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Krista Heinonen

Stem cells and hematopoiesis

Emergency myelopoiesis, infection-adapted hematopoiesis, leukemia

 

Research interests

 

All cells of the adult immune system are derived from a small number of bone marrow hematopoietic stem cells (HSC). In addition to being able to develop into the different blood cell lineages, HSC also have the unique capacity to self-renew. The number of HSCs is tightly regulated and unbalanced proliferation and differentiation can lead to multiple immune-related illnesses, such as inflammatory diseases, autoimmunity, immune deficiency and cancer (leukemias and lymphomas).

 

HSC interaction with the bone marrow microenvironment is necessary for their self-renewal. These interactions are often altered in the case of leukemias, for example. On the other hand, one of the technical challenges in the field is to develop methods for stem cell expansion in culture while limiting the loss of their self-renewal capacity. Our research projects can be divided in three main themes:

 

1) The role of Wnt/Frizzled signaling in the interactions of HSC with the bone marrow stroma (NSERC)

 

Wnt-planar cell polarity (Wnt-PCP) pathway is best known for its role in maintaining spatial organization in epithelial tissues. These membrane proteins are also expressed in HSCs, and we hypothesize that they could regulate HSC interaction with bone marrow stroma and thus influence HSC polarity, cell division symmetry, and self-renewal. The ultimate goal of these projects is to identify new targets with the potential to amplify HSCs in culture or in situ in the bone marrow.

 

2) The role of HSCs and emergency myelopoiesis in chronic infections (CIHR)

A proper immune response relies to a great extent on efficient immune cell differentiation. This is particularly true for innate responses, as innate cells generally have relatively short half-lives and depend on constant replenishment from the bone marrow. An acute, systemic infection induces HSC activation in the bone marrow, generating an influx of myeloid cells, such as neutrophils, monocytes and dendritic cells. Depending on the type of response required for pathogen clearance, this emergency response can be either beneficial or detrimental to the host. We have shown that a persistent infection by the parasite Leishmania donovani (visceral leishmaniasis) induces a massive activation of HSCs and emergency myeloid progenitor cells, leading to an increase in inflammatory monocytes. These monocytes are more permissive to infection by Leishmania, and their accumulation thus promotes parasite replication. Our on-going work aims at better understanding the underlying mechanisms and applying these findings to other chronic infections.

 

3) The impact of Wnt signaling on the development of immune-related pathologies, such as myeloid leukemias.

 

Current projects

 

Please send your cv (with contact information for two references), a copy of transcripts and a brief letter of motivation by email.

 

Biography

 

Dr. Heinonen completed her Ph.D. at McGill University in 2006. After a postdoctoral fellowship at the Institute for Research in Immunology and Cancer (IRIC), she joined Institut Armand Frappier in November 2011.

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