Monday, June 30, 2025 6/30/2025

Grb7 protein function and conformation

Award Number: SC3GM116728
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/20/2016
PERIOD OF PERFORMANCE END DATE: 06/30/2022

Group Awards By:

View Award Description

Grb7 protein function and conformation - DESCRIPTION (provided by applicant): Our goal is to define Grb7 function at the atomic level and to form mechanistic hypotheses for Grb7 function and regulation. Through this research we aim to bridge the large gap between high-resolution structural detail and cancer development and progression involving the Grb7 protein. Grb7 is principally known as a promoter of tumor progression through regulation of cell migration signaling mediated by the FAK (focal adhesion kinase) and the EphB1 receptor tyrosine kinase (RTK). In a particularly difficult to treat subset o breast cancers, known as triple negative breast cancer (TNBC), Grb7 expression is associated with an increased risk of recurrence after treatment. A Grb7V protein variant, lacking its C-terminal SH2 domain, has been linked to invasive human esophageal carcinoma and high- grade ovarian cancer. Interest in Grb7 as a cancer marker and potential therapeutic target has accelerated. In 2002, ten years after the initial discovery of the Grb7 protein through CORT (cloning of receptor targets) screening, references citing Grb7 numbered less than 20. At the current time this number has risen to greater than 220. Given its importance in cancer and inflammation, the Grb7 protein has become a subject for targeted therapy, and efforts have been made to develop Grb7 selective inhibitors. No clinical therapeutics presently exist targeting Grb7, however, translational research has yielded small cyclic peptide Grb7 inhibitors that decrease cell migration rates and proliferation in cancer cell lines. Though useful as drug models, these inhibitors bind with lower affinity than peptides representative of natural Grb7 binding sites. At present, no further real advances toward achieving therapeutically effective Grb7 inhibitors has occurred. Detailed knowledge of the mechanism of Grb7 function in signaling pathways driven by Grb7 overexpression remains largely incomplete. Through the studies outlined in this proposal we will define how the RA-PH, and SH2 protein domains work within Grb7 to regulate the oligomeric and conformational state of the intact protein. Additionally we will resolve whether the Grb7 activated functional form is monomeric, or dimeric, and whether it is controlled by tyrosine phosphorylation status. To achieve the goals of this proposal we will accomplish the following specific aims: Specific Aim 1. : Characterization of the functional state of the Grb7 protein with respect to tyrosine phosphorylation state, oligomerization, and ability to interact with other protein signaling partners. Specific Aim 2: Investigation of Grb7 protein interdomain binding interfaces, binding kinetics, and full-length dimerization deficient Grb7.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = -$55,156 )
2023	2019	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST.	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	000	4	11/9/2022	NON-COMPETING CONTINUATION	-$55,156
														Subtotal = -$55,156

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST STE E1200	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	000	4	8/19/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $111,000 )
2019	2019	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST STE E1200	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	000	4	6/21/2019	NON-COMPETING CONTINUATION	$111,000
														Subtotal = $111,000

Issue Date FY: 2018 ( Subtotal = $111,000 )
2018	2018	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST STE E1200	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	000	3	6/27/2018	NON-COMPETING CONTINUATION	$111,000
														Subtotal = $111,000

Issue Date FY: 2017 ( Subtotal = $111,000 )
2017	2017	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST STE E1200	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	000	2	6/30/2017	NON-COMPETING CONTINUATION	$111,000
														Subtotal = $111,000

Issue Date FY: 2016 ( Subtotal = $111,000 )
2016	2016	NEW MEXICO STATE UNIVERSITY	P.O. BOX 30001-MSC 3AA	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	000	1	7/21/2016	NEW	$111,000
														Subtotal = $111,000

Grand Total All Awards = $388,844

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Grb7 protein function and conformation

Award Number: SC3GM116728

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/20/2016

PERIOD OF PERFORMANCE END DATE: 06/30/2022

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer