# Targeting the ARHGAP25 pathway in acute myelogenous leukemia stem cells

> **NIH NIH K08** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2021 · $169,560

## Abstract

Project Summary/Abstract
Research: Acute myeloid leukemia (AML) has a high relapse rate and is very difficult to cure, in
large part due to the persistence of quiescent, chemotherapy-resistant leukemia stem cells
(LSCs). Successful eradication of LSCs would greatly improve AML cure rates, but specific
targeting of LSCs has been difficult to achieve because LSCs are rare and difficult to study. This
proposal builds on my novel preliminary data indicating that the Rac-GAP Arhgap25 is required
for leukemic transformation of HSCs. To understand more fully the requirement for and
mechanisms underpinning the role of Arhgap25 AML leukemogenesis, I propose three distinct
and complementary lines of investigation in this application, all of which target LSC survival and
maintenance. First, I will fully characterize the cell-of-origin-specific nature of the requirement for
Arhgap25 in leukemogenesis in multiple models of AML. Second, I will identify the
phosphorylation events that permit or prohibit the ability of Arhgap25 to contribute to
leukemogenesis. Finally, I will dissect the biochemical mechanisms responsible for Arhgap25
requirement in the maintenance and survival of AML LSCs. These studies will lay the
groundwork for developing clinically useful combination therapies for AML and, ultimately,
improving AML cure rates.
Environment: The Dana-Farber Cancer Institute (DFCI), Boston Children’s Hospital (BCH), and
the Joslin Diabetes Center at Harvard University are internationally recognized research
programs with a number of world-renowned researchers in the areas of stem cell biology,
hematopoiesis, and cancer biology. The Division of Pediatric Hematology/Oncology/Stem Cell
Transplantation at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, in
particular, has a long and distinguished record of training successful physician-scientists. I have
assembled an excellent mentoring and advisory committee, consisting of Dr. Amy Wagers, Dr.
David Williams, Dr. Leonard Zon, Dr. Kimberly Stegmaier, and Dr. Yi Zheng, who will guide me
through my research and training experiences. Dr. Zheng, who has joined my advisory
committee for this resubmission, is one of the world’s experts in small GTPase biochemistry,
and will aid significantly in providing essential additional training in Rac biochemical techniques
and strategies.
Candidate Career Goals: My long-term career objective is to compete successfully for R01
funding as a tenure-track, independent physician-scientist in a pediatric
hematology/oncology/stem cell transplantation department. A K08 award will provide the senior
mentorship and expertise needed to advance my training, develop my proficiency in new
techniques, and develop my mastery of new concepts. It will also provide critically important
protected time so that I can develop my ideas and projects and bring them to publication in
support of further NIH grant submissions. This research proposal is part of a structured plan
with scient...

## Key facts

- **NIH application ID:** 10177875
- **Project number:** 5K08CA201591-05
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Leo D. Wang
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $169,560
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177875

## Citation

> US National Institutes of Health, RePORTER application 10177875, Targeting the ARHGAP25 pathway in acute myelogenous leukemia stem cells (5K08CA201591-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10177875. Licensed CC0.

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