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Regulation of Mammary Gland Development by Sirtuin 4

Award Number: SC2GM141997
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: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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Regulation of Mammary Gland Development by Sirtuin 4 - Project Summary The mitochondrial enzyme sirtuin 4 (SIRT4) is downregulated in breast cancer tissue, but the reason for this is not clear. In order to elucidate this, we first sought to determine the role of SIRT4 in normal mammary tissue. We have discovered that SIRT4 is critical for ensuring normal mammary development. In mice with a total lack of SIRT4 (SIRT4KO mice), mammary glands do not fully develop during puberty. As a result, they do not produce enough maternal breast milk during pregnancy and nearly 100% of their young perish two days after birth. We now seek to uncover the mechanism by which SIRT4 influences mammary gland development. First, we seek to investigate the potential role of the ovarian hormones 17β-estradiol (E2) and progesterone (P4) in mediating the effects of SIRT4 on mammary development (Aim 1). These two hormones are essential for initiating growth of milk-producing mammary ducts during puberty and pregnancy and the mammary defects seen in SIRT4KO mice are reminiscent of the defects seen in mice with disrupted E2 or P4 signaling. Furthermore, since SIRT4 is found in mitochondria and is known to have many metabolic effects, we seek to investigate the possibility that SIRT4 regulates mammary development by controlling nutrient metabolism in mammary glands (Aim 2). Altered metabolic states in both mice and humans have been shown to inhibit mammary development. For example, both underweight and overweight mice have impaired mammary development that can result in insufficient lactation. Thus, we seek to determine whether the known effects of SIRT4 on nutrient metabolism may contribute to how SIRT4 regulates mammary development. Overall, our proposed studies will reveal a new role for SIRT4 in regulating mammary development. Ultimately, by investigating how SIRT4 influences normal mammary physiology, we may better understand why SIRT4 expression levels are downregulated in breast cancer tissue and whether this contributes to disease progression.


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: 2025 ( Subtotal = $0 )
2025	2023	SAN JOSE STATE UNIVERSITY RESEARCH FOUNDATION	1 WASHINGTON SQ	SAN JOSE	CA	95112	SANTA CLARA	USA	Biomedical Research and Research Training	000	3	6/16/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $146,500 )
2023	2023	SAN JOSE STATE UNIVERSITY RESEARCH FOUNDATION	210 4TH ST 3RD FL	SAN JOSE	CA	95112	SANTA CLARA	USA	Biomedical Research and Research Training	000	3	2/15/2023	NON-COMPETING CONTINUATION	$146,500
														Subtotal = $146,500

Issue Date FY: 2022 ( Subtotal = $146,500 )
2022	2022	SAN JOSE STATE UNIVERSITY RESEARCH FOUNDATION	210 4TH ST 3RD FL	SAN JOSE	CA	95112	SANTA CLARA	USA	Biomedical Research and Research Training	001	2	6/15/2022	NON-COMPETING CONTINUATION	$14,650
2022	2022	SAN JOSE STATE UNIVERSITY RESEARCH FOUNDATION	210 4TH ST 3RD FL	SAN JOSE	CA	95112	SANTA CLARA	USA	Biomedical Research and Research Training	000	2	3/1/2022	NON-COMPETING CONTINUATION	$131,850
														Subtotal = $146,500

Issue Date FY: 2021 ( Subtotal = $146,500 )
2021	2021	SAN JOSE STATE UNIVERSITY RESEARCH FOUNDATION	210 4TH ST 3RD FL	SAN JOSE	CA	95112	SANTA CLARA	USA	Biomedical Research and Research Training	000	1	3/24/2021	NEW	$146,500
														Subtotal = $146,500

Grand Total All Awards = $439,500

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Regulation of Mammary Gland Development by Sirtuin 4

Award Number: SC2GM141997

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: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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