Research interest
Resolving cancer cell networks & identifying cancer drug targets
What are the cellular mechanisms protecting us against cancer? How can we effectively identify novel cancer genes? How can we resolve tumor-suppressing genetic networks? Can we use our laboratory results to make a difference in the clinic? For example, how can we identify novel drug targets?
In a nutshell, these are the fundamental as well as clinically relevant questions that we are taking up in the Peeper laboratory. In doing so, we aim to get more insight into the central mechanisms disrupting cellular protection against oncogenic processes. And by exploiting unbiased genomic approaches, we intend to identify novel and selective cancer drug targets.
To reach these goals, we are combining function-based, genome-wide screens with classical molecular biological approaches. For example, we are studying the genetic basis for malignant progression of benign moles (nevi) to malignant melanoma. We, in collaboration with Wolter Mooi (VUmc), were the first to discover that nevi display all the classical hallmarks of Oncogene-Induced Senescence (OIS). We have also designed several functional genomic screens with retroviral and lentiviral cDNA expression and RNA interference libraries. For example, using OIS as a cancer-relevant cell-based experimental setting, we have identified novel oncogenes and tumor suppressor genes. Along these lines, we have recently discovered an unanticipated role for interleukins and the inflammatory transcriptome in cellular senescence (named Senescence-Messaging Secretome, or SMS). This process may contribute to preventing colon cancer progression.
Furthermore, we have designed a new in-vitro screen for metastasis genes, based on suppression of anoikis (detachment-induced cell death). This screen identified a tyrosine kinase receptor (TrkB) that is overexpressed in metastasizing human tumors. Further taking advantage of this experimental system, we have recently discovered a novel and critical mediator of breast cancer metastasis, which also accurately predicts clinical outcome.
The Peeper laboratory also intends to translate information from its in-vitro experiments to the clinic. For example, in collaboration with pharma industry we are currently validating TrkB as a novel drug target. Furthermore, we have begun setting up so-called synthetic lethality screens as a direct and efficient approach to discover novel cancer drug targets.
We anticipate that these lines of research, together, will not only unravel genetic networks that upon deregulation contribute to cancer and metastasis. In addition, the genes that we are identifying may represent novel and specific targets for therapeutic intervention of cancer.
Key publications
Kuilman T. and Peeper, D.S. (2009). Senescence-Messaging Secretome: SMS-ing cellular stress. Nature Reviews Cancer, Jan 9. [Epub ahead of print]
Kuilman, T., Michaloglou, C., Vredeveld, L.C.W., Douma, S., van Doorn, R., Desmet, C.J., Aarden, L.A., Mooi, W.J., and Peeper, D.S. (2008). Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133, 1019-31.
Smit M.A. and Peeper D.S. (2008). Deregulating EMT and senescence: double impact by a single Twist. Cancer Cell. 14, 5-7.
Prieur A. and Peeper D.S. (2008). Cellular senescence in vivo: a barrier to tumorigenesis. Curr Opin Cell Biol. 20, 150-155.
Michaloglou, C, Vredeveld, L.C.W., Mooi, W.J. and Peeper, D.S. (2008). BRAFE600 in benign and malignant human tumours. Oncogene 27, 877-95.
Mooi, W.J. & Peeper, D.S. (2006). Oncogene-induced cell senescence - halting on the road to cancer. N Engl J Med. 355, 1037-46.
Rowland, B.D. and Peeper, D.S. (2006). KLF4, p21 and context-dependent opposing forces in cancer. Nature Reviews Cancer 6, 11-23.
Rowland, B.D., Bernards, R. and Peeper, D.S. (2005). The KLF4 tumor suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene. Nature Cell Biol. 7, 1074-1082.
Michaloglou, C, Vredeveld, L.C.W., Soengas, M.S., Denoyelle, C., Kuilman, T., Van der Horst, C.M.A.M., Majoor, D.M., Shay, J.W., Mooi, W.J. and Peeper, D.S. (2005). BRAFE600-associated senescence-like cell cycle arrest of human nevi. Nature 436, 720-724
Douma, S., van Laar, T., Zevenhoven, J., Meuwissen, R., van Garderen, E. and Peeper, D.S. (2004). Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature 430, 1034-1039.
Rowland, B.D., Bernards, R. and Peeper, D.S. (2002). E2F repressor complexes are critical for p19Arf/p53-induced replicative arrest. Cancer Cell 2, 55-65.
Peeper, D.S., Shvarts, A., Brummelkamp, T., Douma, S., Koh, E.Y., Daley, G.Q. and Bernards, R. (2002). A functional screen identifies hDRIL1 as an oncogene that rescues RAS-induced senescence. Nature Cell Biol. 4, 148-153.
Peeper, D.S., Dannenberg, J.H., Douma, S., te Riele, H., and Bernards, R. (2001). Escape from premature senescence is not sufficient for oncogenic transformation by RAS. Nature Cell Biol. 3, 198-203.
Peeper, D.S., Upton, T.M., Ladha, M.H., Neuman, E., Zalvide, J., Bernards, R., DeCaprio, J.A., and Ewen, M.E. (1997). Ras signalling linked to the cell-cycle machinery by the retinoblastoma protein. Nature 386, 177-181.
More publications by Daniel Peeper on PubMed
Biographic sketch
Daniel Peeper received his PhD in the laboratory of professor Alex van der Eb at the University of Leiden (The Netherlands, 1994), for his work on adenoviral oncoproteins and cell cycle-regulatory proteins. He received his first postdoctoral training in the laboratory of Mark Ewen (Dana-Farber Cancer Institute, Boston, USA), where he discovered a functional connection between the Ras signaling protein and the retinoblastoma tumor suppressor protein. During a second postdoctoral period in the laboratory of professor René Bernards (Netherlands Cancer Institute), he studied cellular protection against oncogenic transformation, using function-based genome-wide screens.
He received a senior research position at the Netherlands Cancer Institute in 2000. Since 2002 as a principal investigator and since 2005 as Associated Professor he has been running his own laboratory at this institute, in the Division of Molecular Genetics. In 2008, he received a Professor appointment (part time) in Functional Oncogenomics at the VU university medical center (VUmc) in Amsterdam.
Peeper’s laboratory at NKI is dedicated to resolve cancer cell networks, aiming to identify novel anticancer drug targets. With classical biochemical and genetic approaches, as well as with newly designed function-based cellular screens, his group focuses on two cancer-relevant events: bypass of oncogene-induced senescence (‘OIS’, which limits the proliferative capacity of cells) and suppression of ‘anoikis’ (apoptosis resulting from lack of adhesion, suppression of which may contribute to metastasis). Furthermore, in collaboration with Wolter Mooi (VUmc) his group was the first to discover that human melanocytic nevi (skin ‘moles’; common, benign tumors of cutaneous melanocytes) display all the classical hallmarks of OIS. Recently, his group discovered an unanticipated role for interleukins and the inflammatory transcriptome in cellular senescence. Finally, his group recently discovered a novel and critical mediator of breast cancer metastasis, which can also predict clinical outcome.
In 2005, Peeper was elected as an EMBO Young Investigator. In 2006, he was awarded an NWO VICI grant (€ 1,2 million) on synthetic lethality screens for novel anticancer drug targets. In 2007, he (in collaboration with Wolter Mooi) was among the four researchers in the Netherlands to receive the first Netherlands Cancer Society (KWF) Queen Wilhelmina Programme Grant (€ 2 million), for a translational research project on melanoma. In the same year, he received the Society for Melanoma Research (SMR) Jr. Researcher Award 2007. In 2008, he was elected as EMBO member.
Co-workers
Anirudhan, Gireesh PhD Postdoctoral fellow
Gallenne, Tristan PhD Postdoctoral fellow
Geiger, Thomas MSc Postdoctoral fellow
Hoemig, Cornelia PhD Postdoctoral fellow
Lenain, Christelle MD PhD Postdoctoral fellow
Meissl, Katrin PhD Postdoctoral fellow
Vogel, Celia Postdoctoral fellow
Kaplon, Joanna MSc Graduate student
Kuilman,Thomas MSc Graduate student
Michaloglou, Chrysiis BSc Graduate student
Vredeveld, Liesbeth MSc Graduate student
Smit, Marjon MSc Graduate student
Rosado, Aranzazu BSc Technical staff
Douma, Sirith MSc Technical staff
Positions available
Please check home page Daniel Peeper.