Selected Publications


ENDOTHELIAL (DYS)FUNCTION

 

Yuan L., Chan G.C., Beeler D., Janes L., Spokes K.C., Dharaneeswaran H., Mojiri A., Adams W.J., Sciuto T., Garcia-Cardeña G., Molema G., Kang P.M., Jahroudi N., Marsden P.A., Dvorak A., Regan E.R., Aird W.C. A role of stochastic phenotype switching in generating mosaic endothelial cell heterogeneity. Nat Commun 2016; 7: 10160.

 

Raj, D.D., Moser, J., van der Pol, S.M., van Os, R.P., Holtman, I.R., Brouwer, N., Oeseburg, H., Schaafsma, W., Wesseling, E.M., den Dunnen, W., Biber, K.P., de Vries, H.E., Eggen, B.J., Boddeke, H.W. Enhanced microglial pro-inflammatory response to lipopolysaccharide correlates with brain infiltration and blood-brain barrier dysregulation in a mouse model of telomere shortening. Aging Cell 2015; 14: 1003–13.

 

Iovino F., Molema G., Bijlsma J.J. Platelet endothelial cell adhesion molecule-1, a putative receptor for the adhesion of Streptococcus pneumoniae to the vascular endothelium of the blood-brain barrier. Infect Immun. 2014; 82(9):3555-66.

 

Dickinson M.G., Kowalski P.S., Bartelds B., Borgdorff M.A., van der Feen D., Sietsma H., Molema G., Kamps J.A., Berger R.M. A critical role for Egr-1 during vascular remodelling in pulmonary arterial hypertension. Cardiovasc Res. 2014; 103(4): 573-84.

 

Molema G. Heterogeneity in endothelial responsiveness to cytokines, molecular causes and pharmacological consequences. Sem Thromb Hemost. 2010; 36: 246-264.

SHOCK RESEARCH

 

Moser, J., Heeringa, P., Jongman, R.M., Zwiers, P., Niemarkt, A., de Graaf, I.A., Li, R., Regan, E.R., Kümpers, P., Aird, W.C., van Nieuw Amerongen, G.P., Zijlstra, J.G., Molema, G., van Meurs, M. Intracellular RIG-I signalling regulates TLR4-independent endothelial inflammatory responses to endotoxin. J Immunol 2016; 196:4681-91.

 

Zonneveld R., Molema G., Plötz F.B. Measurement of functional and morphodynamic neutrophil phenotypes in systemic inflammation and sepsis. Crit Care. 2016; 24; 20:235.

 

Zonneveld R., Molema G., Plötz F.B. Analyzing Neutrophil Morphology, Mechanics, and Motility in Sepsis: Options and Challenges for Novel Bedside Technologies. Crit Care Med. 2016; 44(1): 218-28.

 

Li, R., Aslan, A., Yan, R., Jongman, R.M., Moser, J., Zwiers, P.J., Moorlag, H.E., Zijlstra, J.G., Molema, G., van Meurs, M. Histone Deacetylase Inhibition and IκB Kinase/Nuclear Factor-κB Blockade Ameliorate Microvascular Proinflammatory Responses Associated With Hemorrhagic Shock/Resuscitation in Mice. Crit Care Med 2015; 43: e567-80.

 

Li R., Zijlstra J.G., Kamps J.A., van Meurs M., Molema G. Abrupt reflow enhances cytokine-induced proinflammatory activation of endothelial cells during simulated shock and resuscitation. Shock 2014; 42(4):356-64.

 

Aslan, A., Jongman, R.J., Moser, J., Stegeman, C.A., Diepstra, A., van Goor, H., Molema, G., Heeringa, P., Zijlstra, J.G., van Meurs, M. Renal Angiopoietins in lethal human sepsis. Crit Care 2014; 18: 423. PMID:24976393 DOI:10.1186/cc13806

 

Jongman, R.M., Zijlstra, J.G., Mariani, M.A., Moser, J., Struys, M.M.R.F., Ligtenberg, J.J.M., Absalom, A.A.R., Molema, G., Scheeren, T.W.L., van Meurs, M. Off-pump CABG surgery reduces systemic inflammation compared to on-pump CABG but does not change endothelial responses: a randomized clinical study. Shock 2014; 42: 121-8.

 

Kurniati N.F., Jongman R.M., vom Hagen F., Spokes K.C., Moser J., Regan E.R., Krenning G., Moonen J.R., Harmsen M.C., Struys M.M., Hammes H.P., Zijlstra J.G., Aird W.C., Heeringa P., Molema G., van Meurs M. The flow dependency of Tie2 expression in endotoxemia. Intensive Care Med 2013;39:1262-71.

