Saturday, March 14, 2026 3/14/2026

Engineering Native E. coli to Detect, Report, and Treat Colorectal Cancer

Award Number: U01CA265719
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/21/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Engineering Native E. coli to Detect, Report, and Treat Colorectal Cancer - PROJECT SUMMARY/ABSTRACT Despite its overall decreasing occurrence, colorectal cancer (CRC) remains the fourth most common cause of cancer deaths in the US. Unfortunately, epidemiological studies demonstrate an alarming increase in inci- dence in populations below the age of 50, who are not routinely screened. Furthermore, CRC detection is difficult in high-risk groups, including those with a genetic predisposition (e.g. familial adenomatous polyposis), disease traits (e.g. inflammatory bowel disease), or from certain demographics (e.g. Black-Americans). Thus, there is a significant need for the development of innovative solutions for the early detection of CRC and the prevention of the transition from adenoma to CRC. To address this need, our interdisciplinary research team will develop genetically engineered bacteria using synthetic biology approaches to identify early CRC development, monitor and report changes in the adenoma and CRC microenvironment, and prevent cancer progression. To achieve the above objectives, engineered bacteria have to engraft and colonize the hostile luminal environment, sense and distinguish an abnormal environmental signal, compute this signal, and express a reporter or a therapeutic agent. However, appropriate vectors with these features remain lacking, constraining synthetic biology applica- tions for cancer research. Importantly, CRC is highly associated with E. coli, for which we have many synthetic biology tools. Furthermore, our preliminary proof-of-concept studies have revealed that native E. coli can be engineered to perpetually colonize fully conventional (i.e. non-microbiome depleted) hosts and to execute func- tions of interest, e.g., deconjugation of luminal bile acids. Deconjugated bile acid and resultant farnesoid X re- ceptor (FXR) agonism can suppress CRC development, indicating a potential therapeutic use of engineered native bacteria. Building on our strong supportive preliminary results, we will identify native E. coli from healthy, adenoma, and CRC tissues of a genetic model of CRC and engineer them to detect and treat CRC in response to the cancer microenvironment. Furthermore, we will characterize the effects of different tumor environment factors on the colonization and performances of engineered native E. coli in the colon organoid model in an organ-on-chip with the support of mathematical modeling, thereby identifying specific CRC signals for program- ming the responses of engineered native E. coli as CRC reporters and therapeutics. Finally, we will engineer native bacteria to detect and attenuate the progression of CRC by quantitatively reporting the level of CRC- related cysteine proteases and selectively inhibiting their activity. The research described in this proposal will generate new, much-needed synthetic biology vectors that can be developed as biosensors and therapeutics of adenoma and CRC, as well as many other diseases. Furthermore, this project will enrich our fundamental knowledge about the CRC-microbiome relationship and elucidate the roles of cysteine proteases in CRC pro- gression and treatment.


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: 2026 ( Subtotal = $0 )
2026	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	000	5	2/27/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $625,751 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	001	5	8/11/2025	NON-COMPETING CONTINUATION	$625,751
2025	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	000	4	2/14/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $625,751

Issue Date FY: 2024 ( Subtotal = $594,784 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	002	4	9/5/2024	NON-COMPETING CONTINUATION	$594,784
2024	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	001	3	6/6/2024	NON-COMPETING CONTINUATION	$0
2024	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	000	3	4/29/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $594,784

Issue Date FY: 2023 ( Subtotal = $613,187 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	000	3	9/8/2023	NON-COMPETING CONTINUATION	$613,187
														Subtotal = $613,187

Issue Date FY: 2022 ( Subtotal = $619,234 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	001	2	9/7/2022	NON-COMPETING CONTINUATION	$619,234
2022	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	000	1	7/19/2022	NEW	$0
														Subtotal = $619,234

Issue Date FY: 2021 ( Subtotal = $682,384 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	001	1	9/24/2021	NEW	$0
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	000	1	9/21/2021	NEW	$682,384
														Subtotal = $682,384

Grand Total All Awards = $3,135,340

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Engineering Native E. coli to Detect, Report, and Treat Colorectal Cancer

Award Number: U01CA265719

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/21/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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