# Molecular characterization of biliverdin IXbeta reductase

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $483,137

## Abstract

Project Summary/Abstract 
Research proposed in this grant application builds on extensive genetic, biochemical and animal studies
designed to further characterize and validate biliverdin IXβ reductase (BLVRB) as a novel cellular target
regulating human platelet production in situations of stress hematopoiesis, with concomitant effects on
erythroid development and repopulation. Although heme degradation is largely studied as a processing
pathway designed to clear pro-oxidant (free) heme generated during cellular senescence (or metabolism),
heme catabolic enzymes are also known to maintain function(s) in cellular signaling and cytoprotection, and
tetrapyrrole byproducts biliverdin (BV) and bilirubin (BR) function in redox reactions as potent buffer(s) against
oxidant stress. We now challenge existing dogma, hypothesizing that redox-regulated activity involving heme
catabolism functions in a unique metabolic pathway controlling hematopoietic lineage fate with divergent
effects on erythroid/megakaryocyte balance. Research goals are accomplished through two synergistic
specific aims, designed to (1) delineate cellular mechanisms of BLVRB-regulated Mk/Erythroid redox coupling
and cytoprotection in vitro, and (2) define and expand upon mechanisms of lineage-restricted speciation and
cytoprotection in vivo, collectively designed to dissect Blvrb-regulated perturbed pathways controlling E/Meg
lineage speciation from MEPs during stress hematopoiesis. Basic science implications are broadly relevant to
(1) metabolic and bioenergetic consequences of hematopoiesis, (2) heme-regulated redox chemistry, and (3)
novel cellular target validation. Clinical/translational implications are designed to enhance our understanding
of mechanisms of disease pertaining to stem cell metabolism, aging, anemia and platelet production. Unique
reagents and cell lines generated and characterized include (1) murine models of Blvrb- and Blvra-deficiency,
(2) iPSC models with targeted BLVRB knock-outs, (3) biliverdin IXβ (and IXγ, IXδ) isomer detection and
production methodologies. All proposed studies are formulated on pre-existing studies in subject cohorts, and
proposed experiments are predicated on reagents and expertise currently available or in advanced
development among the research team.

## Key facts

- **NIH application ID:** 10815695
- **Project number:** 5R01HL153144-04
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Wadie F Bahou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $483,137
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10815695

## Citation

> US National Institutes of Health, RePORTER application 10815695, Molecular characterization of biliverdin IXbeta reductase (5R01HL153144-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10815695. Licensed CC0.

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