Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Structure and function of phospholipids and inositol phosphates in the nucleus.

Award Number: R35GM156389
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: 05/05/2025
PERIOD OF PERFORMANCE END DATE: 02/28/2030

Group Awards By:

View Award Description

Structure and function of phospholipids and inositol phosphates in the nucleus. - Summary: Phospholipids and inositol phosphates are two classes of small molecules with well-known functions in the cytoplasm, but poorly defined roles in the nucleus. The goal of my diverse group is to understand the structural biology and functional genomics of these two classes of small molecules. We also take chemical biology approaches to develop new small molecules to interrogate nuclear functions, which informs therapeutic development for several human diseases. Nuclear lipids are enigmatic molecules because they are found outside membranes, within the nucleoplasm and have metabolic and signaling properties distinct from membrane lipids. However, we do not understand fundamental aspects of the structure or function of nuclear lipids, which are ubiquitous, well conserved signaling molecules. Funding over the past 3.5 years has used the NR5A nuclear phospholipid receptors as models to address these questions. Those studies informed new approaches to small molecule screening for full-length NR5A2, the results of those screens revealed new molecules that regulate these receptors in new ways, which we build on here. Over the next five years, our studies will reveal the structures of ceramide, sphingomyelin and sphingolipid bound NR5A receptors, as well as new small molecules and genes that regulate nuclear lipid signaling through NR5As, enabling further progress. Nuclear inositol phosphates are soluble signaling molecules made by the nuclear kinase “inositol polyphosphate multikinase”, or IPMK. Work from several groups has established IPMK kinase activity regulates gene expression, however specific cellular mechanisms have remained unclear. Funding over the past 3.5 years used genetics in human cells to show IPMK-generated inositol phosphates specifically activate HDAC3 to regulate histone acetylation, further progress has been hampered by limitations inherent to these genetic knockout/complementation approaches. To overcome this, we helped develop the first selective chemical inhibitors of IPMK, which have revealed novel aspects of inositol phosphate signaling. Over the next five years, we can now use these inhibitors to ask questions not previously possible, defining how IPMK regulates transcription. Our group is uniquely positioned to address these diverse problems because we focus on two model systems: the NR5A nuclear phospholipid receptors and IPMK. We have developed novel chemical and genetic tools that give us unique ability to interrogate these difficult questions. Our work will reveal how phospholipids and inositol phosphates control gene expression, with potential to impact cancer, diabetes and the metabolic side effects of anti-psychotic drugs.


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 = $656,250 )
2026	2026	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Biomedical Research and Research Training	000	2	2/18/2026	NON-COMPETING CONTINUATION	$656,250
														Subtotal = $656,250

Issue Date FY: 2025 ( Subtotal = $778,444 )
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Biomedical Research and Research Training	000	1	5/2/2025	NEW	$778,444
														Subtotal = $778,444

Grand Total All Awards = $1,434,694

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Structure and function of phospholipids and inositol phosphates in the nucleus.

Award Number: R35GM156389

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: 05/05/2025

PERIOD OF PERFORMANCE END DATE: 02/28/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer