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Tumor Biology & 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

Groot, Marnix de

Marnix de Groot

Technician

Experience

During my masters Biomedical Sciences, I joined a research group in Frankfurt, Germany where I established an in vitro assay to test for cytotoxic immune cell interactions in 3D models of colorectal cancer. This assay could serve as a platform to pre-clinically assess the efficacy of cell-based immune therapy. Being fascinated by the dynamic interplay between immune cells and the tumor micro-environment, I joined the Akkari group to help understanding the role of various subsets of macrophages in the liver and brain tumor microenvironment.

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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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Kloosterman, Daan

Daan Kloosterman

Ph.D. student

Experience

I studied Biology at Leiden University where I specialized in Molecular Genetics and Biotechnology. For my first master internship I joined the lab of Ewa Snaar-Jagalska at Leiden University, where I studied the angiogenic role of innate immune cells during the progression of melanoma. For my second internship I joined the Goessling lab at Harvard Medical School in Boston. In this lab I studied the non-canonical functions of macrophages during intestinal development.

In November 2019, I joined the Akkari group to further explore the complexity and importance of macrophages. My project focusses on elucidating the mechanism behind the rewiring of tumor-associated macrophages by brain tumors in response to therapy.

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Ramirez

Christel Ramirez

Ph.D. student

Experience

After completing my bachelor project at Sanquin and obtaining my Bachelor's degree in Biomedical sciences in 2016 at the University of Amsterdam, I proceeded to do the Master track infection and immunity. My first internship was at the Amsterdam UMC at the center for Experimental and Molecular Medicine  where I focused on differentially expressed genes in sepsis. In 2017 I joined the lab of Dr Leila Akkari at the NKI for my final internship, where I explored the crosstalk between cancer cells and macrophages in the context of liver cancer.

In November 2018, I continued working as a Ph.D student to further explore the potential of immune cell targeting in hepatocellular carcinoma.

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Tessier, Jeremy

Jeremy Tessier

Ph.D. student

Experience

After a bachelor in cellular and molecular biology, I obtained a Master in oncology from the University of Montpellier. As part of this training, I had the opportunity to perform 3 independent  internships of 6 months​​ at the IRCM of Montpellier, the NKI in Amsterdam and the Karolinska institute in Stockholm. This latest internship in Sweden confirmed my growing interest in the role played by the microenvironment in tumor proliferation and treatment resistance. I therefore joined the Akkari group were I work on elucidating the roles of immune cells in recurrent brain tumors emerging post- cytotoxic therapy. 

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Hooren, Luuk van

Luuk van Hooren

Postdoctoral Fellow

Experience

During my master at Maastricht University I did an internship on mucosal immunology in the lab of Dr. Hiroshi Ohno in Yokohama, Japan. In 2013 I moved to Sweden to start my PhD at Uppsala University. Here I studied the tumor vasculature and its role in mediating the response to cancer immunotherapy under supervision of Dr. Anna Dimberg. I also gained an interest in the regulation of immune responses in the brain. In 2019, I started my postdoc in the group of Dr. Leila Akkari, where I will study the immune response to brain tumors during radiotherapy and immunotherapy. 

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Vegna, Serena

Serena Vegna, PhD

Postdoctoral fellow

Experience

I started my research experience in the laboratory of Pr Mauro Piacentini at the University of Rome Tor Vergata, where I performed my M.Sc. degree working in the field of cell death and cancer biology. I then trained in Dr Ula Hibner's laboratory in Montpellier (France) as a PhD fellow, focusing on the interplay between hepatitis C virus replication and host innate immunity in the context of liver carcinogenesis. After short post-doctoral stay in Pr Fabien Zoulim's lab at the Lyon Cancer Research Center (France) working on HBV and the hepatic microenvironment, I joined Dr Leila Akkari's group in September 2017 as a postdoctoral fellow. My project focuses on the role of tumor associated-macrophages in hepatocellular carcinoma development and response to therapy.

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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., Setty M., Leslie C., Oei Y., Pedraza A.,
    Zhang J., Brennan C.W., Sutton J.C., Holland E.C., Daniel D., Joyce J.A.

    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 T., Joyce J.A.

    Link to pubmed
 
 

Recent publications View All Publications

  • Inducing and exploiting vulnerabilities for the treatment of liver cancer.

    Nature. 2019 Oct;574(7777):268-272.

    Wang C, Vegna S, Jin H, Benedict B, Lieftink C, Ramirez C, de Oliveira RL, Morris B, Gadiot J, Wang W, du Chatinier A, Wang L, Gao D, Evers B, Jin G, Xue Z, Schepers A, Jochems F, Sanchez AM, Mainardi S, Te Riele H, Beijersbergen RL, Qin W, Akkari L, Bernards R.

    Link to pubmed
  • Understanding the Origin and Diversity of Macrophages to Tailor Their Targeting in Solid Cancers.

    Front Immunol. 2019 Sep 25;10:2215.

    Kielbassa K, Vegna S, Ramirez C, Akkari L.

    Link to pubmed
 

Contact

  • Office manager

    Karin van der Heijden

  • E-mail

    k.vd.heijden@nki.nl

  • Telephone Number

    0031 20 512 2055

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