# The role of Rpl5 haploinsufficiency in hematopoietic stem/progenitor cell function in Diamond Blackfan anemia > **NIH NIH K08** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $171,060 ## Abstract PROJECT SUMMARY/ABSTRACT Anemia is an extraordinarily common condition that affects approximately 1 in 3 people around the globe. Erythropoiesis is exquisitely sensitive to both endogenous and exogenous stress, which contributes to this massive global disease burden. Genetic defects in ribosomes that lead to severe anemia are associated with rare inherited bone marrow failure syndromes as well as more commonly acquired myelodysplastic syndrome. The pathway from ribosomal protein haploinsufficiency to defective erythropoiesis in Diamond Blackfan anemia (DBA) is complex and likely involves multiple factors (e.g. diminished GATA1 translation, heme toxicity and/or nucleolar stress). Patients with DBA can undergo spontaneous remission such that chronic transfusions are not required. This phenomenon is poorly understood using current patient registries and animal models. Understanding normal pathways that lead to the resolution or improvement of anemia is critical in order to advance therapies for DBA and other causes of anemia. The applicant is a pediatric hematologist/oncologist who actively treats patients with all types of genetic and acquired anemias and her long term goal is to become a physician-scientist with expertise in hematopoiesis. To achieve this goal, the candidate has proposed the following training plan: 1) To develop expertise in isolation and analysis of hematopoietic stem/progenitor cells; 2) To further develop expertise employing mouse models and human hematopoietic stem cell culture to study disease-specific mechanisms; 3) To develop an independently funded basic research laboratory; 4) To develop into a successful physician-scientist focused on mentorship and collaboration. The candidate has assembled a mentorship team with expertise in hematopoiesis and mouse models (Drs. Engel and Li). The environment at the University of Michigan is highly conducive to the training of successful junior physician-scientists with exceptional resources, educational and collaborative opportunities. The scientific proposal centers on the hypothesis that DBA remission, even in these inbred mice, is based on a threshold effect on hematopoietic stem/progenitor cells that responds to both exogenous and endogenous modifiers. The rationale for this hypothesis is based on observations in our unique DBA mouse model where all neonatal Rpl5 (ribosomal protein gene) mutant mice are born with anemia, which contributes to early mortality in some mice while others survive and maintain normal hemoglobin characteristics throughout their lifespan. Aim 1 will determine if there is an intrinsic defect in stem/progenitor cells and/or the bone marrow microenvironment in mutant mice by examining transplantation of hematopoietic cells from different developmental periods. Aim 2 will test whether cellular stress alters the niche and/or hematopoietic stem/progenitor cell function. Aim 3 will examine whether cell cycle dysregulation is responsible for defective hematopoiesi... ## Key facts - **NIH application ID:** 10368461 - **Project number:** 1K08DK127013-01A1 - **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR - **Principal Investigator:** Sharon A Singh - **Activity code:** K08 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2022 - **Award amount:** $171,060 - **Award type:** 1 - **Project period:** 2022-03-01 → 2027-02-28 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10368461 ## Citation > US National Institutes of Health, RePORTER application 10368461, The role of Rpl5 haploinsufficiency in hematopoietic stem/progenitor cell function in Diamond Blackfan anemia (1K08DK127013-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10368461. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*