Niet ge- definieerd

Department of Molecular Cell Biology

Aim

The Department of Molecular Cell Biology has a strong focus on Advanced Optical Microscopy and its application in Biomedical research. We create a platform for studying (sub)cellular processes in health and disease, with a focus on cardiovascular biology, oncology, and brain. A whole range of microscopic technologies, including widefield (spectroscopic) fluorescence, (resonant scanning) confocal, (resonant scanning) multiphoton, and (resonant scanning) super-resolution STED is present in the group and applied to cells and tissues. The created platform is open for use by researchers from research schools within Maastricht and for external users interested in exploring these techniques. Furthermore, the platform is taking part in the Euro-BioImaging node Advanced Multiomodal and Molecular Imaging (AMMMI) in Maastricht, of which Prof. van Zandvoort is the Node leader for microscopy-related techniques.

Key publications

  1. Ingrid Gomez, Ben Ward, Celine Souilhol, Chiara Recarti, Mark Ariaans, Jessica Johnston, Amanda Burnett, Marwa Mahmoud, Le Anh Luong, Laura West, Merete Long, Sion Parry, Rachel Woods, Carl Hulston, Birke Benedikter, Rohit Bazaz, Sheila Francis, Endre Kiss-Toth, Marc van Zandvoort, Andreas Schober, Paul Hellewell, Paul C. Evans and Victoria Ridger. Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium. Nature Communications (accepted). IF=13.4
  2. Anne Gemmink, Sabine Daemen, Helma J Kuijpers, Gert Schaart, Hans Duimel, Carmen López-Iglesias, Marc van Zandvoort, Kèvin Knoops, Matthijs K Hesselink. Super-resolution microscopy localizes Perilipin 5 at lipid droplet-mitochondria interaction sites and at lipid droplets juxtaposing to Perilipin 2. Accepted by BBA - Molecular and Cell Biology of Lipids IF=5.6
  3. Y. Yilin, L. Steinbusch, M. Nabben, D. Kapsokalyvas, M.A.M.J. van Zandvoort, P. Schönleitner, G. Antoons, P.J. Simons, W.A. Coumans, A. Geomini, D. Chanda, J.F.C. Glatz, D. Neumann, J.J.F.P. Luiken. Palmitate-induced vacuolar-type H+-ATPase inhibition feeds forward into insulin resistance and contractile dysfunction. Diabetes 2017, 66(6):1521-1534 IF=8.1
  4. Z. Wu, T. Rademakers, F. Kiessling, M. Vogt, E. Westein, C. Weber, R.T.A. Megens, and M.A.M.J. van Zandvoort. Multi-Photon Microscopy in Cardiovascular Research. Methods 2017, Non-invasive molecular imaging and theranostic probes 2017, April 18 IF=3.8
  5. C. Kuppe, C. van Roeyen, K. Berger, N. Kabgani, M. Vogt, M.A.M.J. van Zandvoort, B. Smeets, J. Floege, H. Gröne, and M. J. Moeller. Investigations of glucocorticoid action in GN. J Am Soc Nephr 2017, 28(5):1408-1420. IF=9.3
  6. P. Koczera, L. Appold, Y. Shi, A. Dasgupta, V. Pathak, T. Ojhe, S. Fokong, Z. Wu, M.A.M.J. van Zandvoort, O. Iranzo, A.J.C. Kuehne, A. Pich, F. Kiessling, T. Lammers. PBCA-based polymeric microbubbles for molecular imaging and drug delivery. J. Of Controled Release 2017, 259:128-135 IF=7.1
  7. A. Schueth, B. Spronck, W. Buurman, M.A. M. J. van Zandvoort, G. A. van Koeveringe. Age-related changes in murine bladder structure and sensory innervation: a multiphoton microscopy quantitative analysis. Age 2016 Feb;38(1):17 IF=4.1
  8. A. Gemmink, M. Bosma, H. Kuijpers, J. Hoeks, G. Schaart, M.A.M.J. van Zandvoort, P. Schrauwen, M. Hesselink. Decoration of intramyocellular lipid droplets with PLIN5 modulates fasting-induced insulin resistance and lipotoxicity in humans. Diabetologia. 2016 May;59(5): 1040-8 IF=6.7
  9. Sabine Daemen, Marc A.M.J. van Zandvoort, Matthijs K.C. Hesselink. Microscopy tools for the investigation of intracellular lipid storage and dynamics. Mol Metab. 2015 Dec 31;5(3):153-63 IF=5.5
  10. T. Lammers, P. Koczera, S. Fokong, F. Gremse, J. Ehling, M. Vogt, A. Pich, G. Storm, M. A.M.J. van Zandvoort, Fabian Kiessling. Theranostic USPIO-loaded microbubbles for mediating and monitoring blood-brain barrier permeation. Adv Funct Mater. 2015; 25(1):36-43. IF=10.4
  11. A. Baleanu-Curaj, Z. Wu, T. Lammers, C. Weber, M. van Zandvoort, F. Kiessling. Non-invasive molecular ultrasound monitoring of vessel healing following intravascular surgical procedures. Arterioscler Thromb Vasc Biol. 2015; 35(6): 1366-1373. IF=7.2
  12. M. Schmitt, R. Megens, A. Zernecke, K. Bidzhekov, N. van den Akker, T. Rademakers, M. van Zandvoort, T. Hackeng, R. Koenen, C. Weber. Endothelial JAM-A Guides Monocytes into Flow-Dependent Predilection Sites of Atherosclerosis. Circ. 2014, 129(1):66-76 IF=15.2
  13. U. Sadat, F. Jaffer, M. van Zandvoort, S. Nicholls, D. Ribatti, J. Gillard. Inflammation and neovascularization intertwined in atherosclerosis: Imaging of structural and molecular imaging targets. Circ. 2014, 130(9):786-94 IF=15.2
  14. X. Li, M. Zhu, M. Penfold, R. Koenen, A. Thiemann, K. Heyll, S. Akhtar, S. Koyadan, Z. Wu, F. Gremse, F. Kiessling, M. van Zandvoort, T. Schall, C. Weber, A. Schober. Activation of CXCR7 limits atherosclerosis and improves hyperlipidemia by increasing cholesterol uptake in adipose tissue.  Circ. 2014, 129(11):1244-53 IF=15.2
  15. T. Rademakers, K. Douma, T. Hackeng, E. Biessen, M. Post, S. Heeneman, M. van Zandvoort. Insights into plaque-associated neovascularization: assessment of structural and functional characteristics of plaque-associated microvasculature in mouse models of atherosclerosis. ATVB 2013:33(2): 249-56 IF=7.2
  16. Z. Wu, A. Baleanu-Curaj, T. Lammers, F. Kiessling, M. van Zandvoort. Rhodamine-loaded intercellular adhesion molecule-1-targeted microbubbles for dual-modality imaging under controlled shear stresses – A model study for atherosclerosis. Circulation Cardiovascular Imaging 2013 6:974-981 IF=6.6

Team leader
Prof. Marc van Zandvoort 
T: (+31) (0)43 3881361
E: mamj.vanzandvoort@maastrichtuniversity.nl

Research group
Researchers: Jos BroersTon HopmanDimitris Kapsokalyvas, Bert Schutte
Technicians:  Annick Haesevoets, Monique Ummelen
PhD students: Somaieh Ahmadian, Jobran Moshi, Stefan Mestrom, VacancyStudents: Merel Stiekema

School
CARIMGROWNUTRIMMHeNS

Niet ge- definieerd

Advanced optical microscopy of disease

Aim
The Molecular Imaging group aims at creating an advanced optical imaging platform for studying (sub)cellular processes in health and disease, with a focus on cardiovascular biology and pathology. A whole range of microscopic technologies, including widefield (spectroscopic) fluorescence, confocal, (resonant scanning) multiphoton, and super-resolution STED is developed and applied to cells and tissues. The created platform is available to researchers from research schools within Maastricht and for external users. Furthermore, the platform is taking part in the Euro-BioImaging node “Excellence in Imaging” Maastricht, of which Prof. van Zandvoort is the Node leader.

Team leader
Prof. Marc van Zandvoort
T: (+31) (0)43 3881361
mamj.vanzandvoort@maastrichtuniversity.nl

Research leader at Universitätsklinikum Aachen, Two-photon Core Facility
Staff members: Michael Vogt and PhD Vytautas Kucikas

Research group
Technicians: Annick Haesevoets, Mieke Henfling, Monique Ummelen
Researchers: Jos Broers, Ton Hopman, Dimitris Kapsokalyvas, PhD
PhD students: Somaieh Ahmadian, Jobran Moshi

School
CARIMGROWNUTRIMMHeNS

Publications

Niet ge- definieerd

Nuclear Lamins in Health and Disease

Aim
Nuclear lamins are key proteins in the mechanical functioning of cells. Especially, proteins from the LMNA gen (lamin A, lamin C and lamin Adel10) appear to determine cellular stiffness and mechanoresponse. Laminopathies arise in patients with LMNA mutations, with a disease phenotype ranging from Hutchison Gilford progeria to muscle and fat tissue–related disorders, such as dilated cardiomyopathy and partial lipodystrophy. In all, LMNA mutations lead to about 20 different clinical diseases, depending on the localisation of the mutation and as yet unknown additional factors in disease development.
In our group we study the cellular effects of LMNA mutations, using vital microscopy, advanced high-resolution microscopy (STED), Two-photon microscopy, as well as standard molecular techniques.

The impact of alterations in LMNA expression on mechanical properties of these cells is studied in close cooperation with Dr. Carlijn Bouten (Eindhoven University of Technology, Dept. of Biomedical engineering).

Detailed microscopic analyses of dermal fibroblast from patients with LMNA mutations will lead to functional assays to predict disease development. These studies are performed in close cooperation with dr. Arthur van den Wijngaard (Maastricht University, Dept. of Clinical genetics, Cardiogenetics).

The downregulation of A-type lamins leads to increased mobility of tumor cells, allowing improved capabilities of tumor invasion and metastasis. Together with Dr. Jürgen Becker (Translational Skin Cancer Research, German Cancer Consortium (DKTK), University Hospital Essen, Germany) we investigate the impact of LMNA downregulation on the behavior of Merkel cell carcinomas.

