# Regulating proliferation and differentiation of erythroid progenitors

> **NIH NIH K08** · DANA-FARBER CANCER INST · 2020 · $166,740

## Abstract

PROJECT SUMMARY / ABSTRACT
Diamond-Blackfan anemia (DBA) is a unique example of a bone marrow failure disorder that improves with drug
treatment. Glucocorticoids increase red blood cell production in most DBA patients, but the underlying
mechanism of clinical efficacy was unclear until recently. I identified a phenomenon where mouse burst forming
unit-erythroid (BFU-E) cells progress through a continuum of developmental states during transit-amplification;
glucocorticoid treatment decreases the degree of developmental progression per cell cycle, resulting in a greater
number of transit-amplifying cell divisions before the onset of erythroid terminal differentiation (Developmental
Cell, 2019). Conversely, TGFβ treatment of BFU-Es increases rate of developmental progression and decreases
overall BFU-E proliferative capacity. My findings defined a novel developmental biology paradigm where rate of
progenitor cell developmental progression regulates balance of proliferation and differentiation, and total cellular
output. Insights into the mechanisms by which glucocorticoids and TGFβ regulate proliferative capacity remain
elusive, and the conclusions from my mouse erythropoiesis studies must be directly tested in human
erythropoiesis. I will identify the target genes of glucocorticoid and TGFβ signaling in BFU-Es using nascent
transcriptome profiling and chromatin occupancy and architecture profiling. Furthermore, I will use single cell
RNA sequencing of normal and DBA patient bone marrow hematopoietic progenitor cells to compare
glucocorticoid and TGFβ effects on mouse erythropoiesis and human erythropoiesis. My proposed studies will:
(i) contribute broadly to our understanding of pathophysiology and treatment principles in bone marrow failure,
(ii) further develop a novel field within developmental biology that arose from my earlier postdoctoral work, and
(iii) provide ample opportunities for mechanistic and translational follow-up for my transition to independence.
I am a physician-scientist seeking K08 support for mentored research under the guidance of Dr. Harvey Lodish
and Dr. Stuart Orkin. This mentored period of 80% research and career development, and 20% clinical time, will
ensure I acquire the skills required to become a successful independent principal investigator. Drs. Lodish and
Orkin are internationally recognized mentors, together training >200 successful independent investigators; both
received the American Society of Hematology Basic Science Mentor Award. My training will occur at two world-
class institutions, the Whitehead Institute for Biomedical Research, and the Dana-Farber/Boston Children's
Cancer and Blood Disorders Center. Both are rich with opportunities for young scientists to train, pursue highly
impactful science, and foster long-lasting collaborations. I will also be guided by a committee of researchers that
are all leaders in their fields: Drs. David Bartel (RNA biology), Peter Reddien (developmental biology), and Akik...

## Key facts

- **NIH application ID:** 9871171
- **Project number:** 1K08DK123414-01
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Hojun Li
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $166,740
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9871171

## Citation

> US National Institutes of Health, RePORTER application 9871171, Regulating proliferation and differentiation of erythroid progenitors (1K08DK123414-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9871171. Licensed CC0.

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