncogenic mechanisms, molecular stratification and therapeutic targets of brain tumors
Oncogenic mechanisms, molecular stratification and therapeutic targets of brain tumors
批准号:
10729917
负责人:
Antonio Iavarone
金额:
$82.74万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-09-24 至 2028-08-31
中文摘要
摘要
英文摘要
Abstract
The work to be pursued in this application will continue and expand the program pioneered by Dr. Iavarone to
combine innovative computational tools and state-of-the-art experimental cancer models in vitro and in vivo to
identify homogeneous subgroups of cancer patients in order to dissect the pathogenesis of cancer and design
tailored and fully validated personalized therapeutic approaches. The application is focused on glioblastoma
multiforme, one of the most lethal forms of human cancer. The investigation of glioblastoma has represented a
long-standing effort of Dr. Iavarone’s laboratory, which in recent work has produced novel targeted therapeutic
opportunities currently being tested in clinical studies. The proposal will also benefit from the organizational
contexts recently set in motion by the large network operations coordinated by the PI. The research plan is
articulated around the development of a novel and integrated computational-experimental framework for: i) the
identification of homogeneous groups of tumors sharing activation of the same biological pathways; ii) the study
of cancer heterogeneity at the single cell level to accurately inform tumor classifications; iii) the therapeutic
prediction emerging from the identification of driver modules and synthetic lethal relationships of malignant
glioma. We will develop and apply novel technologies for high-throughput transcriptomic and proteomic analysis
of individual cells within malignant glioma tissues. These approaches, which we have pioneered in our laboratory
at Columbia University during the last few years, will serve as the basis for the multifaceted computational
analysis that will extract genes and proteins responsible for the phenotypic state of individual cells. Experimental
validations will be selectively applied to the novel and most exciting molecular pathways and will be performed
by our laboratory that has an array of experimental tools and sequence-annotated patient-derived models to
pursue each individual question. As for the selection of oncogene-dependent and independent vulnerabilities
identified by our previous work, the ability of our studies to identify novel driver phenotypes and master regulators
of individual tumor cells will be geared towards routing the new mechanisms into pathway-based synthetic
lethality that will inform specific drug sensitivities. The successful outcome of this proposal is an integrated
computational-experimental pipeline that will be able to mechanistically identify the determinants of tumor
genomes and phenotypes of solid tumors. This information will be of invaluable significance to decipher evolving
tumor dependencies and provide the most accurate therapeutic predictions.
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Evolution and targeting of the functional states of glioblastoma
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批准号:10467181
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项目类别:
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资助金额:$25.65万
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财政年份:2022
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负责人:Antonio Iavarone
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依托单位:
Evolution and targeting of the functional states of glioblastoma
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批准号:10651751
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资助金额:$39.36万
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财政年份:2022
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负责人:Antonio Iavarone
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依托单位:
Evolution and targeting of the functional states of glioblastoma
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批准号:10729932
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项目类别:
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资助金额:$16.23万
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财政年份:2022
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负责人:Antonio Iavarone
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依托单位:
Oncogenic mechanisms, molecular stratification and therapeutic targets of brain tumors
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批准号:10493186
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项目类别:
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资助金额:$12.52万
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财政年份:2021
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负责人:Antonio Iavarone
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依托单位:
Oncogenic mechanisms, molecular stratification and therapeutic targets of brain tumors
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批准号:10299894
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资助金额:$66.32万
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财政年份:2021
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负责人:Antonio Iavarone
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依托单位:
Oncogenic mechanisms, molecular stratification and therapeutic targets of brain tumors
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批准号:10675651
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项目类别:
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资助金额:$82.48万
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财政年份:2021
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负责人:Antonio Iavarone
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The Huwe1 ubiquitin ligase regulates mitosis, genomic stability and oncogenesis.
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批准号:10188467
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项目类别:
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资助金额:$37.06万
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财政年份:2019
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负责人:Antonio Iavarone
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依托单位:
The role of the LZTR1 ubiquitin ligase in stem cells and cancer
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批准号:9262886
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项目类别:
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资助金额:$38.31万
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财政年份:2015
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负责人:Antonio Iavarone
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依托单位:
The role of the LZTR1 ubiquitin ligase in stem cells and cancer
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批准号:9067257
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项目类别:
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资助金额:$38.97万
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财政年份:2015
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负责人:Antonio Iavarone
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依托单位:
Project 2: Dissection of clonal architecture and evolution in solid tumors
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批准号:8866153
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项目类别:
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资助金额:$36.93万
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财政年份:2015
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负责人:Antonio Iavarone
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依托单位:
Topology of Cancer Evolution and Heterogeneity
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批准号:8866149
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项目类别:
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资助金额:$199.09万
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财政年份:2015
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负责人:Antonio Iavarone
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依托单位:
The mechanisms driving brain oncogenesis by FGFR-TACC gene fusions
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批准号:9265417
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项目类别:
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资助金额:$36.69万
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财政年份:2014
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负责人:Antonio Iavarone
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依托单位:
The mechanisms driving brain oncogenesis by FGFR-TACC gene fusions
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批准号:8773917
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项目类别:
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资助金额:$37.6万
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财政年份:2014
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负责人:Antonio Iavarone
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依托单位:
The mechanisms driving brain oncogenesis by FGFR-TACC gene fusions
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批准号:8884561
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项目类别:
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资助金额:$37.28万
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财政年份:2014
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负责人:Antonio Iavarone
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依托单位:
Identification and modeling of driver genetic modules in glioblastoma
-
批准号:8632597
-
项目类别:
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资助金额:$45.96万
-
财政年份:2013
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负责人:Antonio Iavarone
-
依托单位:
Computational analysis of Human High Grade Gliomas
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批准号:8144783
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项目类别:
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资助金额:$49.7万
-
财政年份:2009
-
负责人:Antonio Iavarone
-
依托单位:
Computational analysis of Human High Grade Gliomas
-
批准号:8327774
-
项目类别:
-
资助金额:$47.51万
-
财政年份:2009
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负责人:Antonio Iavarone
-
依托单位:
Computational analysis of Human High Grade Gliomas
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批准号:7761428
-
项目类别:
-
资助金额:$46.65万
-
财政年份:2009
-
负责人:Antonio Iavarone
-
依托单位:
Computational analysis of Human High Grade Gliomas
-
批准号:8526579
-
项目类别:
-
资助金额:$45.78万
-
财政年份:2009
-
负责人:Antonio Iavarone
-
依托单位:
Computational analysis of Human High Grade Gliomas
-
批准号:7921441
-
项目类别:
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资助金额:$47.66万
-
财政年份:2009
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负责人:Antonio Iavarone
-
依托单位:
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