Overview

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

Grusanovic S, Danek P, Kuzmina M, Adamcova MK, Burocziova M, Mikyskova R, Vanickova K, Kosanovic S, Pokorna J, Reinis M, Brdicka T, Alberich-Jorda M: Chronic inflammation decreases HSC fitness by activating the druggable Jak/Stat3 signaling pathway. EMBO Rep 2022 e54729.
Burocziova M, Grusanovic S, Vanickova K, Kosanovic S, Alberich-Jorda M: Chronic Inflammation Promotes Cancer Progression as a Second hit. Exp Hematol 2023.
Pavliuchenko N, Kuzmina M, Danek P, Spoutil F, Prochazka J, Skopcova T, Pokorna J, Sedlacek R, Jorda MA, Brdicka T: Genetic background affects neutrophil activity and determines the severity of autoinflammatory osteomyelitis in mice. J Leukoc Biol 2024.
Vanickova K, Milosevic M, Ribeiro Bas I, Burocziova M, Yokota A, Danek P, Grusanovic S, Chiliński M, Plewczynski D, Rohlena J, Hirai H, Rohlenova K, Alberich-Jorda M: Hematopoietic stem cells undergo a lymphoid to myeloid switch in early stages of emergency granulopoiesis. EMBO J 2023 e113527.
Danek P, Kardosova M, Janeckova L, Karkoulia E, Vanickova K, Fabisik M, Lozano Asencio C, Benoukraf T, Tirado-Magallanes R, Zhou Q, Burocziova M, Rahmatova S, Pytlik R, Brdicka T, Tenen DG, Korinek V, Alberich Jorda M: β-catenin-TCF/LEF signaling promotes steady-state and emergency granulopoiesis via G-CSF receptor upregulation. Blood 2020.

APPLY HERE: https://www.img.cas.cz/phd