# Red Cell Membrane Studies

> **NIH NIH P01** · NEW YORK BLOOD CENTER · 2021 · $1,269,424

## Abstract

Overall Project Abstract
Anemia is a major health problem affecting millions of individuals around the world. The overall
objective of the proposed program is to develop an improved mechanistic understanding of
erythropoiesis, with the goal of defining pathophysiological mechanisms resulting in anemia due to
ineffective erythropoiesis. Our overarching hypothesis is that normal human erythropoiesis requires
major changes in patterns of gene expression that impact key interconnected pathways in
mitosis/cytokinesis, apoptosis, metabolite transport and nuclear structure. Comparisons of these
pathways will be performed in a number of important red cell disorders. Four independent but
complementary projects that rely on each other have been assembled to explore different aspects of
human erythropoiesis. Project 1 will develop a comprehensive mechanistic understanding of the role of
changes in gene expression in generating distinct erythroid populations with particular focus on the
regulation of erythroid progenitors and late stages of terminal erythroid differentiation including
enucleation in normal and disordered erythropoiesis. Project 2 will develop a mechanistic
understanding of how the ordered synthesis of distinct proteins is regulated during erythropoiesis by
identifying and characterizing enhancers regulating stage-specific programs of gene expression in
highly specialized human erythroid cells. In parallel, proteins undergoing mRNA translation at different
stages of erythroid development and differentiation will be defined and characterized by ribosomal
profiling. Project 3 will develop a mechanistic understanding of the role of cell metabolism in erythroid
differentiation. The role of cytokines in erythroid differentiation has been extensively studied but it is
only recently that we have begun to recognize the importance of nutrient entry and metabolism in
transitioning to different erythroid stages and the proposed project will use a novel scaffold of ligands to
metabolite transporters in order to extend our fundamental knowledge of metabolism in erythroid
differentiation. These data will reveal novel pathways by which metabolites regulate erythroid lineage
differentiation and will result in the identification, and potential manipulation of nutrient transporters that
orient erythroid progenitor survival and differentiation in physiological erythropoiesis as well as in the
disordered erythropoiesis. Project 4 will develop mechanistic understanding of the role of cell and
nuclear stiffness and polarized contractile forces in enucleation, marrow egress, and `self' recognition
by macrophages of erythroid cells. The role of lamins, the main nuclear structural proteins in cells, in
regulating nuclear rigidity and of myosin-driven cell polarization in these processes will be explored.
These insights will result in improved mechanistic understanding of key cellular event during erythroid
differentiation.

## Key facts

- **NIH application ID:** 10228568
- **Project number:** 5P01DK032094-33
- **Recipient organization:** NEW YORK BLOOD CENTER
- **Principal Investigator:** Mohandas Narla
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,269,424
- **Award type:** 5
- **Project period:** 1997-01-30 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228568

## Citation

> US National Institutes of Health, RePORTER application 10228568, Red Cell Membrane Studies (5P01DK032094-33). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10228568. Licensed CC0.

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