Key publications

  1. Assessment of fibroblast nuclear morphology aids interpretation of LMNA variants. van Tienen FHJ, Lindsey PJ, Kamps MAF, Krapels IP, Ramaekers FCS, Brunner HG, van den Wijngaard A, Broers JLV. Eur J Hum Genet. 2019 Mar;27(3):389-399.
    Select item 287901525.
  2. Lamin A/C-Related Cardiac Disease: Late Onset With a Variable and Mild Phenotype in a Large Cohort of Patients With the Lamin A/C p.(Arg331Gln) Founder Mutation. Hoorntje ET, Bollen IA, Barge-Schaapveld DQ, van Tienen FH, Te Meerman GJ, Jansweijer JA, van Essen AJ, Volders PG, Constantinescu AA, van den Akker PC, van Spaendonck-Zwarts KY, Oldenburg RA, Marcelis CL, van der Smagt JJ, Hennekam EA, Vink A, Bootsma M, Aten E, Wilde AA, van den Wijngaard A, Broers JL, Jongbloed JD, van der Velden J, van den Berg MP, van Tintelen JP. Circ Cardiovasc Genet. 2017 Aug;10(4).
  3. Lmna knockout mouse embryonic fibroblasts are less contractile than their wild-type counterparts. van Loosdregt IAEW, Kamps MAF, Oomens CWJ, Loerakker S, Broers JLV, Bouten CVC. Integr Biol (Camb). 2017 Aug 14;9(8):709-721.
  4. Cellular strain avoidance is mediated by a functional actin cap - observations in an Lmna-deficient cell model. Tamiello C, Halder M, Kamps MA, Baaijens FP, Broers JL, Bouten CV. J Cell Sci. 2017 Feb 15;130(4):779-790.
  5. Tamiello C, Buskermolen AB, Baaijens FP, Broers JLV, Bouten CV. Heading in the right direction: understanding cellular orientation responses to complex biophysical environments. Cell Mol Bioeng 9:12-37, 2016.
  6. Broers JL, Ramaekers FC. The role of the nuclear lamina in cancer and apoptosis. Adv Exp Med Biol 773:27-48, 2014.
  7. Tamiello C, Kamps MA, van den Wijngaard A, Verstraeten VL, Baaijens FP, Broers JL, Bouten CC. Soft substrates normalize nuclear morphology and prevent nuclear rupture in fibroblasts from a laminopathy patient with compound heterozygous LMNA mutations. Nucleus 4:61-73, 2013.
  8. De Vos WH, Houben F, Kamps M, Malhas A, Verheyen F, Cox J, Manders EM, Verstraeten VL, van Steensel MA, Marcelis CL, van den Wijngaard A, Vaux DJ, Ramaekers FC, Broers JL. Repetitive disruptions of the nuclear envelope invoke temporary loss of cellular compartmentalization in laminopathies. Hum Mol Genet 20:4175-4186, 2011.
  9. Verstraeten VL, Broers JL, van Steensel MA, Zinn-Justin S, Ramaekers FC, Steijlen PM, Kamps M, Kuijpers HJ, Merckx D, Smeets HJ, Hennekam RC, Marcelis CL, van den Wijngaard A. Compound heterozygosity for mutations in LMNA causes a progeria syndrome without prelamin A accumulation. Hum Mol Genet. 15:2509-2522, 2006.
  10. Broers JL, Ramaekers FC, Bonne G, Yaou RB, Hutchison CJ. Nuclear lamins: laminopathies and their role in premature ageing. Physiol Rev 86:967-1008, 2006.
  11. Broers JL, Peeters EA, Kuijpers HJ, Endert J, Bouten CV, Oomens CW, Baaijens FP, Ramaekers FC. Decreased mechanical stiffness in LMNA-/- cells is caused by defective nucleo-cytoskeletal integrity: implications for the development of laminopathies. Hum Mol Genet 13:2567-2580, 2004.
  12. Broers JL, Machiels BM, van Eys GJ, Kuijpers HJ, Manders EM, van Driel R, Ramaekers FC. Dynamics of the nuclear lamina as monitored by GFP-tagged A-type lamins. J Cell Sci. 112:3463-3475, 1999.

