Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Identification and Characterization of Novel Cis-Regulatory Elements Controlling PTEN Expression

Award Number: F30CA247323
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2022

Group Awards By:

View Award Description

Identification and Characterization of Novel Cis-Regulatory Elements Controlling PTEN Expression - Abstract It is increasingly appreciated that the non-coding genome can shape gene expression and, consequently, diseases such as cancer. Beyond a few select examples, however, we know remarkably little about the specific cis- regulatory mechanisms influencing many key oncogenes and tumor suppressors. While various approaches to identify candidate cis-regulatory elements (ccREs) on a genome-wide scale have been successful in nominating large sets putative regulatory regions, many such methods rely on indirect evidence or evidence gleaned outside of the native context of the cell. Further, pairing the regulatory activity of a given ccRE with its gene partners has proven difficult. To address this, our groups created the first technologies for functionally defining the regulatory circuitry of specific genes, CRISPR-Cas9-Based Epigenomic Regulatory Element Screening (CERES). This platform utilizes nuclease-deactivated (d)Cas9 coupled to epigenomic activator (p300) and repressor (KRAB) constructs. These constructs are paired with lentiviral short guide RNA (sgRNA) libraries targeting areas of accessible chromatin surrounding a gene of interest. Thus, we are able to map the effect of both activation and repression of candidate loci on the expression of a target gene, and thereby define the regulatory elements for that gene. Powered by this unique in-house technological approach, we are now interested in defining the endogenous mechanisms controlling expression of important cancer genes. One of the most frequently altered tumor suppressor genes (TSGs) in human cancers is phosphatase and tensin homolog (PTEN), which encodes a lipid and protein phosphatase that negatively regulates the PI3K-AKT pathway, among others. PTEN is mutated or deleted at the genetic level in many tumors. However, a large fraction of patients exhibit loss of PTEN expression without these associated genetic alterations, suggesting a potential role for non-coding alterations controlling PTEN expression. Separately, it is also known that overexpression of PTEN is sufficient to inhibit cancer cell proliferation, drive apoptosis, and stimulate immune surveillance. Therefore, techniques which target endogenous PTEN for overexpression, for instance through the manipulation of its cis-acting regulatory elements (cREs), could represent a promising therapeutic strategy. In this proposal, we will systematically define the key cREs controlling PTEN expression. In so doing, we will provide a foundation for understanding the role of non-coding mutations as drivers of PTEN loss in human tumors and germline tumor syndromes. Further, this work will establish a foundation for identifying the transcription factors and signaling pathways that regulate PTEN expression through these critical cREs, work which could enable the eventual design of therapeutics that target its genetic regulation.


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: 2024 ( Subtotal = $0 )
2024	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cancer Research Manpower	000	3	10/31/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $40,892 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Research Manpower	001	3	4/7/2022	NON-COMPETING CONTINUATION	$2,500
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Research Manpower	002	3	6/22/2022	NON-COMPETING CONTINUATION	$716
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Research Manpower	000	3	12/2/2021	NON-COMPETING CONTINUATION	$37,676
														Subtotal = $40,892

Issue Date FY: 2021 ( Subtotal = $37,676 )
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Research Manpower	000	2	12/11/2020	NON-COMPETING CONTINUATION	$37,160
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Research Manpower	001	2	2/3/2021	NON-COMPETING CONTINUATION	$516
														Subtotal = $37,676

Issue Date FY: 2020 ( Subtotal = $50,520 )
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Research Manpower	002	1	2/11/2020	NEW	$504
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Research Manpower	000	1	12/10/2019	NEW	$50,016
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cancer Research Manpower	001	1	12/10/2019	NEW	$0
														Subtotal = $50,520

Grand Total All Awards = $129,088

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Identification and Characterization of Novel Cis-Regulatory Elements Controlling PTEN Expression

Award Number: F30CA247323

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2022

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer