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Exploring the molecular mechanisms controlling CDK7i sensitivity in pancreas cancer.

Award Number: F32CA284723
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Exploring the molecular mechanisms controlling CDK7i sensitivity in pancreas cancer. - PROJECT SUMMARY/ABSTRACT Pancreatic ductal adenocarcinoma (PDA) is projected to be the second leading cause of cancer deaths in the US by 2030. With no cost-effective screening or prevention measures, most newly diagnosed pancreas cancer patients present with locally advanced or metastatic disease, which carries a prognosis of less than one year. PDA is classified into classical and basal subtypes, with basal portending a worse survival. In preliminary data, we show that basal PDA is characterized by loss of the histone deacetylase sirtuin 6 (SIRT6) and inactivation of the Integrated Stress Response (ISR), which renders tumor cells more sensitive to CDK7 targeted therapies. SIRT6 has been recently shown to be a novel tumor suppressor in PDA, cooperating with oncogenic KRAS to drive an even more aggressive PDA. However, elucidating SIRT6’s role in modulating the ISR remains to be discovered. Here we propose three specific aims: (1) Identify how SIRT6 mechanistically affects ATF4 stability (2) Characterize the in vivo efficacy of CDK7i in clinically relevant PDA mouse models; and (3) Determine how DNp63 alters CDK7i sensitivity. This fellowship seeks support for the training of Dr. Adrianne Wallace-Povirk, a postdoctoral fellow at the Fred Hutchinson Cancer Center (Fred Hutch), toward her goal of pursuing an academic career in cancer research. To realize the scope of the proposed work, Dr. Wallace-Povirk will be sponsored by Dr. Sita Kugel, whose laboratory focuses on epigenetic dysregulation in pancreas cancer, and will also accelerate her research through collaborations with her co-mentor Dr. Andrew Hsieh (expert in translational regulation), Dr. Eric Collisson (recognized leader in pancreas subtyping research), Dr. Sunil Hingorani (a recognized leader in pancreas tumor biology and microenvironment), and Dr. Taran Gujral (expert in high- throughput drug screening design). Dr. Wallace-Povirk will benefit from the breadth of expertise and highly collaborative atmosphere at Fred Hutch, which houses leading research groups in pancreatic cancer and cancer therapeutics.


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	HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES	426 AUDITORIUM RD	EAST LANSING	MI	48824	INGHAM	USA	Cancer Research Manpower	000	2	11/24/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $75,052 )
2025	2025	HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES	426 AUDITORIUM RD	EAST LANSING	MI	48824	INGHAM	USA	Cancer Research Manpower	001	2	8/27/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$75,052
2025	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Research Manpower	000	1	8/26/2025	NEW	$0
														Subtotal = $75,052

Issue Date FY: 2024 ( Subtotal = $74,284 )
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Research Manpower	001	1	7/1/2024	NEW	$0
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Research Manpower	000	1	7/1/2024	NEW	$74,284
														Subtotal = $74,284

Grand Total All Awards = $149,336

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Exploring the molecular mechanisms controlling CDK7i sensitivity in pancreas cancer.

Award Number: F32CA284723

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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