Krista Heinonen

Areas of expertise

Hematopoiesis and stem cells , Emergency myelopoiesis , Infection-adapted hematopoiesis

  • INRS Professor

Phone
450-687-5010, extension 4408

Fax
450-686-5501

Email
krista.heinonen@iaf.inrs.ca

Armand-Frappier Santé Biotechnologie Research Centre

531 blvd. des Prairies
Laval, Quebec  H7V 1B7
Canada

See research centre

Interested research topics

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.

Publications

HAMMAMI, A., ABIDIN, B. M., HEINONEN, K. M. & STAGER, S. (2018)
HIF-1α hampers dendritic cell function and Th1 generation during chronic visceral leishmaniasis,
Scientific Reports, 8, 1, 3500.

 

KWARTENG, E. O., HETU-ARBOUR, R. & HEINONEN, K. M. (2018)
Wnt/β-catenin pathway promotes early engraftment of fetal hematopoietic stem/progenitor cells,
Journal of Leukocyte Biology, 103, 3, 381-393.

 

HAMMAMI, A., ABIDIN, B. M., FABIE, A., CHARPENTIER, T., DUGUAY, A.-P., HEINONEN, K. M. & STAGER, S. (2017)
Hif-1α is a key regulator in potentiating suppressor activity and limiting the microbicidal capacity of MDSC-like cells during visceral leishmaniasis,
PLoS Pathogens, 13, 9, e1006616.

 

ABIDIN, B. M., HAMMAMI, A., STAGER, S. & HEINONEN, K. M. (2017)
Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis,
PLoS Pathogens, 13, 8, e1006422.

 

KWARTENG, E. O. & HEINONEN, K. M. (2016)
Competitive transplants to evaluate hematopoietic stem cell fitness,
Journal of Visualized Experiments, 144, e54345.

 

ABIDIN, B. M., KWARTENG, E. O. & HEINONEN, K. M. (2015)
Frizzled-6 regulates hematopoietic stem/progenitor cell survival and self-renewal,
Journal of Immunology, 195, 5, 2168-2176.

 

PRUNSKAITE-HYYRYLÄINEN, R., SHAN, J., RAILO, A., HEINONEN, K. M., MIINALAINEN, I., YAN, W., SHEN, B., PERREAULT, C. & VAINIO, S. J. (2014)
Wnt4, a pleiotropic signal for controlling cell polarity, basement membrane integrity, and antimüllerian hormone expression during oocyte maturation in the female follicle,
FASEB Journal, 28, 4, 1568-1581.

 

HEINONEN, K. M., VANEGAS, J. R., LEW, D., KROSL, J. & PERREAULT, C. (2011)
Wnt4 enhances murine hematopoietic progenitor cell expansion through a planar cell polarity-like pathway,
PLoS ONE, 6, 4, e19279.

 

HEINONEN, K. M., VANEGAS, J. R., BROCHU, S., SHAN, J., VAINIO, S. J. & PERREAULT, C. (2011)
Wnt4 regulates thymic cellularity through the expansion of thymic epithelial cells and early thymic progenitors,
Blood, 118, 19, 5163-73.

 

GIROUX, M., DELISLE, J. S., GAUTHIER, S. D., HEINONEN, K. M., HINSINGER, J., HOUDE, B., GABOURY, L., BROCHU, S., WU, J., HEBERT, M. J. & PERREAULT, C. (2011)
SMAD3 prevents graft-versus-host disease by restraining Th1 differentiation and granulocyte-mediated tissue damage,
Blood, 117, 5, 1734-44.

 

HEINONEN, K. M., BOURDEAU, A., DOODY, K. M. & TREMBLAY, M. L. (2009)
Protein tyrosine phosphatases PTP-1B and TC-PTP play nonredundant roles in macrophage development and IFN-gamma signaling,
Proceedings of the National Academy of Sciences of the United States of America, 106, 23, 9368-72.

 

LOUIS, I., HEINONEN, K. M., CHAGRAOUI, J., VAINIO, S., SAUVAGEAU, G. & PERREAULT, C. (2008)
The signaling protein Wnt4 enhances thymopoiesis and expands multipotent hematopoietic progenitors through beta-catenin-independent signaling,
Immunity, 29, 1, 57-67.

 

HEINONEN, K. M. & PERREAULT, C. (2008)
Development and functional properties of thymic and extrathymic T lymphocytes,
Critical Reviews in Immunology, 28, 5, 441-66.

 

BOURDEAU, A., DUBE, N., HEINONEN, K. M., THEBERGE, J. F., DOODY, K. M. & TREMBLAY, M. L. (2007)
TC-PTP-deficient bone marrow stromal cells fail to support normal B lymphopoiesis due to abnormal secretion of interferon-{gamma},
Blood, 109, 10, 4220-8.

 

HEINONEN, K. M. & TREMBLAY, M. L. (2006)
Protein tyrosine phosphatase 1B in hematopoiesis,
Cell Cycle, 5, 10, 1053-6.

 

HEINONEN, K. M., DUBE, N., BOURDEAU, A., LAPP, W. S. & TREMBLAY, M. L. (2006)
Protein tyrosine phosphatase 1B negatively regulates macrophage development through CSF-1 signaling,
Proceedings of the National Academy of Sciences of the United States of America, 103, 8, 2776-81.

 

DUBE, N., BOURDEAU, A., HEINONEN, K. M., CHENG, A., LOY, A. L. & TREMBLAY, M. L. (2005)
Genetic ablation of protein tyrosine phosphatase 1B accelerates lymphomagenesis of p53-null mice through the regulation of B-cell development,
Cancer Research, 65, 21, 10088-95.

 

HEINONEN, K. M., NESTEL, F. P., NEWELL, E. W., CHARETTE, G., SEEMAYER, T. A., TREMBLAY, M. L. & LAPP, W. S. (2004)
T-cell protein tyrosine phosphatase deletion results in progressive systemic inflammatory disease,
Blood, 103, 9, 3457-64.