Team leader
Jos Broers, PhD
T: (+31) (0)43 3881366
E: jos.broers@maastrichtuniversity.nl

Research group
Research: Prof. M. van Zandvoort
Technicians: Monique Ummelen, Annick Haesevoets
PhD students: Merel Stiekema

School
CARIM, GROW

Niet ge- definieerd

Molecular and cell biology of cervical (pre)malignancies

Aim
The research focusses on unravelling of the molecular processes during the development of the (pre)malignant stages of cervical cancer. These processes include the initial steps during cervical carcinogenesis, in particular the study of the progenitor cell that is targeted by the Human Papilloma Virus (HPV). Furthermore, questions with respect to the different types of stem cell populations in the ecto- and endo cervix are being addressed by means of specific immunomarkers. In doing so, the molecular processes involved in the development of premalignant lesions into an invasive carcinoma can be monitored.

Since we have shown that integration of the virus into the host genome can affect the progression of cervical premalignancies, advanced molecular protocols are being developed to detect HPV subtypes and their physical status. These techniques include the Multiplex Ligation-dependent Probe Amplification (MLPA) and Single tube Multiplex Amplification in Real Time (SMART). To detect the genomic instability during progression of the lesions, fluorescent in situ hybridization protocols have been developed and optimized. These assays allow the detection of chromosomal aberrations and can distinguish between the episomal and integrated physical status of the virus. Improved immunocytochemical techniques have been developed for the sensitive and reproducible detection of proliferation and differentiation markers, such as different keratins and SOX transcription factors. Finally, more recent studies have focused on methylation of specific genes involved in the cervical carcinogenesis.

Key publications

  1. SOX17 expression and its down-regulation by promoter methylation in cervical adenocarcinoma in situ and adenocarcinoma. Hopman ANH, Moshi JM, Hoogduin KJ, Ummelen M, Henfling MER, van Engeland M, Wouters KAD, Stoop H, Looijenga LHJ, Ramaekers FCS. Histopathology. 2019 Aug 23.
  2. Gain of Chromosomal Region 3q26 as a Prognostic Biomarker for High-Grade Cervical Intraepithelial Neoplasia: Literature Overview and Pilot Study. Koeneman MM, Ovestad IT, Janssen EAM, Ummelen M, Kruitwagen RFPM, Hopman AH, Kruse AJ. Pathol Oncol Res. 2019 Apr;25(2):549-557
  3. Molecular characterization, prevalence and clinical relevance of Phodopus sungorus papillomavirus type 1 (PsuPV1) naturally infecting Siberian hamsters (Phodopus sungorus). Kocjan BJ, Hošnjak L, Račnik J, Zadravec M, Bakovnik N, Cigler B, Ummelen M, Hopman AHN, Gale N, Švara T, Gombač M, Poljak M. J Gen Virol. 2017 Nov;98(11):2799-2809.
  4. Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial. Koeneman MM, Kruse AJ, Kooreman LF, Zur Hausen A, Hopman AH, Sep SJ, Van Gorp T, Slangen BF, van Beekhuizen HJ, van de Sande AJ, Gerestein CG, Nijman HW, Kruitwagen RF. BMC Cancer. 2017 Feb 7;17(1):110.
  5. Hopman A.H.N., Ramaekers F.C.S.: Development of the uterine cervix; and its implications for the pathogenesis of cervical cancer. In: Essentials of diagnostic gynecological pathology. Pathology of the cervix (S. Herrington) Springer 2017, in press.
  6. Koeneman MM, Kruse AJ, Kooreman LF, Zur Hausen A, Hopman AH, Sep SJ, Van Gorp T, Slangen BF, van Beekhuizen HJ, van de Sande M, Gerestein CG, Nijman HW, Kruitwagen RF. OPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC trial): study protocol for a randomized controlled trial. BMC Cancer. 2016, 20;16:132.
  7. Ossel J, Litjens RJ, Reijans M, Brink AA, Ummelen M, Ramaekers FC, Hopman AH, Simons G. Human papillomavirus typing by single tube multiplex amplification in real time (SMART): the PapillomaFinder® SMART 20 assay. J Clin Virol. 2014, 61:540-7
  8. Bergshoeff VE, Van der Heijden SJ, Haesevoets A, Litjens SG, Bot FJ, Voogd AC, Chenault MN,Hopman AH, Schuuring E, Van der Wal JM, Manni JJ, Ramaekers FC, Kremer B, Speel EJ. Chromosome instability predicts progression of premalignant lesions of the larynx.Pathology. 2014, 46:216-24
  9. Litjens RJ, Van de Vijver KK, Hopman AH, Ummelen MI, Speel EJ, Sastrowijoto SH, Van Gorp T, Slangen BF, Kruitwagen RF, Krüse AJ. The majority of metachronous CIN1 and CIN3 lesions are caused by different human papillomavirus genotypes, indicating that the presence of CIN1 seems not to determine the risk for subsequent detection of CIN3.Hum Pathol. 2014, 45:221-6
  10. Theelen W, Litjens RJ, Vinokurova S, Haesevoets A, Reijans M, Simons G, Smedts F, Herrington CS, Ramaekers FC, von Knebel Doeberitz M, Speel EJ, Hopman AHHuman papillomavirus multiplex ligation-dependent probe amplification assay for the assessment of viral load, integration, and gain of telomerase-related genes in cervical malignancies.Hum Pathol. 2013, 44:2410-8
  11. Litjens RJ, Theelen W, van de Pas Y, Ossel J, Reijans M, Simons G, Speel EJ, Slangen BF, Ramaekers FC, Kruitwagen RF, Hopman AHUse of the HPV MLPA assay in cervical cytology for the prediction of high grade lesions. J Med Virol. 2013, 85:1386-93
  12. Litjens RJ, Hopman AH, van de Vijver KK, Ramaekers FC, Kruitwagen RF, Kruse AJ. Molecular biomarkers in cervical cancer diagnosis: a critical appraisal.Expert Opin Med Diagn. 2013, 7:365-77
  13. Mooren JJ, Kremer B, Claessen SM, Voogd AC, Bot FJ, Peter Klussmann J, Huebbers CU, Hopman AH, Ramaekers FC, Speel EJ. Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis.Int J Cancer. 2013, 15;1781-9
  14. Theelen W, Speel EJ, Herfs M, Reijans M, Simons G, Meulemans EV, Baldewijns MM, Ramaekers FC, Somja J, Delvenne P, Hopman AHIncrease in viral load, viral integration, and gain of telomerase genes during uterine cervical carcinogenesis can be simultaneously assessed by the HPV 16/18 MLPA-assay. Am J Pathol. 2010, 177:2022-33
  15. Smedts F, Ramaekers FC, Hopman AHThe two faces of cervical adenocarcinoma in situ. Int J Gynecol Pathol. 2010, 29:378-85
    ​​

Team leader
Ton Hopman, PhD
T: (+31) (0)43 3881358
E: hopman@maastrichtuniversity.nl

Research group
Research technicians: Monique Ummelen
PhD students: Jobran Moshi, Stefan Mestrom

School
GROW

  • Department of Molecular Cell Biology

    Aim

    Dit is er niet
  • Advanced optical microscopy of disease

    Dit is er niet
  • Nuclear Lamins in Health and Disease

    Dit is er niet
  • Molecular and cell biology of cervical (pre)malignancies

    Dit is er niet