# The impact of inflammation on hematopoietic stem cell specification

> **NIH NIH K01** · IOWA STATE UNIVERSITY · 2020 · $150,930

## Abstract

Hematopoietic stem cells (HSCs) are rare cells within human bone marrow that are responsible both for
the life-long replenishment of all blood cell lineages and for the curative effects of bone marrow transplantation.
The creation of human induced pluripotent stem cells holds great promise for cellular regeneration therapies, but
it is not currently possible to instruct these cells to generate HSCs in vitro. The goal of this application is to
determine how pro-inflammatory signaling via NF-kB instructs HSC fate in the vertebrate embryo, and how this
process is regulated by Progranulin a (Pgrna), with the ultimate goal of replicating HSC generation in vitro for
clinical utility. My working hypothesis is that early pro-inflammatory inputs converge to activate NF-kB, which in
turn activates key signaling events in the specification of HSC fate. These pro-inflammatory signals need to be
downregulated soon after HSC specification; my preliminary results suggest that Pgrna functions in this manner.
To test these hypotheses, this proposal consists of 2 aims: (1) Characterize the role of NF-kB in HSC
specification; and (2) identify the role of Pgrna in HSC emergence. This study will be conducted in zebrafish,
which are an ideal system for direct visualization of HSCs and have served as a model organism to study human
disease. To achieve this application’s goals, novel transgenic and mutant lines will be generated, and qPCR,
FACS-sorting, RNA-seq and confocal microscopy techniques will be utilized.
 Dr. Espin Palazon is a postdoctoral fellow in David Traver’s laboratory at UCSD whose ultimate career
goal is to lead an independent research group focused on stem cells at a major research institution. Her short-
term goals are (1) to determine the spatiotemporal requirements of NF-kB within hemogenic endothelium, and
the downstream genes regulated to specify HSCs; and (2) to elucidate how Pgrna governs HSC emergence.
She was recruited to join Dr. Traver’s group because of her strong background in immunology and the zebrafish
animal model. The project outlined in this proposal will allow Dr. Espin Palazon to transition from a mentored
scientific position to an independent research career, helping her gain expertise in FACS sorting, RNA-seq,
genome editing techniques, and HSC biology, all of which are fundamental to establish her independent lab. Dr.
Espin Palazon will meet and present her work to experts in development, immunology and hematology, in
addition to presenting her data to a formal mentorship committee comprised of senior experts that will aid her
transition to an independent researcher. UCSD offers numerous courses that Dr. Espin Palazon will attend, as
well as seminars on career development and laboratory management. The vibrant, collaborative scientific
atmosphere at UCSD is an ideal environment for Dr. Espin Palazon to develop during the mentored phase of
her award, and will be instrumental in forming the foundation for the future success of th...

## Key facts

- **NIH application ID:** 10016274
- **Project number:** 5K01DK115661-04
- **Recipient organization:** IOWA STATE UNIVERSITY
- **Principal Investigator:** Raquel Espin Palazon
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $150,930
- **Award type:** 5
- **Project period:** 2017-09-08 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016274

## Citation

> US National Institutes of Health, RePORTER application 10016274, The impact of inflammation on hematopoietic stem cell specification (5K01DK115661-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10016274. Licensed CC0.

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