Institute of Molecular Genetics of the Czech Academy of Sciences
Supervisor
Meritxell Alberich Jordà
Project description
Hematopoietic stem and progenitor cells (HSPCs) are responsible for lifelong maintenance of the blood system, yet their function progressively declines with age. Chronic inflammation, a hallmark of aging, represents a major and persistent stressor that reshapes HSPC transcriptional and metabolic programs. Rather than promoting adaptive immune responses, long-term inflammatory signaling drives cumulative damage, leading to loss of stem cell fitness, skewed differentiation, and reduced regenerative capacity.
Emerging evidence, including our recent work, indicates that chronic inflammatory exposure accelerates aging-associated deterioration of HSPCs and promotes the emergence of pre-leukemic states. This project aims to identify the molecular mechanisms that normally protect HSPCs from sustained inflammatory stress and to determine how these safeguarding programs fail during aging and chronic inflammation. A central objective is to define transcriptional and metabolic alterations that predispose HSPCs to clonal expansion and malignant transformation under chronic inflammation.
Using in vitro systems and murine models of aging and chronic inflammation, we will perform integrated transcriptomic and metabolic analyses to dissect these processes. In addition, we will explore strategies to restore HSPC function by targeting inflammation-induced vulnerabilities. This work will provide mechanistic insight into how aging-associated inflammation contributes to hematopoietic decline and pre-leukemic evolution, with potential relevance for early intervention strategies.
Candidate profile
The laboratory of hemato-oncology is searching for a highly motivated, enthusiastic and hard-working Ph.D. student. The candidate should hold a master degree in genetics, molecular biology, cell biology, or in a related field. Bioinformatic skills or basic knowledge of large dataset analysis will be positively evaluated. The candidate should be willing to work with murine models. Excellent English is required. The candidate should be a team-player and willing to work with other lab members and international collaborators.
We offer a friendly and supporting environment in a state-of-the-art institution.
Suggested reading
Supervisor
Meritxell Alberich Jordà
Project description
Hematopoietic stem and progenitor cells (HSPCs) constitute a rare yet indispensable population within the bone marrow that sustains lifelong blood cell production. Preservation of their integrity and functional capacity is essential for normal hematopoiesis, as perturbations in this compartment can result in bone marrow failure syndromes and leukemic transformation.
Recent work from our group has revealed that acute infections are sensed not only by mature immune cells but also directly by HSPCs, positioning these cells as active participants in early immune responses. Building on these findings, this project aims to elucidate how HSPCs contribute to infection control while simultaneously undergoing transcriptional and metabolic adaptations that safeguard their long-term functionality.
To address these questions, we will combine in vitro culture systems with in vivo murine models of infection, complemented by transcriptomic and metabolic profiling approaches. This integrative strategy will allow us to dissect the molecular mechanisms that enable HSPCs to balance immune responsiveness with self-preservation. Ultimately, this work will provide fundamental insights into HSPC biology under inflammatory stress and may reveal mechanisms relevant to infection-driven hematopoietic dysfunction and leukemogenesis.
Candidate profile
The laboratory of hemato-oncology is searching for a highly motivated, enthusiastic and hard-working Ph.D. student. The candidate should hold a master degree in genetics, molecular biology, cell biology, or in a related field. Bioinformatic skills or basic knowledge of large dataset analysis will be positively evaluated. The candidate should be willing to work with murine models. Excellent English is required. The candidate should be a team-player and willing to work with other lab members and international collaborators.
We offer a friendly and supporting environment in a state-of-the-art institution.
Suggested reading
