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PhD W.J. Bakker

Position
Assistant Professor
Main activities
Research
Specialisation
Hypoxia / Gene expression / Cancer Biology / Tumor angiogenesis / Immunology
Focus of research

Tumor hypoxia is a hallmark of solid tumor development and an adverse prognostic factor as it promotes metastasis, as well as resistance to radio- and chemotherapy, and importantly also to immunotherapy. Tumor hypoxia, resulting from an instable and malfunctioning tumor vasculature, induces resistance to immunotherapy by promoting the formation of an immune suppressive tumor micro-environment. Recently we identified the hypoxia-induced HIF1-E2F7 transcription complex, involved in the regulation of tumor development and angiogenesis, and we are currently exploring if the hypoxia-induced immune suppressive tumor environment can by targeted through this novel complex.     

 

Key publications
  • Weijts B. G. M. W., Westendorp B., Hien B. T., Martínez-López L. M., Zijp M., Thurlings I., Thomas R. E., Schulte-Merker S., Bakker W. J., de Bruin A. Atypical E2Fs inhibit tumor angiogenesis Oncogene 2018;37 (2):271-276 [PubMed]
  • de Bruin Alain, Cornelissen Peter W. A., Kirchmaier Bettina C., Mokry Michal, Iich Elhadi, Nirmala Ella, Liang Kuo-Hsuan, D Végh Anna M., Scholman Koen T., Groot Koerkamp Marian J., Holstege Frank C., Cuppen Edwin, Schulte-Merker Stefan, Bakker Walbert J. Genome-wide analysis reveals NRP1 as a direct HIF1 alpha-E2F7 target in the regulation of motorneuron guidance in vivo Nucleic acids research 2016;44 (8):3549-3566 [PubMed]
  • Weijts Bart G. M. W., Bakker Walbert J., Cornelissen Peter W. A., Liang Kuo-Hsuan, Schaftenaar Frank H., Westendorp Bart, de Wolf Charlotte A. C. M. T., Paciejewska Maya, Scheele Colinda L. G. J., Kent Lindsey, Leone Gustavo, Schulte-Merker Stefan, de Bruin Alain E2F7 and E2F8 promote angiogenesis through transcriptional activation of VEGFA in cooperation with HIF1 EMBO journal 2012;31 (19):3871-3884 [PubMed]
  • Zaugg Kathrin, Yao Yi, Reilly Patrick T., Kannan Karuppiah, Kiarash Reza, Mason Jacqueline, Huang Ping, Sawyer Suzanne K., Fuerth Benjamin, Faubert Brandon, Kalliomäki Tuula, Elia Andrew, Luo Xunyi, Nadeem Vincent, Bungard David, Yalavarthi Sireesha, Growney Joseph D., Wakeham Andrew, Moolani Yasmin, Silvester Jennifer, ten Annick You, Bakker Walbert, Tsuchihara Katsuya, Berger Shelley L., Hill Richard P., Jones Russell G., Tsao Ming, Robinson Murray O., Thompson Craig B., Pan Guohua, Mak Tak W. Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress Genes & development 2011;25 (10):1041-1051 [PubMed]
  • Bakker Walbert J., Harris Isaac S., Mak Tak W. FOXO3a is activated in response to hypoxic stress and inhibits HIF1-induced apoptosis via regulation of CITED2 Molecular cell 2007;28 (6):941-953 [PubMed]
All Publications
Research programmes

Prof. PhD R.M. Luiten (Pigment cell disorders of the skin)

Luiten's research team is specialized in the immunopathogenesis and treatment of pigment cell disorders of the skin, including vitiligo and melanoma. Luiten's research has clearly established a positive relation between vitiligo and melanoma regression, by showing that 1) vitiligo patients have a three-fold decreased life-time risk of developing melanoma , 2) vitiligo is an autoimmunity against melanocytes in the skin, leading to loss of skin pigmentation, 3) melanoma patients who develop vitiligo, referred to as melanoma-associated leucoderma or vitiligo (MAL), have immunity reactive with both melanocytes and melanoma cells, 4) the appearance of MAL in melanoma patients is associated with favorable clinical outcome (progression free- and overall survival), and 5) vitiligo-inducing compound monobenzone combined with imiquimod and/or CpG induces anti-melanoma immunity and suppresses melanoma growth in mice and patients. This highlights vitiligo as a favorable sign for melanoma patients and the importance of its mechanism of action for melanoma treatment. The group has developed a new melanoma therapy consisting of monobenzone and immune stimulation (patent granted, preclinical and clinical proof-of-concept obtained). Their investigator-initiated clinical trial at the NKI-AVL shows local clinical responses of skin metastases and successful induction of anti-melanoma immunity in most patients. This therapy is developed further clinically. New projects include biomarker research for response of melanoma patients to immune checkpoint inhibitors, targeting of melanoma cell heterogeneity by vaccination immunotherapy and diagnosis and treatment of lentigo maligna. Vitiligo clinical research aims at improving skin suspension transplantation therapy and the development of  scoring systems for vitiligo disease activity. Biomarkers for the differential diagnosis of vitiligo and melanoma-associated vitiligo are studied, applicable in preventing immunesuppressive therapy in vitiligo patients with an undiagnosed melanoma. Luiten's group joined forces of the NFU expertise center on Pigment Disorders (AMC) with the skin tissue engineering expertise of prof Gibbs (VUMC), to apply this technology in vitiligo and melanoma immunotherapy research. 

 

Faculty
PhD W.J. Bakker
MD PhD M.W. Bekkenk
MD PhD M.A. Middelkamp Hup
MD PhD A. Wolkerstorfer

Postdocs
PhD W. Ouwerkerk

Others
BEng S. Chielie
BEng G. Krebbers
N.O.P. van Uden