 

Kurniati N.F., van Meurs M., vom Hagen F., Jongman R.M., Moser J., Zwiers P.J., Struys M.M., Westra J., Zijlstra J.G., Hammes H.P., Molema G., Heeringa P. Pleiotropic effects of angiopoietin-2 deficiency do not protect mice against endotoxin-induced acute kidney injury. Nephrol Dial Transplant 2013;28:567-75.

 

Asgeirsdottir S.A., van Solingen C., Kurniati N.F., Zwiers P.J., Heeringa P., van Meurs M., Satchell S.C., Saleem M.A., Mathieson P.W., Banas B., Kamps J.A.A.M., Rabelink T.J., van Zonneveld A.J., and Molema G. MicroRNA-126 contributes to renal microvascular heterogeneity of VCAM-1 protein expression in acute inflammation. Am J Physiol Renal Physiol 2012; 302:F1630–F1639.

 

Wulfert F.M., van Meurs M., Kurniati N.F., Jongman R.M., Houwertjes M.C., Heeringa P., Struys M.M., Zijlstra J.G., Molema G. Age-dependent Role of Microvascular Endothelial and Polymorphonuclear Cells in Lipopolysaccharide-induced Acute Kidney Failure. Anesthesiology 2012; 117: 126-36.

 

van Meurs M., Wulfert F.M., Knol A.J., De Haes A., Houwertjes M., Aarts L.P., Molema G. Early organ-specific endothelial activation during hemorrhagic shock and resuscitation. Shock 2008; 29: 291-9.

TARGETED DRUG DELIVERY

 

 Visweswaran G.R., Gholizadeh S., Ruiters M.H., Molema G., Kok R.J., Kamps J.A. Targeting rapamycin to podocytes using a vascular cell adhesion molecule-1 (VCAM-1)-harnessed SAINT-based lipid carrier system. PLoS One. 2015; 10(9): e0138870.

 

Kowalski P.S., Kuninty P.R., Bijlsma K.T., Stuart M.C., Leus N.G., Ruiters M.H., Molema G., Kamps J.A. SAINT-Liposome-Polycation particles, a new carrier for improved delivery of siRNAs to inflamed endothelial cells. Eur J Pharm Biopharm. 2015; 89: 40-7.

 

Leus N.G., Morselt H.W., Zwiers P.J., Kowalski P.S., Ruiters M.H., Molema G., Kamps J.A. VCAM-1 specific PEGylated SAINT-based lipoplexes deliver siRNA to activated endothelium in vivo but do not attenuate target gene expression. Int J Pharm. 2014; 469(1): 121-31.

 

Kowalski P.S., Zwiers P.J., Morselt H.W., Kuldo J.M., Leus N.G., Ruiters M.H., Molema G., Kamps J.A. Anti-VCAM-1 SAINT-O-Somes enable endothelial-specific delivery of siRNA and downregulation of inflammatory genes in activated endothelium in vivo. J. Control. Rel. 2014; 176: 64–75

 

Leus N.G., Talman E.G., Ramana P., Kowalski P.S., Woudenberg-Vrenken T.E., Ruiters M.H., Molema G., Kamps J.A. Effective siRNA delivery to inflamed primary vascular endothelial cells by anti-E-selectin and anti-VCAM-1 PEGylated SAINT-based lipoplexes. Int J Pharm. 2014; 459(1-2): 40-50.

 

Kowalski P.S., Lintermans L.L., Morselt H.W., Leus N.G., Ruiters M.H., Molema G., Kamps J.A. Anti-VCAM-1 and anti-E-selectin SAINT-O-Somes for selective delivery of siRNA into inflammation-activated primary endothelial cells. Mol Pharm. 2013; 10(8): 3033-44.

 

Kułdo J.M., Asgeirsdóttir S.A., Zwiers P.J., Bellu A.R., Rots M.G., Schalk J.A., Ogawara K.I., Trautwein C., Banas B., Haisma H.J., Molema G., Kamps J.A. Targeted adenovirus mediated inhibition of NF-κB-dependent inflammatory gene expression in endothelial cells in vitro and in vivo. J Control Release. 2013; 166(1): 57-65.

 

Adrian J.E., Morselt H.W., Süss R., Barnert S., Kok J.W., Asgeirsdóttir S.A., Ruiters M.H., Molema G., Kamps J.A. Targeted SAINT-O-Somes for improved intracellular delivery of siRNA and cytotoxic drugs into endothelial cells. J Control Release. 2010; 144(3): 341-9.

 VASCULITIS RESEARCH

 

Wang Q., van Timmeren M.M., Petersen A.H., Yuan J., Moser J., Brouwer E., Westra J., Boots A.M., Heeringa P. Age-determined severity of anti-myeloperoxidase autoantibody-mediated glomerulonephritis in mice. Nephrol Dial Transplant. 2016; pii: gfw202.

 

O'Reilly V.P., Wong L., Kennedy C., Elliot L.A., O'Meachair S., Coughlan A.M., O'Brien E.C., Ryan M.M., Sandoval D., Connolly E., Dekkema G.J., Lau J., Abdulahad W.H., Sanders J.S., Heeringa P., Buckley C., O'Brien C., Finn S., Cohen C.D., Lindemeyer M.T., Hickey F.B., O'Hara P.V., Feighery C., Moran S.M., Mellotte G., Clarkson M.R., Dorman A.J., Murray P.T., Little M.A. Urinary Soluble CD163 in Active Renal Vasculitis. J Am Soc Nephrol. 2016; 27(9): 2906-16.

 

Lepse N., Land J, Rutgers A., Kallenberg C.G., Stegeman C.A., Abdulahad W.H., Heeringa P. Toll-like receptor 9 activation enhances B cell activating factor and interleukin-21 induced anti-proteinase 3 autoantibody production in vitro. Rheumatology 2016; 55(1): 162-72.

 

Lepse N., Abdulahad W.H., Rutgers A., Kallenberg C.G., Stegeman C.A., Heeringa P. Altered B cell balance, but unaffected B cell capacity to limit monocyte activation in anti-neutrophil cytoplasmic antibody-associated vasculitis in remission. Rheumatology 2014 ; 53(9): 1683-92.

 

Kallenberg C.G., Stegeman C.A., Abdulahad W.H., Heeringa P. Pathogenesis of ANCA-associated vasculitis: new possibilities for intervention. Am J Kidney Dis. 2013; 62(6): 1176-87.

 

Roth A.J., Ooi J.D., Hess J.J., van Timmeren M.M., Berg E.A., Poulton C.E., McGregor J., Burkart M., Hogan S.L., Hu Y., Winnik W., Nachman P.H., Stegeman C.A., Niles J., Heeringa P., Kitching A.R., Holdsworth S., Jennette J.C., Preston G.A., Falk R.J. Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis. J Clin Invest. 2013; 123(4): 1773-83.

 

van Timmeren M.M., van der Veen B.S., Stegeman C.A., Petersen A.H., Hellmark T., Collin M., Heeringa P. IgG glycan hydrolysis attenuates ANCA-mediated glomerulonephritis. J Am Soc Nephrol. 2010; 21(7): 1103-14.

 

Huugen D., van Esch A., Xiao H., Peutz-Kootstra C.J., Buurman W.A., Tervaert J.W., Jennette J.C., Heeringa P. Inhibition of complement factor C5 protects against anti-myeloperoxidase antibody-mediated glomerulonephritis in mice. Kidney Int. 2007; 71(7): 646-54.

 

Huugen D., Xiao H., van Esch A., Falk R.J., Peutz-Kootstra C.J., Buurman W.A., Tervaert J.W., Jennette J.C., Heeringa P. Aggravation of anti-myeloperoxidase antibody-induced glomerulonephritis by bacterial lipopolysaccharide: role of tumor necrosis factor-alpha. Am J Pathol. 2005; 167(1): 47-58.

 

Xiao H., Heeringa P., Hu P., Liu Z., Zhao M., Aratani Y., Maeda N., Falk R.J., Jennette J.C. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest. 2002; 110(7): 955-63.

ONCOLOGY

 

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

 

van der Wal G.E., Gouw A.S., Kamps J.A., Moorlag H.E., Bulthuis M.L., Molema G., de Jong K.P. Angiogenesis in synchronous and metachronous colorectal liver metastases: the liver as a permissive soil. Ann Surg. 2012; 255: 86-94.

 

Langenkamp E., Zwiers P.J., Moorlag H.E., Leenders W.P., St Croix B., Molema G. 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. 2012; 23: 161-72

 

Langenkamp E., vom Hagen F.M., Zwiers P.J., Moorlag H.E., Schouten J.P., Hammes H.P., Gouw A.S., Molema G. Tumor Vascular Morphology Undergoes Dramatic Changes during Outgrowth of B16 Melanoma While Proangiogenic Gene Expression Remains Unchanged. ISRN Oncology 2011.

Ingrid (G.) Molema

Professor of Life Sciences / EBVDT Group Leader

University Medical Center Groningen (UMCG)

Dept. Pathology and Medical Biology, Medical Biology section

 

Room T2.228

Internal postal code: EA11

Hanzeplein 1

9713 GZ Groningen

The Netherlands

Telephone: +31-50-3610115

Fax: +31-50-3619911

Email: g.molema01@umcg.nl

 

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