Peeper

Daniel Peeper

Group leader

d.peeper@nki.nl

Daniel Peeper is professor in Functional Oncogenomics VU University Amsterdam, heading the Department of Molecular Oncology & Immunology and chairing the Research Faculty Council Board at the Netherlands Cancer Institute (NKI). He set up and chaired the Translational Research Board at NKI (2014-2019).

He studied Medical Biology at the VU University Amsterdam and received his PhD in the laboratory of Alex van der Eb (Leiden, 1994) for his work on adenovirus oncoproteins and cell cycle proteins. He received his postdoctoral training in the lab of Mark Ewen (Dana-Farber Cancer Institute, Harvard Medical School, Boston) and subsequently the lab of René Bernards (NKI).

Previous highlights include his discoveries using functional genetics of a new metastasis gene (Nature 2004); that Oncogene-Induced cellular Senescence (OIS) serves as a tumor suppressor mechanism limiting cancer progression in humans (Nature 2005; New Engl J Med 2006); that OIS is associated with the activation of an inflammatory transcriptome (Cell 2008; Nat Rev Cancer 2009; Genes Dev 2010); that PTEN reduction acts as an OIS bypass mechanism driving melanoma development (Genes Dev 2012); and that pyruvate dehydrogenase kinase (PDK1) acts as a critical switch for the execution of OIS (Nature 2013).

His team uses function-based genetic screens to develop rational combinatorial cancer treatment, targeting both cancer and immune cells. They discovered a new mechanism mediating resistance to targeted therapy in melanoma involving the receptor tyrosine kinase AXL (Nature Comm. 2014) and established a large melanoma PDX platform with which they identified a novel resistance mechanism to BRAF inhibition (Cell Rep. 2016). Building on this finding, his laboratory developed a new rational concept for combinatorial targeting of intratumor heterogeneity, which is currently explored clinically (Nature Med. 2018). His group also dissected the mechanism of cancer drug addiction and provided PoC of how this vulnerability may be used clinically (Nature 2017).

Most recently, his laboratory has been developing rational cancer treatment, combining tumor and immune cell interventions. Focusing on the interface between tumor and immune cells, his team discovered that lowering the TNF threshold sensitizes tumors to T cell attack and immunotherapy (Cell 2019). As another example, they reported the existence of pre-existing NGFR-expressing melanoma cells that display resistance to several different treatments, including T cells (Nature Comm. 2020). Several potential new tumor and immune cell drug targets have been identified and are currently being studied in preclinical models. They also emphasized the urgent clinical need to develop rational combination treatments (Mol. Cell 2020).

The successful identification of new therapeutic IO targets led him to found, together with Maarten Ligtenberg and Christian Blank, an NKI spin-off company in immuno-oncology (Immagene).

Peeper has received several awards, including a KWF Queen Wilhelmina Award and a Society for Melanoma Research (SMR) Outstanding Researcher Award. He is an elected Member of Oncode, EMBO and Academia Europaea, and has been serving on the Board of the European Association for Cancer Research (EACR) since 2012.


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