Initiation of diffuse and intestinal non-cardia gastric cancer

Active Project Grant Awarded Last action

Award ID
R01CA272891
Recipient
Awarding agency
Obligated
$8,047,491

Award facts

Assistance listing
93.396 Cancer Biology Research
Completion date 83% complete
Place of performance
New York, NY 10032, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Gastric cancer (GC), the third leading cause of cancer death worldwide, is characterized both by histologic and molecular criteria. The two most common forms include diffuse GC (DGC) and intestinal GC (IGC). Each class of GC is associated with early inactivation of a distinct tumor suppressor, CDH1 (encoding E-cadherin) for DGC and P53 for IGC. Beyond genetic changes, gastric cancer development is promoted by environmental factors, specifically helicobacter infection and exposure to dietary nitrates. We posit that addressing two fundamental questions in the gastric cancer field: defining the cells-of-origin and defining the distinct mediators of progression, should be addressed together given their interconnectedness. We will evaluate the interplay of genetic and environmental precipitants to gastric cancer using novel engineered mouse models where we can selectively target key tumor suppressors in the gastric epithelium in concert with relevant exposures. We will then deeply interrogate tissues with the combination of multi-omic single cell technologies enabling dual analysis of gene expression and chromatin accessibility in individual cells and the subsequent use of spatial transcriptomic tools allowing US to map features of individual cell types spatially to refine the cellular origins of these altered cell types. In concert to defining cellular origins of the two primary classes of gastric cancer, our integrated multi-omic and spatial analyses will be evaluated to define changes in cellular programs and candidate mediators of these altered phenotypes. In addition, we will explore how coevolving changes in the gastric microenvironment may accompany or promote the cell's precancerous transformation. We will better define the interaction of environmental exposures in gastric tumorigenesis and investigate interactions of resulting early mutations with environmental factors, testing our hypothesis that this interaction modulates both gastric cells and microenvironment. Utilizing our cellular and spatial profiling, we will generate a map of the microenvironment showing the development of the disease in its spatial context, which will also be a resource for future studies. To generalize our findings in the mouse to human, we will perform single cell multi-OME analysis of human and mouse derived organoids and expand our existing single cell atlas of the human GI tract. Subsequently, we will perform functional validation of candidate mediators of progression, evaluating both features intrinsic to gastric epithelial cells and those emerging from the microenvironment. These studies will both address longstanding debates over origins of gastric cancers as well as define new targets to prevent cancer development.

Transactions

Action Obligated Date
Amendment $927,993
Amendment $98,559
Amendment $59,881
Amendment $898,099
Amendment $0
Amendment $0
Amendment $0
Amendment $1,073,015
Amendment $67,328
Amendment $1,073,015
Amendment $67,328
Amendment Elucidating the mechanisms by which the extracellular matrix contribute to gastroesophageal cancer pathobiology $15,925
Amendment $15,925
Amendment $15,925
Amendment $0
Amendment Elucidating the mechanisms by which the extracellular matrix contribute to gastroesophageal cancer pathobiology $0
Amendment $0
Amendment $0
Amendment $908,985
Amendment $908,985
Amendment $0
Amendment $0
Amendment $0
Amendment $0
Amendment $958,264
Original award $958,264
Show all 26

Subawards

Subrecipient Amount Awarded
Deutsches Krebsforschungszentrum In the course of the study, we aim to perform deep molecular characterization of mouse models defined by genetic changes associated with early tumorigenic… $98,559
New York Genome Center, Inc. The scope of work to be carried out by the sub-award at New York Genome Center as part of this project consists of generating and analyzing single nucleus and… $492,405
Deutsches Krebsforschungszentrum Statement of Work for subcontract between DKFZ and Columbia University for NIH grant project 5R01CA272891-02 titled Initiation of Diffuse and Intestinal… $98,305
New York Genome Center, Inc. The scope of work to be carried out by the sub-award at New York Genome Center as part of this project consists of generating and analyzing single nucleus and… $425,730
Deutsches Krebsforschungszentrum Costs Statement of Work for subcontract between DKFZ and Columbia University for NIH grant project 5R01CA272891-02 􀆟tled Ini􀆟a􀆟on… $98,631
New York Genome Center, Inc. ô€€¶ô€€¦ô€€²ô€€³ô€€¨ô€€ƒô€€²ô€€©ô€€ƒô€€ºô€€²ô€€µô€€®ô€€ƒô€€‰ô€€ƅ $347,062

Quick answers

Who received award R01CA272891?

R01CA272891 was awarded to The Trustees Of Columbia University In The City Of New York by National Cancer Institute (National Institutes of Health) on September 1, 2022.

How much is award R01CA272891 worth?

$8,047,491 has been obligated on R01CA272891.

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