Leila Akkari trained in cellular and molecular biology during a BA at the University of Montpellier in France, and graduated in 2004 before performing a Master in oncology and immunology between Montpellier and Manchester (England). She performed her PhD in health sciences at the Molecular Genetics Institute of Montpellier, CNRS, in HCV-driven liver cancer prior to joining Prof. Johanna Joyce's laboratory at Memorial Sloan Kettering Cancer Center in NYC as a post doc. During this time, she worked on mouse models of brain and pancreatic cancer, primarily focusing on tumor-associated macrophages and their pro-tumorigenic roles in multiple tumor microenvironment.

Since January 2017, Leila Akkari leads a research group at the Netherlands Cancer Institute in Amsterdam that is interested in the microenvironment-mediated mechanisms of tumor maintenance and therapeutic resistance to therapy in brain and liver malignancies. The main focus of her research is to understand and target the dynamic changes in the tumor microenvironment that are associated with cancer malignancy, with a particular interest in macrophages, a highly plastic and heterogenous immune cell type in solid cancers. Her lab uses a plethora of murine models of cancers to develop and test microenvironment- targeted drugs in a stage-dependent and population-dependent manner.

• 2020-2024: EMBO Young Investigator Program Awardee

• 2020-2024: Vidi Research Grant. NWO (Life Sciences Netherlands)

• 2019-2023: Selected as Junior Member of the Oncode Institute (NL)

• 2017-2022: Young Investigator Grant, Bas Mulder Award. KWF (Dutch Cancer Society)

• 2017-2022: Cancer Genomics Center, Young Investigator Program. NWO, NL

• 2014- 2016 Post-doctoral fellowship grant, American Brain Tumor Association

• 2012-2014 Brain Tumor Center post-doc fellowship, MSKCC, New York City

1. Wang C. ^#, Vegna S. ^#, Jin H. ^#, Benedict B. ^#, Lieftink C., Ramirez C., de Oliveira R.L., Morris B., Gadiot J., Wang W., du Chatinier A., Wang L., Gao D., Evers B., Jin G., Xue Z., Schepers A., Jochems F., Sanchez A.M., Mainardi S., Te Riele H., Beijersbergen R.L., Qin W.*, Akkari L.^*, Bernards R.^*. # co-first authors; *co-corresponding authors.Nature 2019, Oct;574 (7777):268-272.

2. Kielbassa K.^#, Vegna S.^#, Ramirez C., Akkari L.^*. Understanding the Origin and Diversity of Macrophages to Tailor Their Targeting in Solid Cancers. Front Immunol, 2019 Sep 25;10:2215.

3. Taranto D, Ramirez CFA, Vegna S, de Groot MHP, de Wit N, Van Baalen M, Klarenbeek S, Akkari L. Curr Protoc. 2021 Jun;1(6):e147. doi: 10.1002/cpz1.147. Multiparametric Analyses of Hepatocellular Carcinoma Somatic Mouse Models and their Associated Tumor Microenvironment.

4. Jin H, Shi Y, Lv Y, Yuan S, Ramirez CFA, Lieftink C, Wang L, Wang S, Wang C, Dias MH, Jochems F, Yang Y, Bosma A, Hijmans EM, de Groot MHP, Vegna S, Cui D, Zhou Y, Ling J, Wang H, Guo Y, Zheng X, Isima N, Wu H, Sun C, Beijersbergen RL, Akkari L, Zhou W, Zhai B, Qin W, Bernards R. Nature 2021, Jul;595(7869):730-734. EGFR Activation Limits the response of liver cancer to Lenvatinib.

5. Akkari L.*, Bowman R.L., Tessier J., Klemm F., Handgraaf S.M., de Groot M., Quail D.F., Tillard L., Gadiot J., Huse J.T., Brandsma D., Westerga J., Watts C., Joyce J.A..*. Sci Transl Med. 2020 Jul 15;12(552). *co-corresponding authors. Dynamic Changes in Glioma Macrophage Populations after Radiotherapy reveal CSF-1R inhibition as a Stategy to Overcome Resistance.

6. 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. 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.

7. 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. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013 Oct;19(10):1264-72. *co-first authors.

8. Akkari L.*, Gocheva V. *, Quick M.L., Kester J.C., Spencer A.K., Garfall A.L., Joyce J.A. Combined deletion of cathepsin protease family members reveals compensatory mechanisms in cancer. Genes Dev. 2016 Jan 15;30(2):220-32.

9. 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. An IGF1/IGF1R-PI3K signaling loop underlies acquired resistance to CSF1R inhibition in the glioma microenvironment (2016). Science. 2016 May 20;352(6288):aad3018

10. Erbani J, Boon M, Akkari L. Therapy-induced shaping of the tumor microenvironment: Macrophages at play. Seminar in Cancer Biology.doi: 10.1016/j.semcancer.2022.05.003.

11. Li MO, Wolf N, Raulet DH, Akkari L, Pittet MJ, Rodriguez PC, Kaplan RN, Munitz A, Zhang Z, Cheng S, Bhardwaj N. Cancer Cell 2021. Jun 14;39(6):725-729. Innate Immune Cells in the Tumor Microenvironement