SubsidieMeestersNanobodies to prevent hematopoietic stem cell bias and hyper-inflammation.
This project aims to test novel nanobodies that erase inflammatory memories in hematopoietic stem cells to prevent hyper-inflammation and improve therapeutic strategies for age-related disorders.
Projectdetails
Introduction
With a growing ageing population, there is an imminent demand to develop new therapeutic strategies to ameliorate disorders of the hematopoietic system. Our innate immune system can remember its previous encounters with inflammatory triggers.
Epigenetic Memories
Epigenetic memories of previous inflammatory experiences throughout an individual's lifetime are imprinted in hematopoietic stem cells (HSCs), a small pool of bone marrow progenitors that give rise to all our blood cells. Inflammation harms HSCs, causing their functional decline and premature ageing.
Consequences of Inflammation
It also causes long-term differentiation bias and a heightened basal inflammatory status, known as inflammageing. The most striking characteristic of aged HSCs is their increased expression of platelet and megakaryocyte markers and their commitment towards platelet biogenesis, referred to as Platelet-bias.
Impact on Human Health
Platelet bias has important consequences for human health. In our ERC starting grant project PLAT-IL-1 (714175), we discovered that platelets boost the inflammatory capacity of innate immune cells and are essential for the cytokine production of human monocytes. Our findings support that a dangerous combination of myeloid and platelet bias in inflammation-exposed HSCs results in heightened innate immune activation.
Persistent Injuries
The injuries to HSCs are persistent and continue even after the clearance of the inflammatory insult, indicating that remnants of inflammatory events accrue and prolong damage to HSCs. Hence, if we could erase these harmful remnants, we could UNBIAS HSC differentiation and prevent hyper-inflammation.
Project Objectives
In our ERC-funded project, we developed novel nanobodies that efficiently eliminate remnants of inflammation in vivo. In this PoC project, we will test the ability of nanobodies to erase memories from previous inflammatory events and prevent hyper-inflammation.
Future Directions
This project will be a stepping stone to licensing our nanobodies to industrial partners.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 150.000 |
| Totale projectbegroting | € 150.000 |
Tijdlijn
| Startdatum | 1-8-2023 |
| Einddatum | 31-1-2025 |
| Subsidiejaar | 2023 |
Partners & Locaties
Projectpartners
- UNIVERSITATSKLINIKUM BONNpenvoerder
Land(en)
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Vergelijkbare projecten uit andere regelingen
| Project | Regeling | Bedrag | Jaar | Actie |
|---|---|---|---|---|
Network Synergies in Tissue Homeostasis and Stromal Prevention of Inflammatory Disease.This project aims to uncover the mechanisms of tissue homeostasis and stromal biology to prevent inflammation onset, using advanced bioimaging and computational techniques for therapeutic advancements. | ERC STG | € 1.499.514 | 2022 | Details |
What does your blood remember? The memory of hematopoietic stem cells.This project aims to investigate how hematopoietic stem cells develop adaptive memory to environmental stress, enhancing blood cell responses and improving transplantation strategies. | ERC STG | € 2.500.000 | 2022 | Details |
Dissecting the molecular regulation of hematopoietic stem cell emergence using pluripotent stem cells to improve ex vivo therapiesThis project aims to develop methods for generating and expanding hematopoietic stem cells from patient-specific induced pluripotent stem cells to overcome transplantation barriers and enhance therapies. | ERC COG | € 2.000.000 | 2023 | Details |
Origins and Consequences of Hematopoietic Stem Cell MemoriesMemOriStem aims to uncover the origins and mechanisms of hematopoietic stem cell memories to enhance regenerative therapies for chronic inflammation, aging, and cancer. | ERC STG | € 1.500.000 | 2022 | Details |
Network Synergies in Tissue Homeostasis and Stromal Prevention of Inflammatory Disease.
This project aims to uncover the mechanisms of tissue homeostasis and stromal biology to prevent inflammation onset, using advanced bioimaging and computational techniques for therapeutic advancements.
What does your blood remember? The memory of hematopoietic stem cells.
This project aims to investigate how hematopoietic stem cells develop adaptive memory to environmental stress, enhancing blood cell responses and improving transplantation strategies.
Dissecting the molecular regulation of hematopoietic stem cell emergence using pluripotent stem cells to improve ex vivo therapies
This project aims to develop methods for generating and expanding hematopoietic stem cells from patient-specific induced pluripotent stem cells to overcome transplantation barriers and enhance therapies.
Origins and Consequences of Hematopoietic Stem Cell Memories
MemOriStem aims to uncover the origins and mechanisms of hematopoietic stem cell memories to enhance regenerative therapies for chronic inflammation, aging, and cancer.