Relevant Publications

Reviews Papers:

Langenkamp E, Kamps JA, Mrug M, Verpoorte E, Niyaz Y, Horvatovich P, Bischoff R, Struijker-Boudier H, Molema G (2013). Innovations in studying in vivo cell behaviour and pharmacology in complex tissues - microvascular endothelial cells in the spotlight. Cell Tissue Res, 354(3):647-69.

The review describes how the complexity of in vivo tissues urges us to study cell biology and drug effects in these environments and how the combination of laser microdissection and novel advancements in read out technologies such as proteomics, kinomics and transcriptomics will contribute to a more effective drug development process.

Oncology:

Skalicky S, Zwiers PJ, Kuiper T,  Schraml E, Hackl M, and Molema G (2019), Combining Laser Microdissection and microRNA Expression Profiling to Unmask microRNA Signatures in Complex Tissues. Biotechniques, 67(6): 276-285

Combination of Laser microdissection with microRNA profiling shows that in tumor tissue the tumor cells, stromal cells, and tumor microvasculature have a compartment specific miR signature that can be used for e.g., further biomarker evaluation and validation.

Dieterich LC, Mellberg S, Langenkamp E, Zhang L, Zieba A, Salomaki H, Teichert M, Huang H, Edqvist PH, Kraus T, Augustin HG, Olofsson T, Larsson E, Soderberg O, Molema G, Ponten F, Georgii-Hemming P, Alafuzoff I, and Dimberg A (2012), Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGF-beta2 in vascular abnormalization. J Pathol, 228 (3): 378-390.

Laser microdissection of FITC-UEA-1 labeled human glioblastoma vessels and normal brain vessels provided samples for Affymetrix microarray analyses, which revealed that 95 genes were differentially expressed between the glioblastoma and normal vasculature.

Langenkamp E, Zwiers PJ, Moorlag HE, Leenders WP, St Croix B, and Molema G (2012). Vascular endothelial growth factor receptor 2 inhibition in-vivo affects tumor vasculature in a tumor type-dependent way and downregulates vascular endothelial growth factor receptor 2 protein without a prominent role for miR-296. Anticancer Drugs ; 23: 161-172.

Vandetanib (ZD6474) treatment of mice bearing s.c. LLC or B16.F10 melanoma resulted in a more than 80% reduction in tumor outgrowth. The molecular effects (gene and micro-RNA expression) in the tumor vasculatures associated with these anti-tumor effects were unmasked user lasermicrodissection of the vessels prior to qRT-PCR analysis.

Langenkamp E, vom Hagen FM, Zwiers PJ, Moorlag HE, Schouten JP, Hammes HP, Gouw AS, and Molema G (2011), Tumor Vascular Morphology Undergoes Dramatic Changes during Outgrowth of B16 Melanoma While Proangiogenic Gene Expression Remains Unchanged. ISRN Oncology ePub:article ID 409308.

Sikkema AH, de Bont ES, Molema G, Dimberg A, Zwiers PJ, Diks SH, Hoving EW, Kamps WA, Peppelenbosch MP, and den Dunnen WF (2011). VEGFR-2 signalling activity in paediatric pilocytic astrocytoma is restricted to tumour endothelial cells. Neuropathol Appl Neurobiol; 37(5): 538-548.

Vascular and tissue behavior in disease:

Yan R, van Meurs M, Popa ER, Li R, Zwiers PJ, Zijlstra JG, Moser J, Molema G (2019), Early Heterogenic Response of Renal Microvasculature to Hemorrhagic Shock/Resuscitation and the Influence of NF-κB Pathway Blockade. Shock, 51(2): 200-212

Compartmentalization of kidney blood vessel segments prior to gene expression analysis unmasked heterogeneity in endothelial expression of genes involved in vascular stability/integrity, and segment specific responses to shock conditions and therapeutic intervention.

The editorial by Dr LL Moldawer highlighted the technological advancement of the research presented:  ‘This paper deserves a close read because it is a technological tour de force and its effort to focus on specific structural regions of the kidney. Although NF-κB blockade was not as effective as may have been desirable, the importance of [...] on different kidney regions is an outstanding observation in itself.’ Editorial LL Moldawer on technical advancement and added value of LMD

Asgeirsdottir SA, van SC, Kurniati NF, Zwiers PJ, Heeringa P, van MM, Satchell SC, Saleem MA, Mathieson PW, Banas B, Kamps JA, Rabelink TJ, van Zonneveld AJ, and Molema G (2012), MicroRNA-126 contributes to renal microvascular heterogeneity of VCAM-1 protein expression in acute inflammation. Am J Physiol Renal Physiol, 302(12): F1630-9.

van Meurs M, Fisheri NK, Wulfert FM, Asgeirsdottir SA, de Graaf IA, Satchell SC, Mathieson PW, Jongman RM, Kumpers P, Zijlstra JG, Heeringa P, and Molema G (2009). Shock induced stress induces loss of microvascular endothelial Tie2 in the kidney which is not associated with reduced glomerular barrier function. Am.J Physiol Renal Physiol, 297 (2): F272-281.

Molecular control of microvascular behavior in vivo:

Asgeirsdottir SA, van SC, Kurniati NF, Zwiers PJ, Heeringa P, van MM, Satchell SC, Saleem MA, Mathieson PW, Banas B, Kamps JA, Rabelink TJ, van Zonneveld AJ, and Molema G (2012), MicroRNA-126 contributes to renal microvascular heterogeneity of VCAM-1 protein expression in acute inflammation. Am J Physiol Renal Physiol; 302(12):F1630-9.

Yuan L, Sacharidou A, Stratman AN, Le Bras A, Zwiers PJ, Spokes K, Bhasin M, Shih SC, Nagy JA, Molema G, Aird WC, Davis GE, and Oettgen P (2011). RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG. Blood; 118(4):1145-1153.

Pharmacology:

Yan R, van Meurs M, Popa ER, Li R, Zwiers PJ, Zijlstra JG, Moser J, Molema G (2019), Early Heterogenic Response of Renal Microvasculature to Hemorrhagic Shock/Resuscitation and the Influence of NF-κB Pathway Blockade. Shock, 51(2): 200-212

Compartmentalization of kidney blood vessel segments prior to gene expression analysis unmasked heterogeneity in endothelial expression of genes involved in vascular stability/integrity, and segment specific responses to shock conditions and therapeutic intervention.

The editorial by Dr LL Moldawer highlighted the technological advancement of the research presented:  ‘This paper deserves a close read because it is a technological tour de force and its effort to focus on specific structural regions of the kidney. Although NF-κB blockade was not as effective as may have been desirable, the importance of [...] on different kidney regions is an outstanding observation in itself.’ Editorial LL Moldawer on technical advancement and added value of LMD

Review about the importance of unmasking molecular signatures of cells in complex tissue for drug discovery and drug development:

Langenkamp E, Kamps JA, Mrug M, Verpoorte E, Niyaz Y, Horvatovich P, Bischoff R, Struijker-Boudier H, Molema G (2013). Innovations in studying in vivo cell behaviour and pharmacology in complex tissues - microvascular endothelial cells in the spotlight. Cell Tissue Res, 354(3):647-69.

The review describes how the complexity of in vivo tissues urges us to study cell biology and drug effects in these environments and how the combination of laser microdissection and novel advancements in read out technologies such as proteomics, kinomics and transcriptomics will contribute to a more effective drug development process.