Research Group Nina Cabezas-Wallscheid

Keywords

Hematopoietic stem cells, metabolism, ageing, leukemia, dietary interventions

Summary & Mission statement

1. My laboratory focuses on understanding the epigenetic and metabolic regulation of hematopoietic stem cell dormancy in health, ageing and upon malignant transformation.
2. We aim to develop innovative therapeutic strategies targeting hematological malignancies.

Overview

Aging is associated with deregulated cellular metabolism and increased incidence of acute myeloid leukemia (AML). Clonal hematopoiesis, an aging-related phenomenon common in elderly people, represents a hallmark link between aging and AML. Deregulated metabolism was shown to contribute to the pathogenesis and progression of AML and to protect AML leukemic stem cells (LSCs) from chemotherapy-induced damage. Our research focus on understanding how hematopoietic stem cell (HSC) dormancy is epigenetically and metabolically regulated upon ageing and leukemia progression. To this end, we have established low input methods to measure the transcriptome, metabolome and epigenome of rare cell populations.  These methods development led to the discovery of a non-classical vitamin A/retinoic acid (RA) signaling axis that regulates HSC self-renewal. In a follow up pre-clinical study, we showed that supplementation with 4-oxo-RA dampens HSC activation following myocardial infarction, reducing inflammation and improving cardiac repair. Moreover, we created the first metabolic atlas of human bone marrow HSCs, revealing age-related metabolic dysfunctions and significant alterations in leukemia, such as decreased choline levels, which can be reversed through choline supplementation. These discoveries shed light on the metabolic vulnerabilities of HSCs in both aging and leukemia contexts. Now our laboratory aims to explore novel targeted metabolic interventions to preserve HSC function upon aging and combat leukemia progression in patients.

Legend: The figure illustrates the regulation of hematopoietic stem cell dormancy (night) through dietary factors (metabolism/nutrients). These components play a crucial role in modulating HSC quiescence and activation.