NKI

Daniel Peeper is the Head of the Department of Molecular Oncology & Immunology and chairs both the Scientific Faculty Council and the Translational Research Board at the Netherlands Cancer Institute (NKI). He holds a professorship in Functional Oncogenomics at the VU University Medical Center (VUmc) and was elected as member of Oncode (a funded network of elected scientists in fundamental oncology from across the Netherlands).

Peeper studied Medical Biology at the VU University and received his PhD in the laboratory of Alex van der Eb at the University of Leiden (1994), for his work on adenoviral oncoproteins and cell cycle proteins. He received his postdoctoral training in the laboratories of Mark Ewen (Dana-Farber Cancer Institute, Harvard Medical School, Boston) and René Bernards (NKI). In 2002, Peeper became Assistant Professor and three years later Associate Professor at NKI. Also in that year, he was elected as an EMBO Young Investigator.

In 2002 and 2006, he received NWO VIDI and VICI awards, respectively for his functional oncogenomic studies. In 2007, he received the first KWF Queen Wilhelmina Award, by her Majesty the Queen Beatrix and the minister of Education, for his work on melanoma in collaboration with W. Mooi. In the same year, he received the Society for Melanoma Research Jr. Researcher Award. In 2008, Peeper was appointed affiliate Professor at the VUmc and was elected as EMBO member. In 2013, he received, together with colleagues including A Berns and M Stratton (Sanger Inst.), an ERC Synergy grant (€15 million) for the development of combinatorial cancer therapy. In 2015, he received the Outstanding research award by the Society for Melanoma Research and in 2016 he was elected to become a member of Academia Europaea. In 2017, he was invited to join Oncode.

Peeper has been a member of the European Association for Cancer Research (EACR) Board since 2013, and he also serves on the EACR Conference committee.

Highlights of the Peeper lab include their discoveries that a genomic screen for anoikis resistance can be used to identify metastasis genes (Nature 2004); that Oncogene-Induced cellular Senescence (OIS) serves as a potent in vivo tumor suppressor mechanism limiting cancer progression (Nature 2005; New Engl J Med 2006); the identification of several OIS-associated oncogenes (Nat Cell Biol 2005; Nat Rev Cancer 2006); that OIS is associated with the activation of an inflammatory transcriptome (Cell 2008; Nat Rev Cancer 2009; Genes Dev 2010); the identification of a novel candidate melanoma suppressor gene (EMBO J, 2011) and of a key mechanism of human melanomagenesis involving abrogation of OIS by reduction of PTEN expression (Genes Dev 2012). His laboratory also identified a prognostic breast cancer genetic signature and a factor essential to drive metastasis (PNAS 2013) and discovered that pyruvate dehydrogenase kinase (PDK1) acts as a critical switch for the execution of OIS and serves as an attractive drug target in melanoma (Nature 2013). Peeper and his team demonstrated the power of in vivo shRNA dropout screens for drug target identification (Cell Rep. 2014, Oncotarget 2016) and discovered a new mechanism mediating broad resistance to targeted therapy in melanoma (Nature Commun 2014). They also identified multiple resistance mechanisms to BRAF targeted therapy in a melanoma patient (EMBO Mol Med 2015) and developed a new bioinformatic tool to determine copy number alterations in cancer (Genome Biol 2015).

In addition, they established a large melanoma PDX platform that they used to identify a novel resistance mechanism of melanoma to BRAF inhibition (Cell Rep. 2016), and identified a prognostic genetic network driving human breast cancer (Oncotarget, 2017). Recently, they dissected the mechanism of cancer drug addiction and provided PoC of how this vulnerability may be used clinically (Nature 2017). Most recently, his lab developed a new concept for rational treatment combination: in collaboration with the biotech company Genmab it was demonstrated that melanoma intratumor heterogeneity is effectively targeted by a combination of an AXL-ADC (antibody-drug conjugate) and BRAF pathway inhibitors. By attacking distinct tumor subpopulations, these treatments act in a cooperative fashion, ensuring more durable responses (Nature Medicine 2018).

• 2016: Elected Member of Academia Europaea

• 2015: Society for Melanoma Research (SMR) Outstanding Researcher Award

• 2009: Queen Wilhelmina Award by the Netherlands Cancer Society

• 2008: Elected EMBO Member

• 2007: Society for Melanoma Research (SMR) Jr. Researcher Award

• 2006: VICI Award by the Netherlands Organisation for Scientific Research (NWO)

• 2005: Elected EMBO Young Investigator (YIP)

1. Boshuizen, J., Koopman, L. A., Krijgsman, O., Shahrabi, A., Gresnigt–van den Heuvel, E., Ligtenberg, M. A., ... & Pencheva, N. (2018). Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug conjugate and BRAF/MEK inhibitors. Nature medicine.

2. Kong, X., Kuilman, T., Shahrabi, A., Boshuizen, J., Kemper, K., Song, J. Y., ... & Peeper, D. S. (2017). Cancer drug addiction is relayed by an ERK2-dependent phenotype switch. Nature, 550(7675), 270.

3. Kaplon, J., Zheng, L., Meissl, K., Chaneton, B., Selivanov, V. A., Mackay, G., ... & Gottlieb, E. (2013). A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature, 498(7452), 109.

4. Kuilman, T., Michaloglou, C., Vredeveld, L. C., Douma, S., van Doorn, R., Desmet, C. J., ... & Peeper, D. S. (2008). Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell, 133(6), 1019-1031.

5. Michaloglou, C., Vredeveld, L. C., Soengas, M. S., Denoyelle, C., Kuilman, T., Van Der Horst, C. M., ... & Peeper, D. S. (2005). BRAF E600-associated senescence-like cell cycle arrest of human naevi. Nature, 436(7051), 720.

Tineke Lenstra received her Bachelor's' and Master's' degree in biomedical sciences from Utrecht University (cum laude). In 2008, she joined the laboratory of Frank Holstege at University Medical Centre Utrecht, where she used genome-wide expression analysis to study transcription regulatory complexes. She was awarded a cum laude PhD in 2012. As a postdoc in laboratory of Dan Larson at the National Cancer Institute in Bethesda, USA, she used cutting-edge single-molecule techniques to study transcription dynamics in single cells. In 2016, she established an independent group at the Netherlands Cancer Institute (NKI) in Amsterdam, where her lab applies and further develops single-molecule imaging techniques in living cells to understand the regulatory mechanisms and dynamics of stochastic transcription in eukaryotic cells.

For her work, Tineke has received a number of awards, including the KNAW early career award, the NVBMB prize, the Fellows Award for Research Excellence, the NCI Director's Innovation Award and the “Cancer Genomics and Developmental Biology” PhD Student Award. Her research was supported by the NWO VIDI, NWO-XL, ERC starting grant, CancerGenomics.nl, EMBO long-term fellowships, KWF fellowship for basic research, the NWO Toptalent Program and Huygens Scholarship Talent Program.

• 2023: EMBO young investigator programme (European Molecular Biology Organization)

• 2022: NWO-XL

• 2022: NWO VIDI

• 2020: KNAW early career award (Royal Netherlands Academy of Arts and Sciences)

• 2018: NVBMB prize (Netherlands Organization for Biochemistry and Molecular Biology)

• 2017: ERC starting grant

• 2017: CancerGenomiCs.nl gravitation project

• 2015: NCI Director's Innovation Award

• 2015: Fellows Award for Research Excellence

• 2012: KWF (Dutch Cancer Society) fellowship for basic research

• 2012: European Molecular Biology Organization (EMBO) long-term fellowship

• 2011: “Cancer Genomics and Developmental Biology” PhD Student Award, Utrecht University

• 2008: NWO Toptalent Program

• 2007: Huygens Scholarship Program

1. Brouwer I, Kerklingh E, van Leeuwen F, Lenstra TL. Dynamic epistasis analysis reveals how chromatin remodeling regulates transcriptional bursting. In press at Nature Structural and Molecular Biology. bioRxiv 2021.12.15.472793; doi: https://doi.org/10.1101/2021.12.15.472793.

2. Patel HP, Coppola S, Pomp W, Brouwer I, Lenstra TL. DNA supercoiling restricts the transcriptional bursting of neighboring eukaryotic genes. bioRxiv 2022.03.04.482969v1; doi: https://doi.org/10.1101/2022.0...

3. Donovan BT, Huynh A, Ball DA, Patel HP, Poirier MG, Larson DR, Ferguson ML*, Lenstra TL*. Live-cell imaging reveals the interplay between transcription factors, nucleosomes, and bursting. EMBO Journal. 2019 Jun 17;38(12). PMID: 31101674 *These authors contributed equally

4. de JongeWJ, Patel HP, Meeussen JVW, Lenstra TL. Following the tracks: how transcription factor binding dynamics control transcription. Biophysical Journal. 2022 May 3;121(9):1583-1592. doi: 10.1016/j.bpj.2022.03.026. Epub 2022 Mar 23.

5. Brouwer I, Lenstra TL. Visualizing transcription: key to understanding gene expression dynamics. Current Opinion in Chemical Biology. 2019 Aug;51:122-129. PMID: 31284216

6. Lenstra TL, Coulon A, Chow CC, Larson DR. Single-molecule imaging reveals a switch between spurious and functional ncRNA transcription. Molecular Cell. 2015 Nov 19;60(4):597-610. PMID: 26549684.

7. Lenstra TL, Benschop JJ, Kim T, Schulze JM, Brabers NA, Margaritis T, van de Pasch LA, van Heesch SA, Brok MO, Groot Koerkamp MJ, Ko CW, van Leenen D, Sameith K, van Hooff SR, Lijnzaad P, Kemmeren P, Hentrich T, Kobor MS, Buratowski S, Holstege FCP. The specificity and topology of chromatin interaction pathways in yeast. Molecular Cell. 2011 May 20;42(4):536-49. PMID: 21596317.

Jos Jonkers performed his PhD research (on retroviral insertional mutagenesis screens to identify oncogenes involved in lymphoma progression) in the group of Anton Berns at the NKI. In 1996 he became a postdoc in the Berns lab, where he developed GEMMs of BRCA1/2-associated breast cancer. In 2002, he joined the lab of Allan Bradley at the Wellcome Trust Sanger Institute to develop platforms for DNA copy number analysis of mouse tumors. He became a junior group leader at the NKI in 2003; was appointed as permanent staff member in 2008; and became Head of the Division of Molecular Pathology in 2012.

Major breakthroughs were:

1. development of GEMMs of ILC and BRCA1/2-associated breast cancer

2. identification of multiple mechanisms of therapy resistance in BRCA1-deficient breast cancer

3. development of functional assays for classification of BRCA1 variants of unknown clinical significance

4. development of CRISPR/Cas9-based non-germline GEMMs of breast cancer

• 2018: Awarded the Stand Up To Cancer (SU2C) Laura Ziskin Prize In Translational Cancer Research

• 2017: Awarded Cancer Research UK (CRUK) Grand Challenge grant

• 2014: NWO VICI grant

• 2013: ERC Synergy Grant

• 2012: EMBO membership

• 2002: NWO Genomics Fellowship

• 2002: NWO VIDI grant

1. Annunziato, S., Kas, S. M., Nethe, M., Yücel, H., Del Bravo, J., Pritchard, C., ... & Schut, E. (2016). Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland. Genes & development, 30(12), 1470-1480.

2. Bouwman, P., Aly, A., Escandell, J. M., Pieterse, M., Bartkova, J., van der Gulden, H., ... & Haffty, B. G. (2010). 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nature Structural and Molecular Biology, 17(6), 688.

3. Bouwman, P., van der Gulden, H., van der Heijden, I., Drost, R., Klijn, C. N., Prasetyanti, P., ... & Jonkers, J. (2013). A high-throughput functional complementation assay for classification of BRCA1 missense variants. Cancer discovery, 3(10), 1142-1155.

4. Drost, R., Bouwman, P., Rottenberg, S., Boon, U., Schut, E., Klarenbeek, S., ... & Pieterse, M. (2011). BRCA1 RING function is essential for tumor suppression but dispensable for therapy resistance. Cancer cell, 20(6), 797-809.

5. Jaspers, J. E., Kersbergen, A., Boon, U., Sol, W., van Deemter, L., Zander, S. A., ... & Doroshow, J. H. (2013). Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors. Cancer discovery, 3(1), 68-81.

6. Kas, S. M., de Ruiter, J. R., Schipper, K., Annunziato, S., Schut, E., Klarenbeek, S., ... & Adams, D. J. (2017). Insertional mutagenesis identifies drivers of a novel oncogenic pathway in invasive lobular breast carcinoma. Nature genetics, 49(8), 1219.

Thijn Brummelkamp received his Msc in biology from the Free University in Amsterdam, in 1998. He did his graduate research at The Netherlands Cancer Institute in the laboratory of René Bernards and received his PhD cum laude from Utrecht University in 2003. After his PhD he was appointed as group leader (Whitehead Fellow) at the Whitehead Institute for Biomedical Research in Cambridge, USA. In 2011 his laboratory moved to the Netherlands Cancer Institute in Amsterdam and he became adjunct PI at Center for Molecular Medicine (CeMM) in Vienna. Thijn has co-founded the biotech companies Haplogen GmbH (Vienna) and Scenic Biotech (Amsterdam).

He developed and applied technologies for genetics in cultured human cells (shRNA libraries and genetics in haploid mammalian cells) that are widely used in biomedical research. He identified a new class of intracellular receptors for highly pathogenic Ebola and Lassa viruses, studied the principles of synthetic lethal interactions in human cells, identified genes needed for glycosylation of alpha-dystroglycan and mutated in Walker-Warburg syndrome and assigned a function to the cylindromatosis tumor suppressor gene.

• 2015: Ammodo Award, Dutch Academy of Sciences (KNAW)

• 2013: EMBO Gold Medal

• 2012: Phoenix Pharmazie Wissenschaftspreis

• 2012: The Molecular Biosystems Early Career Award

• 2006: Kimmel Scholar Award, Sidney Kimmel Foundation for Cancer Research

• 2005: TR35: Elected as one of the world’s top young innovators by Technology Review Magazine

• 2004: NVBMB Award (Dutch association for biochemistry and molecular biology)

• 2003: Antoni Van Leeuwenhoek Award, for contributions on Functional Genomics

1. Blomen, V. A., Májek, P., Jae, L. T., Bigenzahn, J. W., Nieuwenhuis, J., Staring, J., ... & Marceau, C. (2015). Gene essentiality and synthetic lethality in haploid human cells. Science, 350(6264), 1092-1096.

2. Brockmann, M., Blomen, V. A., Nieuwenhuis, J., Stickel, E., Raaben, M., Bleijerveld, O. B., ... & Brummelkamp, T. R. (2017). Genetic wiring maps of single-cell protein states reveal an off-switch for GPCR signalling. Nature, 546(7657), 307.

3. Carette, J. E., Raaben, M., Wong, A. C., Herbert, A. S., Obernosterer, G., Mulherkar, N., ... & Dal Cin, P. (2011). Ebola virus entry requires the cholesterol transporter Niemann–Pick C1. Nature, 477(7364), 340.

4. Nieuwenhuis, J., Adamopoulos, A., Bleijerveld, O. B., Mazouzi, A., Stickel, E., Celie, P., ... & Brummelkamp, T. R. (2017). Vasohibins encode tubulin detyrosinating activity. Science, eaao5676.

5. Staring, J., von Castelmur, E., Blomen, V. A., van den Hengel, L. G., Brockmann, M., Baggen, J., ... & Perrakis, A. (2017). PLA2G16 represents a switch between entry and clearance of Picornaviridae. Nature, 541(7637), 412.

René Bernards studied adenovirus transformation for his PhD research with Alex van der Eb in Leiden. He joined the laboratory of Robert Weinberg at the Whitehead Institute in Cambridge, USA for his postdoctoral training. He was appointed assistant professor at the Massachusetts General Hospital Cancer Center in 1988. In 1992 he joined the Netherlands Cancer Institute in Amsterdam. In 1994 he was also appointed part time professor of molecular carcinogenesis at Utrecht University, The Netherlands.

During his PhD research, he showed that the difference between oncogenic and non-oncogenic adenoviruses was primarily due to their differential ability to switch off the expression of MHC class I antigens, allowing evasion of T cell immune responses. During his postdoctoral work, he showed that downregulation of MHC class I antigens is also a property of the MYCN oncoprotein and, in collaboration with Stephen Friend, isolated the first tumor suppressor gene, RB1.

After returning to Amsterdam in 1992, his major scientific accomplishments include the development of MammaPrint, the first molecular diagnostic test for personalized treatment of breast cancer that has been used clinically since 2004 to select patients for adjuvant therapy. Recently, MammaPrint was validated in a large phase III clinical study, which demonstrated that over 250,000 women in the EU and US that are treated with chemotherapy annually can safely forego this toxic treatment without loss of survival benefit.

His laboratory also developed the first shRNA vector for gene silencing in mammalian cells and used this vector to create the first genome-scale library of shRNA vectors, enabling genome-wide loss of function genetic screens in mammalian cells. His laboratory has used this vector collection to identify the PI3K pathway as a major determinant of resistance to herceptin in breast cancer and to identify the CYLD tumor suppressor gene as a regulator of NF-kB signaling, which suggested a strategy to treat cylindromatosis. His laboratory also used genetic screens to identify a number of particularly powerful drug combinations for the treatment of cancer, based on the concept of synthetic lethality. This work identified the combination of a BRAF inhibitor and an EGFR inhibitor as effective for the treatment of BRAF mutant colon cancer, a combination that was FDA and EMA approved in 2020. There are currently multiple clinical trials ongoing that test the efficacy of the combination therapies suggested by genetic screens from his laboratory.

He has co-founded four companies: Prolifix (developed belinostat for treatment of peripheral T cell lymphoma), Agendia (developed MammaPrint for breast cancer diagnosis), Qameleon Therapeutics (Qamelostat for treatment of BRAF inhibitor-resistant melanoma) and Oncosence (pro senescence therapy for cancer).

• 2022: Princess Takamatsu Memorial Lectureship, AACR.

• 2020: International member, National Academy of Sciences (USA).

• 2019: International Honorary Member, American Academy of Arts and Sciences.

• 2018: Fellow of the AACR Academy, class of 2018.

• 2013: Academy Professor Prize, Royal Netherlands Academy of Arts and Sciences.

• 2012: Queen Wilhelmina Research Prize, Dutch Cancer Society.

• 2011: Scrip Best Partnership Alliance Award for colorectal cancer collaboration with AstraZeneca and Agendia.

• 2009: Fellow, European Academy of Cancer Sciences.

• 2007: ESMO Lifetime Achievement Award in Translational Research in Breast Cancer.

• 2007: Member, Royal Netherlands Academy of Arts and Sciences

• 2005: Ernst W. Bertner Award for Cancer Research, M.D. Anderson Cancer Center.

• 2005: Spinoza award, Netherlands Organization for Scientific Research.

• 2005: Member, Academia Europea.

• 2005: Pezcoller Foundation-FECS Recognition for Contribution to Oncology.

• 2004: Josephine Nefkens award, Erasmus University, Rotterdam.

• 1992: Pionier Award, Netherlands Organization for Scientific Research.

• 1989: Searle Scholarship award.

• 1988: Edward Mallinckrodt Foundation award.

• 1985: Constantijn and Christiaan Huygens Fellowship, Netherlands Organization for Scientific Research.

1. Prahallad, A., Sun, C., Huang, S., Di Nicolantonio, F., Salazar, R., Zecchin, D., ... & Bernards, R. (2012). Unresponsiveness of colon cancer to BRAF (V600E) inhibition through feedback activation of EGFR. Nature, 483(7388), 100.

2. Mainardi, S., Mulero-Sánchez, A., Prahallad, A., Germano, G., Bosma, A., Villanueva, A., Bardelli, A. and Bernards, R. (2018). PTPN11 inhibition impairs the growth of KRAS mutant Non-Small Cell Lung Cancer in vivo and sensitizes to MEK inhibition. Nature Med. 24, 961-967.

3. Wang, L., Leite de Oliveira, R., Huijberts, S., Bosdriesz, E., Pencheva, N., Brunen, D., Bosma, A., Song, J-Y., Zevenhoven, J., de Vries, T., Horlings, H., Nuijen, B., Beijnen, J.H., Schellens, J.H.M. and Bernards, R. (2018). An acquired vulnerability of drug resistant melanoma with therapeutic potential. Cell, 173, 1413-1425.

4. Wang, C., Vegna, S., Jin, H., Lieftink, C., Benedict, B., Cor Lieftink, C., Ramirez, C., Leite de Oliveira, R., Morris, B., Gadiot, J., du Chatinier, A., Wang, L., Gao, D., Evers, B., Jin, G., Xue, Z., Schepers, A., Jochems, F., Mulero Sanchez, A., Mainardi, S., te Riele, H., Beijersbergen, R.L., Qin, W., Akkari, L., and Bernards, R. (2019). Inducing and exploiting vulnerabilities for the treatment of liver cancer. Nature 574, 268–272.

5. Jin, H., Shi, Y., Lv, Y., Yuan, S., Ramirez, C.F.A., Lieftink, C., Wang, L., Wang, S., Wang, C., Henrique Dias, M., Jochems, F., Yang, Y., Bosma, A., Hijmans, E. M., de Groot, M.H.P., Cui, D., Zhou, Y., Ling, J., Wang, H., Guo, Y., Zheng, X., Isima, N., Wu, H., Sun, C., Beijersbergen, R.L., Akkari, L., Zhou, W., Zhai, B., Qin, W., and Bernards, R. (2021). EGFR activation limits response of liver cancer to lenvatinib. Nature 595, 730–734.

Reuven Agami started his research career as a PhD student working on the c-Abl kinase protein and apoptosis in the lab of Yosef Shaul at the Weizmann Institute of Science, Israel. In 1998 he moved to The Netherlands Cancer Institute, Amsterdam, as a postdoc fellow working on initiation and maintenance of DNA damage responses. In 2001 he began his own lab at the division of tumor biology at the Netherlands Cancer Institute working on stable inactivation of human genes by RNA interference as well as microRNAs. In 2008 he was chosen to become a division head of Gene regulation at the Netherlands Cancer Institute, Amsterdam. In 2009 he became professor at the department of Genetics, Erasmus medical center in Rotterdam. In 2014 he moved to head the division of Biological Stress Response at the Netherlands Cancer Institute, and since 2017 he is heading the division of Oncogenomics at the Netherlands Cancer Institute.

Major breakthroughs of Reuven Agami were the discovery of c-Abl/p73 interaction and its role in cell cycle arrest and apoptosis during his PhD, the role of cyclin D1 degradation following DNA damage during his Postdoc, as well as the development of pSUPER, the first RNAi vector for stable suppression of gene expression in mammalian cells, and the establishment of cancerous roles of numerous microRNAs and RNA binding proteins using novel genetic screening approaches as a young group leader. As a more senior investigator he contributed to understanding the role of alternative cleavage and polyadenylation of mRNAs (APA) in human disease, the functional role of regulatory DNA elements in cancer, the connection between transcription and translation, and finally the identification and utilization of amino acid shortages in cancer.

• 2016: Awarded ZonMW-TOP grant project on enhancers in breast and prostate cancer

• 2013: Awarded ERC advanced project on enhancer RNAs.

• 2011: VICI grant award, ZonMW website.

• 2010: ESCI Award Winner 2010, Basic/Translational Research ESCI website.

• 2009: Professor at the Genetics and Pathology departments of Erasmus Medical Center, Rotterdam

• 2008: Awarded ERC starting project on microRNA regulation

• 2008: Elected member of the central for biomedical genetics (CBG)

• 2008: Elected member of EMBO

• 2007: Awarded The Dr. Joseph Steiner Prize, Switzerland

• 2007 in Biel. 2006: Elected member of the young academy (DJA-KNAW).

• 2004: EMBO young investigator award.

• 2004: VIDI grant.

• 2004: European Young Investigator Award (EURYI).

• 2002: Elected fellow of the central for biomedical genetics (CBG).

• 2001: Netherlands Cancer Institute (AVL) award. 1999: EMBO long-term fellowship.

1. Brummelkamp, T. R., Bernards, R., & Agami, R. (2002). A system for stable expression of short interfering RNAs in mammalian cells. Science, 296(5567), 550-553.

2. Jenal, M., Elkon, R., Loayza-Puch, F., van Haaften, G., Kühn, U., Menzies, F. M., ... & Rubinsztein, D. C. (2012). The poly (A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites. Cell, 149(3), 538-553.

3. Kedde, M., Strasser, M. J., Boldajipour, B., Vrielink, J. A. O., Slanchev, K., le Sage, C., ... & Lund, A. H. (2007). RNA-binding protein Dnd1 inhibits microRNA access to target mRNA. Cell, 131(7), 1273-1286.

4. Korkmaz, G., Lopes, R., Ugalde, A. P., Nevedomskaya, E., Han, R., Myacheva, K., ... & Agami, R. (2016). Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9. Nature biotechnology, 34(2), 192.

5. Loayza-Puch, F., Rooijers, K., Buil, L. C., Zijlstra, J., Vrielink, J. F. O., Lopes, R., ... & van Tellingen, O. (2016). Tumour-specific proline vulnerability uncovered by differential ribosome codon reading. Nature, 530(7591), 490.

6. Slobodin, B., Han, R., Calderone, V., Vrielink, J. A. O., Loayza-Puch, F., Elkon, R., & Agami, R. (2017). Transcription impacts the efficiency of mRNA translation via co-transcriptional N6-adenosine methylation. Cell, 169(2), 326-337.

7. Voorhoeve, P. M., Le Sage, C., Schrier, M., Gillis, A. J., Stoop, H., Nagel, R., ... & Zlotorynski, E. (2006). A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell, 124(6), 1169-1181.

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