# Unexpected roles of phosphoinositides in the nucleus

> **NIH NIH R35** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $364,490

## Abstract

PROJECT SUMMARY / ABSTRACT
Phosphoinositides (PIs) are a minor class of phospholipids often comprising less than 1% of the cellular lipid
cohort. Despite the low abundance, PIs have huge impacts on cell physiology and alterations of PI signaling
pathways are associated with the pathogenesis of many human diseases including neurodegenerative diseases,
metabolic disorders, autoimmunity, and cancer. This pathophysiological importance is largely due to the
signaling roles of PIs which depend on the subcellular distribution of PIs and on key interactions between PIs
and PI effectors. A twist in PI signaling is that in contrast to general belief, a substantial fraction of PIs is found
in non-membranous nuclear compartments. The nature and functions of nuclear PIs remains largely unknown
due to the lack of systematic studies of nuclear PIs and PI effectors. We have expertise in defining and
characterizing novel PI effector proteins involved in key signaling pathways including vesicular trafficking,
cytoskeleton dynamics, and transcription regulation. Since PI kinases are often associated with PI effectors thus
ensuring PI generation is spatiotemporally linked to PI effector activation, we have performed proteomic analyses
to identify the interactomes of the nuclear PI-generating kinases. Out of these proteomic screens, we have
validated several nuclear complexes that associate with nuclear PI kinases or with PIs themselves. The validated
complexes include transcription factors and coactivators, epigenetic enzymes and associated corepressors, the
DNA repair machinery, and factors involved in RNA processing. We recently discovered that nuclear PIs
accumulate at distinct subnuclear regions such as nuclear speckles and DNA double-strand breaks. Based on
our novel discoveries of PIs and PI kinases interacting with effectors in the nucleus, the overarching goal of
my research program is to decipher the signaling pathways emanating from the nuclear PIs. Our overall
hypothesis is that upon suitable stimuli the activation of nuclear PI kinase at specific subnuclear compartments
elevates the local concentration of nuclear PIs and these nuclear PI foci function as platforms to regulate PI
effectors recruited to the foci mediating transcription regulation and assembly of complexes that regulate
epigenetic changes. The goals of my research programs for the next five years include dissecting the nature and
subnuclear distribution of nuclear PIs using novel microscopic tools which will enable us to obtain high resolution
images of the nuclear PIs, defining the new roles of PIs regulating chromatin positioning to nuclear speckles,
and investigating novel roles of nuclear PIs in regulating gene expression with focuses on transcription regulation
and epigenetic repression with innovative cell biological, genome-wide, and biochemical approaches. Upon the
completion of the research programs, we will obtain insight into the unexpected roles and molecular mechanism
of PIs in...

## Key facts

- **NIH application ID:** 10897258
- **Project number:** 5R35GM150504-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Suyong Choi
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $364,490
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10897258

## Citation

> US National Institutes of Health, RePORTER application 10897258, Unexpected roles of phosphoinositides in the nucleus (5R35GM150504-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10897258. Licensed CC0.

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