Institut Studium Forschung Leistungen Publikationen Kontakt

Chairman
Principal Investigators
Staff
Career Opportunities
 
lmu_muenchen
Dr.rer.nat. Hanna Mannell

Our group is interested in endothelial physiology and platelet-endothelium interactions leading to thrombus formation. We investigate the role of non-transmembrane tyrosine phosphatases, small guanine exchange factors and receptors of the innate immune system, such as TNFR and TLR, on endothelial processes and signaling important for angiogenesis (proliferation, migration, vessel sprouting) and the development of an endothelial pro-inflammatory phenotype (generation of reactive oxygen species, upregulation of adhesion molecules). An additional focus of our research is also to investigate the influence of these factors on platelet activation, adhesion and thrombus formation.
Within the DFG research unit FOR917 “Nanoguide”, we have also concentrated on the development of a technique enabling site specific vascular gene transfer in vivo. This is accomplished by systemic administration of magnetic microbubbles and their targeting to the vascular wall using an external magnetic field and subsequent ultrasound mediated microbubble rupture for release of the genetic material. The aim is to apply this technique as a scientific tool investigating the role of different signaling molecules important for endothelial functions in vivo.

Contact: hanna.mannell@lrz.uni-muenchen.de
Members of the Mannell Team: 

Gräff Pascal, Cand. med.
Heun Yvonn, MSc
Hupel Georg, cand. med.
Rotter Raffaela, B. Pharm. Sc.
.

Lab Technician:
Mettler Ramona, Dipl. Ing. (FH)

Associated Members:
Gründler Katharina, MSc. (Medical Policlinic LMU, Cardiology)
Krämer Björn, Dr. med. (Medical Policlinic LMU, Cardiology)

Recent publications:

Y. Heun, S. Hildebrand, A. Heidsieck, B. Gleich, M. Anton, J. Pircher, A. Ribeiro, O. Mykhaylyk, D. Eberbeck, D. Wenzel, A. Pfeifer, M. Woernle, F. Krötz, U. Pohl and H. Mannell. Targeting of Magnetic Nanoparticle-coated Microbubbles to the Vascular Wall Empowers Site-specific Lentiviral Gene Delivery in vivo. Theranostics. (2016); Accepted for publication

K. Grundler, R. Rotter, S. Tilley, J. Pircher, T. Czermak, M. Yakac, E. Gaitzsch, S. Massberg, F. Krotz, HY. Sohn, U. Pohl, H. Mannell and BF. Kraemer. The proteasome regulates collagen-induced platelet aggregation via nuclear-factor-kappa-B (NFkB) activation. Thromb Res. 148:15-22 (2016).

O. Chillo, E.C. Kleinert, T. Lautz, M. Lasch, J.I. Pagel, Y. Heun, K. Troidl, S. Fischer, A. Caballero-Martinez, A. Mauer, A.R. Kurz, G. Assmann, M. Rehberg, S.M. Kanse, B. Nieswandt, B. Walzog, C.A. Reichel, H. Mannell, K.T. Preissner, and E. Deindl. Perivascular Mast Cells Govern Shear Stress-Induced Arteriogenesis by Orchestrating Leukocyte Function. Cell Rep. 16:2197-2207 (2016).

P. Blum, J. Pircher, M. Merkle, T. Czermak, A. Ribeiro, H. Mannell, F. Krotz, A. Hennrich, M. Spannagl, S. Koppel, E. Gaitzsch, and M. Wornle. Arterial thrombosis in the context of HCV-associated vascular disease can be prevented by protein C. Cell Mol Immunol (2016).

S.K. Alig, Y. Stampnik, J. Pircher, R. Rotter, E. Gaitzsch, A. Ribeiro, M. Wornle, F. Krotz, and H. Mannell. The Tyrosine Phosphatase SHP-1 Regulates Hypoxia Inducible Factor-1alpha (HIF-1alpha) Protein Levels in Endothelial Cells under Hypoxia. PLoS One. 10:e0121113 (2015).

M. Merkle, J. Pircher, H. Mannell, F. Krotz, P. Blum, T. Czermak, E. Gaitzsch, C. Schneider, S. Koppel, A. Ribeiro, and M. Wornle. LL37 inhibits the inflammatory endothelial response induced by viral or endogenous DNA. J Autoimmun. 65:19-29 (2015)
.
J. Pircher, T. Czermak, M. Merkle, H. Mannell, F. Krotz, A. Ribeiro, V. Vielhauer, J. Nadjiri, E. Gaitzsch, M. Niemeyer, S. Porubsky, H.J. Grone, and M. Wornle. Hepatitis C virus induced endothelial inflammatory response depends on the functional expression of TNFalpha receptor subtype 2. PLoS One. 9:e113351 (2014).

