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Oncogenomics: William Faller

William Faller

William Faller, Ph.D.Jr. Group Leader

About William Faller

Research interest

The Faller lab is studying the role that RNA translation plays in models of cancer. In recent years it has become clear that cancer cells use multiple mechanisms to up-regulate oncogenes and down-regulate tumour suppressor genes. Much of the focus of this research has been on modulators of transcription; however we now estimate that transcriptional control only explains 30% to 40% of protein level variation. One of the major reasons for this discrepancy is thought to be differences in RNA translation.

Colorectal cancer (CRC) is the second most common cause of cancer mortality, with around 700,000 deaths annually. While this number has been steadily decreasing over the last 4 decades, this has largely been as a result of screening programs, and our treatment options have lagged behind.

Our lab uses mouse models of CRC to study the effect that changes in RNA translation have on this disease. We have previously shown that CRC cells require increased RNA translation in order to proliferate. We also showed that by blocking this RNA translation we could protect mice from the disease. Our aim is now to fully understand the role that RNA translation plays, in order to identify therapeutic targets and potentially develop drugs that can target this process.

We have also pinpointed the elongation phase of RNA translation as being a crucial level of regulation in CRC. Interestingly, this regulation via elongation is specific for a subset of pro-proliferative RNAs. We want to understand why certain genes are regulated in this manner and others not. If we can understand this mechanism it may provide us with a rationale for targeting abnormal elongation in cancer with chemotherapy. Alternatively, by understanding which particular genes are regulated like this, it may be possible to target them instead. For example, we have shown that Cyclin D3 is controlled by elongation, while other highly homologous family members (Cyclin D1 and Cyclin D2) are not. Given its role as a regulator of the cell cycle, we are now trying to elucidate the importance of Cyclin D3 in the context of cancer.

Our lab aims to combine the use of innovative technologies with state-of-the-art mouse models, in order to give us a much more thorough understanding of the role that RNA translation plays in cancer, while at the same time identifying many new, exciting therapeutic targets for the disease.

Co-workers

rob

Rob van der Kammen

Technician

Experience

I am an experienced technician (>25 years) in cell biology, molecular biology and mouse models (In possession of art.12).   Started my career in Utrecht under supervision of Dr. Jansen and Dr de Pagter-Holthuizen where I worked on IGF1 and IGF-2.

In 1988 I joined the group of Dr. J Collard at the NKI , where I worked quite succesfully on Tiam1(mousemodels, skincancer). In 2009  I shifted gear and moved to the group of Metello Innocenti and worked on the formin Diaph3 and on  conditional mouse models regarding ARPC4 deletionto study the role of the Arp2/3 complex  in the skin. At present I relocated to the group of William Faller where I  work on intestinal cancer models (in vivo as well as in vitro).
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

  

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Da Silva, Faria

Joana Faria Da Silva

Postdoctoral Fellow

Experience

During my Master's degree in the Portuguese Institute of Oncology, I studied the impact that genetic polymorphisms have in both prognosis and diagnosis of different cancer types. I then moved to the IRB Barcelona where I did my doctorate under the supervision of Dr. Travis Stracker, characterizing the functions of a novel exonuclease that we found to be important for governing germ stem cells and lifespan by promoting mitoribosome integrity and translation. As a postdoc at the Faller lab, I am interested in understanding the mechanisms underlying translation regulation in intestinal stem cells and colon cancer.

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Alkan

Ferhat Alkan

Postdoctoral Fellow

Experience

After receiving my MSc degree in Computer Science from Istanbul Kadir Has University with a thesis focusing on comparative analysis of biological networks, I pursued my academic career with a PhD in University of Copenhagen, Denmark.  My PhD project was about designing fast computational approaches for the discovery of RNA interactions and apply these tools in biotechnology and disease research. This included developing off-targeting assessment tools for CRISPR-Cas9 and RNAi systems.In NKI, I will focus on large-scale integration of ribosome profiling, RNA structure prediction&probing and transcriptomic datasets to unravel the secrets of translational machinery in cancer cells.

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Ramalho, Ana Sofia

Sofia Ramalho

Ph.D. student

Experience

I completed my Bachelor's degree in Biochemistry and Master's degree in Oncobiology at the University of Lisbon (Portugal). During my Master's internship I studied interleukin-7 receptor-mediated signaling in acute lymphoblastic leukemia, under the supervision Professor João T. Barata at IMM (Portugal). I continued working in this project as a research fellow for one year after delivering my thesis. Motivated by my interest in oncobiology and wanting to explore new subjects, I have now joined the Faller Lab as a PhD student. I will be exploring the mechanisms involved in regulation of RNA translation in colon cancer and stem cells.

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Key publications View All Publications

  • mTORC1-mediated translational elongation limits intestinal tumour initiation and growth.

    Nature. 2015;22:517:497-500

    Faller WJ, Jackson TJ, Knight JR, Ridgway RA, Jamieson T, Karim SA, Jones C, Radulescu S, Huels DJ, Myant KB, Dudek KM, Casey HA, Scopelliti A, Cordero JB, Vidal M, Pende M, Ryazanov AG, Sonenberg N, Meyuhas O, Hall MN, Bushell M, Willis AE, Sansom OJ.

    Link to Pubmed
 
 

Recent publications View All Publications

  • A YY1-dependent increase in aerobic metabolism is indispensable for intestinal organogenesis.

    Development. 2016;143:3711-3722

    Kumar N, Srivillibhuthur M, Joshi S, Walton KD, Zhou A, Faller WJ, Perekatt AO, Sansom OJ, Gumucio DL, Xing J, Bonder EM, Gao N, White E, Verzi M.

    Link to Biologist
  • Fascin expression is increased in metastatic lesions but does not correlate with progression nor outcome in melanoma

    Melanoma Res. 2015;25:169-72

    Ma Y, Faller WJ, Sansom OJ, Brown ER, Doig TN, Melton DW, Machesky LM.

    Link to Pubmed
 

Contact

  • Office manager

    Elise Marseille

  • E-mail

    e.marseille@nki.nl

  • Telephone Number

    +31 (0)20 512 2015

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