# Decoding innate immune signaling in normal and myelodysplastic hematopoiesis

> **NIH NIH R35** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $788,750

## Abstract

Abstract
Research in my laboratory has made critical findings related to the molecular, cellular, and
genetic basis of Myelodysplastic Syndromes (MDS), a complex and poorly understood
hematopoietic stem cell (HSC) failure syndrome. The complexity and heterogeneity of MDS, and
the lack of mouse models, remain as major obstacles to understanding and effectively treating
this disease. A major focus of my lab has been the intersection of immune biology and MDS.
Namely, we have uncovered and characterized genetically-driven aberrant activation of the Toll-
like receptor (TLR) (i.e., innate immune) pathway in MDS HSC, and now have evidence that
TLR signaling is a major unifying driver of MDS pathogenesis. While dissecting the role of TLR
signaling in MDS HSC, we identified a critical function of TLR signaling in normal HSC, a finding
that has broader implications in chronic immune-related disorders and hematopoietic processes.
As such, my research program has developed transformative and innovative approaches to
investigate the intersection of TLR signaling, hematopoiesis, and MDS, which serve as the
foundation for this proposal: (i) to dissect the genetic, molecular, and cellular underpinnings of
MDS, with an emphasis on genetically-driven activation of TLR signaling (Research Focus 1);
(ii) to evaluate the developmental requirement of the TLR signaling hub, TRAF6, in normal HSC
function and MDS (Research Focus 2); and, (iii) to use the knowledge gained by our basic
research to identify and develop novel therapeutic modalities for the treatment of MDS
(Research Focus 3). The proposed research will impact our understanding of the initiation,
progression, and treatment of MDS.

## Key facts

- **NIH application ID:** 9851435
- **Project number:** 5R35HL135787-04
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Daniel Starczynowski
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $788,750
- **Award type:** 5
- **Project period:** 2017-01-10 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851435

## Citation

> US National Institutes of Health, RePORTER application 9851435, Decoding innate immune signaling in normal and myelodysplastic hematopoiesis (5R35HL135787-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851435. Licensed CC0.

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