E. Koch, J. Pircher, T. Czermak, E. Gaitzsch, S. Alig, H. Mannell, et al. The Endothelial Tyrosine Phosphatase SHP-1 Plays an Important Role for Vascular Haemostasis in TNFα-Induced Inflammation In Vivo. Mediatorsof Inflammation 2013: 2013:279781 (3013).

H.K. Mannell, J. Pircher, D.I. Chaudhry, S.K. Alig, E.G. Koch, R. Mettler, U. Pohl, and F. Krötz.. ARNO regulates VEGF-dependent tissue responses by stabilizing endothelial VEGFR-2 surface expression. Cardiovasc Res 2012; 93:111-119 (2012).

J. Pircher, M. Merkle, M. Wörnle, A. Ribeiro, T. Czermak, Y. Stampnik, H. Mannell, M. Niemeyer, V. Vielhauer, F. Krötz. Prothrombotic effects of tumor necrosis factor alpha in vivo are amplified by the absence of tnf-alpha receptor subtype 1 and require tnf-alpha receptor subtype 2. Arthritis Res Ther. 2012; 14:R225

J. Pircher, F. Fochler, T. Czermak, H. Mannell, B. Kraemer, M. Wörnle, A. Sparatore, P. Soldato, U. Pohl, F. Krötz. Hydrogen sulfide-releasing aspirin derivative acs14 exerts strong antithrombotic effects in vitro and in vivo. Arterioscler Thromb Vasc Biol. 2012; 32:2884-91

M. Merkle, A. Ribeiro, F. Belling, H. Mannell, F. Krötz, J. Pircher, M. Wörnle. Response of VEGF to activation of viral receptors and TNFα in human mesangial cells. Mol Cell Biochem. 2012; 370:151-61.

H. Mannell, J. Pircher, F. Fochler, Y. Stampnik, T. Rathel, B. Gleich, C. Plank, O. Mykhaylyk, C. Dahmani, M. Wornle, A. Ribeiro, U. Pohl, and F. Krotz. Site directed vascular gene delivery in vivo by ultrasonic destruction of magnetic nanoparticle coated microbubbles. Nanomedicine. 8:1309-1318 (2012).

H. Mannell, J. Pircher, T. Rathel, K. Schilberg, K. Zimmermann, A. Pfeifer, O. Mykhaylyk, B. Gleich, U. Pohl, and F. Krotz. Targeted endothelial gene delivery by ultrasonic destruction of magnetic microbubbles carrying lentiviral vectors. Pharm Res. 29:1282-1294 (2012).

T. Rathel, H. Mannell, J. Pircher, B. Gleich, U. Pohl, and F. Krotz. Magnetic stents retain nanoparticle-bound antirestenotic drugs transported by lipid microbubbles. Pharm Res. 29:1295-1307 (2012).

M. Merkle, A. Ribeiro, S. Koppel, J. Pircher, H. Mannell, M. Roeder, and M. Wornle. TLR3-dependent immune regulatory functions of human mesangial cells. Cell Mol Immunol. 9:334-340 (2012).

J. Pircher, F. Fochler, T. Czermak, H. Mannell, B. Kraemer, M. Wornle, A. Sparatore, P.D. Soldato, U. Pohl, and F. Krotz. Hydrogen Sulfide-Releasing Aspirin Derivative ACS14 Exerts Strong Antithrombotic Effects In Vitro and In Vivo. Arterioscler Thromb Vasc Biol (2012).

M. Merkle, A. Ribeiro, F. Belling, H. Mannell, F. Krotz, J. Pircher, and M. Wornle. Response of VEGF to activation of viral receptors and TNFalpha in human mesangial cells. Mol Cell Biochem. 370:151-161 (2012).

H. Mannell, A. Hammitzsch, R. Mettler, U. Pohl, and F. Krötz. Suppression of DNA-PKcs enhances FGF-2 dependent human endothelial cell proliferation via negative regulation of Akt. Cell Signal. 22:88-96 (2010).

J. Pircher, M. Merkle, M. