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Jacqueline Cloos, Ph.D., is Research coordinator of the Department of Pediatric Oncology/Hematology and Senior investigator in the Department of Hematology
at the VU University medical center.
Research Focus
Our research is focused on hematologic malignancies with emphasis on leukemia in both adults and children. In addition, for childhood oncology we also
investigate brain tumors and retinoblastoma. We mainly have in vitro model systems consisting of established cell lines and primary patient samples. Our
laboratory research aims to find new tumor specific markers to enhance current chemo- and radiotherapy with less side-effects. In addition, we aim to find
new treatment targets in relevant signal transduction pathways for innovative therapy such as for example tyrosine kinase inhibitors. Currently we are encaging
more on eradication of the stem cells at minimal residual disease level and we put effort in identifying and isolating these cells that are supposed to be responsible
for the development of relapse and thereby treatment failure. Moreover, we also have interest in immunotherapy and perform research on immune escape mechanisms of
acute myeloid leukemia cells in order to increase recognition of the tumor cells by the immune system.
Areas of expertise
Cell biology:
Flow cytometry (multi-colour and sorting),Minimal residual disease measurements (leukemia associated phenotypes), stem cells identification (CD34+,CD38- and side population) in leukemia and solid tumors
Cell culture:
Normal lymphoblastoid, Leukemia, Medulloblastoma and Retinoblastoma cell lines and primary patient samples are cultured. For functional investigations we perform gene transfection (Amaxa nucleofector) and transduction. Phosphorylation status of relevant keyplayers in signal transduction such as AKT and NFkB is determined using FACS.
We have cultured cells with stromal components in trans-well systems and with untreated or cytarabine-treated human fibroblastic stromal HS-5 or primary human bone marrow stromal cells.
Molecular biology:
(real-time) PCR with Lightcycler and Taqman, sequencing and genescan analysis (ABI 3300), methylation specific PCR and MLPA technique, cloning and all standard molecular biolological techniques.
Cytotoxicity Testing:
MTT assay, growth curves, clonogenic assays and apoptosis measurements using FACS. For determining direct DNA induction we have optimized a specific sandwich ELISA with antibodies directed against single stranded DNA. Chromosomal instability is determined using the mutagen sensitivity assay in cultured lymphocytes exposed to the DNA damaging agent bleomycin.
Miscellaneous:
Western blotting, NFkB activity measurements, immunihisto- and cytochemistry, phage display
Personnel
Publications, specific research topics and lists of persons working in both departments can be found in the following two websites: www.hematologie.nl and www.vumc.nl/hoi/onderzoek.
Relevant Publications
Dirksen EH, Pinkse MW, Rijkers DT, Cloos J, Liskamp RM, Slijper M, Heck AJ. Investigating the dynamic nature of the interactions between nuclear proteins and histones upon DNA damage using an immobilized peptide chemical proteomics approach. J Proteome Res. 2006;5(9):2380-8.
Vink J, Cloos J, Kaspers GJ. Proteasome inhibition as novel treatment strategy in leukaemia. Br J Haematol. 2006;134(3):253-62.
Braakhuis BJ, Senft A, de Bree R, de Vries J, Ylstra B, Cloos J, Kuik DJ, Leemans CR, Brakenhoff RH. Expression profiling and prediction of distant metastases in head and neck squamous cell carcinoma. J Clin Pathol. 2006;5 Ahead of print.
Cloos J, Goemans BF, Hess CJ, van Oostveen JW, Waisfisz Q, Corthals S, de Lange D, Boeckx N, Hahlen K, Reinhardt D, Creutzig U, Schuurhuis GJ, Zwaan ChM, Kaspers GJ. Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples. Leukemia. 2006;20(7):1217-20.
Cloos J, de Boer WP, Snel MH, van den Ijssel P, Ylstra B, Leemans CR, Brakenhoff RH, Braakhuis BJ. Microarray analysis of bleomycin-exposed lymphoblastoid cells for identifying
cancer susceptibility genes. Mol Cancer Res. 2006;4(2):71-7.
Dirksen EH, Cloos J, Braakhuis BJ, Brakenhoff RH, Heck AJ, Slijper M. Human lymphoblastoid proteome analysis reveals a role for the inhibitor of acetyltransferases complex in DNA double-strand break response. Cancer Res. 2006;66(3):1473-80.
Oerlemans R, van der Heijden J, Vink J, Dijkmans BA, Kaspers GJ, Lems WF, Scheffer GL, Ifergan I, Scheper RJ, Cloos J, Assaraf YG, Jansen G. Acquired resistance to chloroquine in human CEM T cells is mediated by multidrug resistance-associated protein 1 and provokes high levels of cross-resistance to glucocorticoids. Arthritis Rheum. 2006;54(2):557-68.
Hubeek I, Stam RW, Peters GJ, Broekhuizen R, Meijerink JP, van Wering ER, Gibson BE, Creutzig U, Zwaan CM, Cloos J, Kuik DJ, Pieters R, Kaspers GJ. The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia. Br J Cancer. 2005;93(12):1388-94.
Hubeek I, Litvinova E, Peters GJ, Broekhuizen R, Haarman EG, Huismans DR, Cloos J, Zwaan CM, Fleischhack G, Creutzig U, Kaspers GJ. The effect of G-CSF on the in vitro cytotoxicity of cytarabine and fludarabine in the FLAG combination in pediatric acute myeloid leukemia. Int J Oncol. 2004;25(6):1823-9.
Adema AD, Cloos J, Verheijen RH, Braakhuis BJ, Bryant PE. Comparison of bleomycin and radiation in the G2 assay of chromatid breaks. Int J Radiat Biol. 2003;79(8):655-61.
Woelfle U, Cloos J, Sauter G, Riethdorf L, Janicke F, van Diest P, Brakenhoff R, Pantel K. Molecular signature associated with bone marrow micrometastasis in human breast cancer. Cancer Res. 2003;63(18):5679-84.
Cloos J, Temmink O, Ceelen M, Snel MH, Leemans CR, Braakhuis BJ. Involvement of cell cycle control in bleomycin-induced mutagen sensitivity. Environ Mol Mutagen. 2002;40(2):79-84.
Colnot DR, Wilhelm AJ, Cloos J, Roos JC, de Bree R, Quak JJ, Snow GB, van Dongen GA. Evaluation of limited blood sampling in a preceding 99mTc-labeled diagnostic study to predict the pharmacokinetics and myelotoxicity of 186Re-cMAb U36 radioimmunotherapy. J Nucl Med. 2001;42(9):1364-7.
Aben KK, Cloos J, Koper NP, Braakhuis BJ, Witjes JA, Kiemeney LA. Mutagen sensitivity in patients with familial and non-familial urothelial cell carcinoma. Int J Cancer 2000;88(3):493-6.
Cloos J, Leemans CR, van der Sterre ML, Kuik DJ, Snow GB, Braakhuis BJ. Mutagen sensitivity as a biomarker for second primary tumors after head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2000;9(7):713-7.
Cloos J, Reid CB, van der Sterre ML, Tobi H, Leemans CR, Snow GB, Braakhuis
BJ. A comparison of bleomycin-induced damage in lymphocytes and primary oral
fibroblasts and keratinocytes in 30 subjects. Mutagenesis. 1999;14(1):87-93.
Cloos J, Willems EM, van Warmerdam JM, Braakhuis BJ, Snow GB, Meijer S. Mutagen sensitivity in common cutaneous malignant melanoma and dysplastic naevus syndrome.
Melanoma Res. 1999;9(3):292-6.
Cloos J, Nieuwenhuis EJ, Boomsma DI, Kuik DJ, van der Sterre ML, Arwert F, Snow GB, Braakhuis BJ. Inherited susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes. J Natl Cancer Inst. 1999;91(13):1125-30.
Copper MP, Klaassen I, Brakenhoff RH, Cloos J, Snow GB, Braakhuis BJ. All-trans retinoic acid induced gene expression and growth inhibition in head and neck cancer cell lines. Oral Oncol. 1997;33(4):270-4.
Welters MJ, Fichtinger-Schepman AM, Baan RA, Hermsen MA, van der Vijgh WJ, Cloos J, Braakhuis BJ. Relationship between the parameters cellular differentiation, doubling time and platinum accumulation and cisplatin sensitivity in a panel of head and neck cancer cell lines. Int J Cancer. 1997;71(3):410-5.
Braakhuis BJ, Klaassen I, van der Leede BM, Cloos J, Brakenhoff RH, Copper MP, Teerlink T, Hendriks HF, van der Saag PT, Snow GB. Retinoid metabolism and all-trans retinoic acid-induced growth inhibition in head and neck squamous cell carcinoma cell lines.
Br J Cancer. 1997;76(2):189-97.
Cloos J, Bongers V, Lubsen H, Tobi H, Braakhuis BJ, Snow GB. Lack of effect of daily N-acetylcysteine supplementation on mutagen sensitivity. Cancer Epidemiol Biomarkers Prev. 1996;5(11):941-4.
Cloos J, Spitz MR, Schantz SP, Hsu TC, Zhang ZF, Tobi H, Braakhuis BJ, Snow GB.
Genetic susceptibility to head and neck squamous cell carcinoma. J Natl Cancer Inst. 1996;88(8):530-5.
Cloos J, Gille JJ, Steen I, Lafleur MV, Retel J, Snow GB, Braakhuis BJ. Influence of the antioxidant N-acetylcysteine and its metabolites on damage induced by bleomycin in PM2 bacteriophage DNA. Carcinogenesis. 1996;17(2):327-31.
Cloos J, Braakhuis BJ, Steen I, Copper MP, de Vries N, Nauta JJ, Snow GB. Increased mutagen sensitivity in head-and-neck squamous-cell carcinoma patients, particularly those with multiple primary tumors. Int J Cancer. 1994;56(6):816-9.
Contact Details
Jacqueline Cloos, Ph.D.
Department of Pediatric Oncology/Hematology
VU university medical center
Cancer Center Amsterdam (room 3.26)
De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
Phone: +31 20 4447413
E-mail
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