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Immunology: Leila Akkari, Ph.D.

Akkari, Leila

Leila Akkari, Ph.D.Junior Group Leader

About Leila Akkari

Macrophage Dynamics in Cancer Treatment

Our group studies the microenvironment-mediated mechanisms of tumor maintenance and therapeutic resistance in brain and liver malignancies. In particular, we investigate the acquired resistance mechanisms resulting from alterations in the activation and recruitment of myeloid cells, more specifically macrophages and their mediators in response to standard of care treatment. Interestingly, we have shown that altering the activity of tumor-associated macrophages (TAMs) in gliomas results in their reeducation into potent anti-tumor effectors. One of our goal is to define the functions of resident versus infiltrating macrophages in protecting tumor cells in the context of combined radio- and chemotherapy, the standard-of-care treatment for glioma. Given that the number of TAMs increases in the context of glioma treatment, we aim to identify the vulnerabilities in the cancer cell/ stromal compartment heterotypic communication that may be targeted therapeutically. Furthermore, we are also interested in understanding how genetic mutations in cancer cells shape the tumor microenvironment to its advantage in hepatocellular carcinoma.

Our research interests involve the use of in vitro and in vivo systems for the study of brain and liver cancer, including high throughput imaging, as well as sophisticated transgenic and cell-tracing mouse models and patients sample analyses.

The ultimate goal of our projects is to improve the understanding of the complexity of the tumor microenvironment to harness its potential, using the brain and liver and experimental settings of cancer inflammation.

Co-workers

Handgraaf

Shanna Handgraaf, MSc

Ph.D. student

Experience

After completing a Bachelor in Human Movement Sciences and a Premaster in Biomedical Sciences, I obtained my Master's degree in Oncology at the VU University in Amsterdam. During this Master, I performed internships at the VUmc/CCA in the department of oncogenetics, as well as at the NYU Medical Center (New York City) in the group of Dr. Michele Pagano.

My PhD thesis in the Akkari lab will focus on elucidating the dynamic roles of innate immune cells in brain tumor resistance and recurrence post-therapy.

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Jules Gadiot, BSc

Technician

Experience

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Key publications View All Publications

  • CSF-1R inhibition alters macrophage polarization and blocks glioma progression.

    Nat Med. 2013 Oct;19(10):1264-72.

    Pyonteck S.M.*, Akkari L.*, Schuhmacher A.J.*, Bowman R.L., Sevenich L., Quail D.F., Olson O.C., Quick M., Huse J., Teijeiro V., et al.

    Link to pubmed
  • Distinct functions of macrophage-derived and cancer cell-derived cathepsin Z combine to promote tumor malignancy via interactions with the extracellular matrix.

    Genes Dev. 2014 Oct 1;28(19):2134-50.

    Akkari L., Gocheva V., Kester J.C., Hunter K.E., Quick M.L., Sevenich L., Wang H.W., Peters C., Tang L.H., Klimstra D.S., Reinheckel et al.

    Link to pubmed
 
 

Recent publications View All Publications

  • An IGF1/IGF1R-PI3K signaling loop underlies acquired resistance to CSF1R inhibition in the glioma microenvironment

    Science. 2016 May 20;352(6288):aad3018.

    Quail D.F., Bowman R.L., Akkari, L. Quick M.L., Schuhmacher, A.J. Huse J.T., Holland E.C., Sutton J.C., Joyce J.A.

    Link to pubmed
  • Combined deletion of cathepsin protease family members reveals compensatory mechanisms in cancer.

    Genes Dev. 2016 Jan 15;30(2):220-32.

    Akkari L., Gocheva V., Quick M.L., Kester J.C., Spencer A.K., Garfall A.L., Joyce J.A.

    Link to pubmed
 

Contact

  • Office manager

    Renske Muns-de Jong

  • E-mail

    rm.d.jong@nki.nl

  • Telephone Number

    0031 20 512 2055

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