Thursday, July 3, 2025 7/3/2025

Expression, Regulation and Function of the SULT1C Carcinogen-Activating Enzymes

Award Number: R01ES022606
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/08/2014
PERIOD OF PERFORMANCE END DATE: 12/31/2025

Group Awards By:

View Award Description

Expression, Regulation and Function of the SULT1C Carcinogen-Activating Enzymes - The cytosolic sulfotransferase (SULT) conjugating enzymes have the dual ability to metabolize endogenous compounds and xenobiotics, with consequences that include enhanced drug elimination, prodrug activation, hormone inactivation, and pro-carcinogen bioactivation. Unlike most other classes of xenobiotic-metabolizing enzymes, several SULTs are prominently expressed during prenatal life, implying that these enzymes perform important physiological functions in the developing human. Also, although the maternal liver and placenta protect the fetus against xenobiotic exposures, many xenobiotics can cross the placental barrier, making the SULTs especially important determinants of the impact of xenobiotic exposures on developmental processes. Our research group has shed new light on the hepatic expression patterns of the SULTs during human development. For example, we were the first to show that human estrogen sulfotransferase (SULT1E1), a major estrogen-inactivating enzyme, is robustly expressed in liver during gestation and substantially down- regulated after birth. However, the mechanisms that control the temporal expression of SULT1E1 and other prenatally-expressed SULTs, such as SULT1C2, are unknown. Also, the substrate specificities and enzymatic mechanisms of some SULTs are not adequately defined. In the proposed project, we will determine the mechanisms that control SULT1C2 and 1E1 expression during human liver development and will characterize in detail the enzymology of SULT1C2, one of the least studied of the SULTs, in order to understand its function in the developing human. We hypothesize that expression of the SULT1C2 and 1E1 genes is first upregulated and subsequently downregulated during human hepatocyte differentiation through the concerted action of a network of liver-enriched transcription factors, additional differentiation-associated transcription factors, and coregulators. We further hypothesize that the major substrates of SULT1C2 include endogenous molecules that are abundant during prenatal life as well as multiple classes of xenobiotics, and that substrate selectivity and catalytic activity are markedly influenced by structural rearrangements that are induced by binding of the SULT co-factor 3'-phosphoadenosine-5'-phosphosulfate. The specific aims of this project are to: (1) define the region(s) of the SULT1C2 and 1E1 genes that control their transcription in models of human hepatocyte differentiation; (2) identify the transcription factors and coregulators that control SULT1C2 and 1E1 transcription in models of human hepatocyte differentiation and in human liver specimens; and (3) characterize the structure-function activity of human SULT1C2. This project will increase our fundamental knowledge about the mechanisms that control endogenous and foreign chemical metabolism during human development, uncover new information about the function of a major SULT that is expressed during prenatal life, and provide new insight into the types of environmental exposures that could dysregulate SULT expression and function during this most vulnerable period of life.


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 = $610,104 )
2025	2025	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	10	12/17/2024	NON-COMPETING CONTINUATION	$610,104
														Subtotal = $610,104

Issue Date FY: 2024 ( Subtotal = $610,104 )
2024	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	9	1/29/2024	NON-COMPETING CONTINUATION	$610,104
														Subtotal = $610,104

Issue Date FY: 2023 ( Subtotal = $623,997 )
2023	2023	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	8	12/23/2022	NON-COMPETING CONTINUATION	$623,997
														Subtotal = $623,997

Issue Date FY: 2022 ( Subtotal = $487,888 )
2022	2022	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	7	2/10/2022	NON-COMPETING CONTINUATION	$487,888
														Subtotal = $487,888

Issue Date FY: 2021 ( Subtotal = $501,388 )
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	6	3/15/2021	COMPETING CONTINUATION	$501,388
														Subtotal = $501,388

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	5	3/14/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $388,865 )
2018	2018	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	5	10/31/2017	NON-COMPETING CONTINUATION	$388,865
														Subtotal = $388,865

Issue Date FY: 2017 ( Subtotal = $388,865 )
2017	2017	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	4	10/29/2016	NON-COMPETING CONTINUATION	$388,865
														Subtotal = $388,865

Issue Date FY: 2016 ( Subtotal = $388,865 )
2016	2016	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	3	11/12/2015	NON-COMPETING CONTINUATION	$388,865
														Subtotal = $388,865

Issue Date FY: 2015 ( Subtotal = $388,865 )
2015	2015	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Environmental Health	001	2	1/28/2015	NON-COMPETING CONTINUATION	$38,886
2015	2015	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	2	11/3/2014	NON-COMPETING CONTINUATION	$349,979
														Subtotal = $388,865

Issue Date FY: 2014 ( Subtotal = $414,674 )
2014	2014	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	1	1/8/2014	NEW	$414,674
														Subtotal = $414,674

Grand Total All Awards = $4,803,615

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Expression, Regulation and Function of the SULT1C Carcinogen-Activating Enzymes

Award Number: R01ES022606

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/08/2014

PERIOD OF PERFORMANCE END DATE: 12/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer