Welcome to the website of the Peeper laboratory at the Netherlands Cancer Institute (NKI) Amsterdam. Our objective is to use advanced techniques including function-based oncogenomic approaches to dissect essential cancer cell signaling networks and identify novel pharmacologically tractable targets for therapeutic intervention.
Functional oncogenomics are a common tool of the lab. The development of cancer is a multistep process, involving distinct (epi)genetic changes. Each step is rate limiting for completion of the transformation process. The Peeper laboratory is interested in dissecting how these genetic defects cooperatively cause cancer. But we are taking this also a step further: we use function-based genetic approaches to screen for vulnerabilities of cancer cells in the context of targeted treatment, aiming to discover novel combinatorial intervention strategies.
New intervention strategies are a primary interest of the lab. To identify new cancer intervention strategies, we are studying how cells override oncogene-induced cellular senescence (OIS, a tumor-suppressing mechanism limiting the proliferative capacity of incipient cancer cells) and how senescence can be reactivated in tumors. We are also interested in identifying mechanisms driving (non-) oncogene addiction and metastasis, as well as finding means to enhance drug effectiveness and prevent drug resistance. To do this, we make use of advanced techniques, such as function-based genetic screens with 100,000-vector shRNA and other genetic libraries and next-generation sequencing, in combination with classical biochemical and genetic approaches. While we are studying a diverse array of tumor types, there is a focus on melanoma and breast cancer.
Highlights include our 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 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); and that OIS is associated with the activation of an inflammatory transcriptome (Cell 2008; Nat Rev Cancer 2009; Genes Dev 2010). We also discovered that PI3K activation represents a common rate-limiting event in melanoma progression (Genes Dev 2012). For breast cancer, we identified a prognostic genetic signature based on the transcription factor Fra-1, which we demonstrate is essential for driving metastasis (PNAS 2013). Most recently, we reported in Nature a key role for the mitochondrial gatekeeper enzyme pyruvate dehydrogenase (PDH) in OIS. We also identified one of its regulators, pyruvate dehydrogenase kinase 1 (PDK1), as a potential novel drug target in melanoma treatment (see paper). For more information about ongoing research, click here.
Daniel Peeper is head of the Division of Molecular Oncology at the NKI and a group leader. He is also a professor in Functional Oncogenomics at the VU University medical center (VUmc) Amsterdam. He received the 2007 Junior Researcher award from the Society for Melanoma Research, a Queen Wilhelmina Award (2 million €) from the Dutch Cancer Society in 2009 (see below), he was elected as EMBO YIP member in 2005 and as EMBO member three years later. He is also chair of the Scientific council at NKI. Recently, in a consortium with Anton Berns, Mike Stratton and others he received a 15M€ ERC Synergy award for the development of combinatorial cancer therapy.
This website will update you about the ongoing research in the Peeper lab, along with information about vacancies, our researchers, publications and contact and travel information.