Thursday, October 30, 2025 10/30/2025

Discordant transcriptional regulation of gluconeogenic and lipogenic gene expression

Award Number: R01DK110063
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2016
PERIOD OF PERFORMANCE END DATE: 06/30/2026

Group Awards By:

View Award Description

Discordant transcriptional regulation of gluconeogenic and lipogenic gene expression - Abstract Dysregulated glucose and lipid metabolism are hallmarks of insulin resistance and type 2 diabetes. In the liver, this is manifested as the inability of insulin to suppress hepatic glucose output, while de novo lipogenesis remains elevated even in the fasted state but is still capable of displaying an insulin-stimulated increase. The inability of insulin to suppress hepatic glucose output while activating de novo lipogenesis has been referred to as selective insulin resistance. The acute regulation of both gluconeogenesis and de novo lipogenesis primarily results from rapid changes in allosteric regulation, however, in chronic states such as insulin resistance and type 2 diabetes there are marked changes in gluconeogenic and lipogenic gene expression. We have obtained preliminary data indicating that the prototypical lipogenic genes (i.e. FASN, SCD1) are primarily regulated by transcription initiation whereas gluconeogenic genes (i.e.: PCK1, G6Pc) are primarily regulated at the level of transcriptional elongation. During diet induced hepatic insulin resistance, the elongation factor Spt5 is functionally dysregulated thereby increasing gluconeogenic gene expression in the fed state. In addition, using single cell RNAseq we have identified the differential engagement of different hepatocyte subsets during the fasting/feeding cycle that are also altered during the development of hepatocyte insulin resistance. Based upon these data, we propose two specific aims to examine several novel molecular and cellular mechanisms that are important regulatory components of normal physiologic hepatocyte lipogenic and gluconeogenic gene expression that are subsequently dysregulated during diet-induced insulin resistance. Specifically, we use 1) ChIP-Seq to determine the changes in various initiation and elongation factors in their DNA occupancy binding, 2) ATAC-Seq to determine chromatin organization, and 3) ChRO-Seq to directly measure the rates of transcription across gene bodies. These analyses of total hepatocyte function will be complemented with single cell molecular analyses that include 1) single cell RNA-Seq to directly determine differential function of hepatocyte subsets, 2) single cell ATAC-Seq for individual hepatocyte chromatin organization changes, and 3) single molecule FISH to assess individual cellular transcriptional activity and identification of their anatomical zonation. These approaches will allow us to determine the molecular mechanisms responsible for the activation of transcriptional initiation and elongation between lipogenic and gluconeogenic gene expression, and will expand our understanding of the individual hepatocyte cellular responses that account for these changes in under normal fasting/feeding states and in diet-induced liver insulin resistance.


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 = $598,996 )
2025	2025	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	7/31/2025	NON-COMPETING CONTINUATION	$598,996
														Subtotal = $598,996

Issue Date FY: 2024 ( Subtotal = $575,035 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	6/24/2024	NON-COMPETING CONTINUATION	$575,035
														Subtotal = $575,035

Issue Date FY: 2023 ( Subtotal = $598,996 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	6/29/2023	NON-COMPETING CONTINUATION	$598,996
														Subtotal = $598,996

Issue Date FY: 2022 ( Subtotal = $598,996 )
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	8	7/14/2022	NON-COMPETING CONTINUATION	$598,996
2022	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	11/20/2021	COMPETING CONTINUATION	$3
2022	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	11/20/2021	NON-COMPETING CONTINUATION	-$3
														Subtotal = $598,996

Issue Date FY: 2021 ( Subtotal = $598,996 )
2021	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	7/15/2021	COMPETING CONTINUATION	$598,996
2021	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	7/7/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $598,996

Issue Date FY: 2020 ( Subtotal = $594,253 )
2020	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	4/24/2020	NON-COMPETING CONTINUATION	$594,253
														Subtotal = $594,253

Issue Date FY: 2019 ( Subtotal = $594,253 )
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	007	5	4/30/2019	NON-COMPETING CONTINUATION	$594,253
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	4	2/11/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$140,500
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	006	4	3/28/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$37,091
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	2/8/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$140,500
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	4	2/12/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$140,500
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	005	3	3/28/2019	NON-COMPETING CONTINUATION	-$37,091
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	3	3/14/2019	NON-COMPETING CONTINUATION	$0
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	2/8/2019	NON-COMPETING CONTINUATION	-$140,500
														Subtotal = $594,253

Issue Date FY: 2018 ( Subtotal = $594,253 )
2018	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/31/2018	NON-COMPETING CONTINUATION	$594,253
														Subtotal = $594,253

Issue Date FY: 2017 ( Subtotal = $594,253 )
2017	2017	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	3/28/2017	NON-COMPETING CONTINUATION	$534,827
2017	2017	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	6/13/2017	NON-COMPETING CONTINUATION	$59,426
														Subtotal = $594,253

Issue Date FY: 2016 ( Subtotal = $594,253 )
2016	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/10/2016	NEW	$594,253
														Subtotal = $594,253

Grand Total All Awards = $5,942,284

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Discordant transcriptional regulation of gluconeogenic and lipogenic gene expression

Award Number: R01DK110063

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/15/2016

PERIOD OF PERFORMANCE END DATE: 06/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer