# NF-kB signaling in the control of Hematopoiesis

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $386,250

## Abstract

Project Summary:
NF-κB signaling pathway is one of the most extensively studied and understood
pathways, however, the physiological impact of augmented NF-κB signaling in
hematopoiesis has not been understood. Despite many recent studies documenting
constitutive activation of NF-κB in patients with hematological disorders, including AML
and MDS, it is remains unclear if constitutive NF-κB signaling is sufficient and/or
necessary for the onset of the disease. Recently, we have shown that lack of A20 (a
negative regulator of NF-κB) in hematopoietic stem cells (HSCs) causes loss of
quiescence and severe hematologic abnormalities, due to constitutive NF-κB activation.
In an attempt to decipher the role of NF-κB in HSCs, directly , we engineered mice to
constitutively activate NF-κB in HSCs. Our preliminary data indicate that HSC
quiescence and pool were completely lost, and that increased NF-κB signal alone was
sufficient to disturb the transcriptional regulatory circuits of HSCs. In the proposed
research, we would like to decode the potential molecular mechanisms through which
increased NF-κB signals affect HSC biology.
Our hypothesis is that deregulated canonical NF-κB signals impair hematopoietic
stem cell (HSC) quiescence and functions by altering signal transduction
pathways, `transcription factor networks' and expression of pro-inflammatory
cytokines. To test this hypothesis, we will use a combination of genetic, molecular cell
biology and biochemical approaches. In specific aim 1, we will decipher the intrinsic
mechanisms through which NF-κB affects HSC functions. In specific aim 2, we will
unravel the extrinsic role of NF-κB in the control of HSCs. In specific aim 3, we would
generate a novel humanized mouse model and decode the involvement of NF-κB
signals in human HSC biology.
 We believe that the proposed research will provide key insights into the
pathologic processes involving deregulated NF-κB signals, and will aid the development
of newer and more successful therapies for human hematologic diseases that arise due
to constitutive NF-κB activation.

## Key facts

- **NIH application ID:** 9859433
- **Project number:** 5R01HL132194-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Chozha Vendan Rathinam
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,250
- **Award type:** 5
- **Project period:** 2017-02-15 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859433

## Citation

> US National Institutes of Health, RePORTER application 9859433, NF-kB signaling in the control of Hematopoiesis (5R01HL132194-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9859433. Licensed CC0.

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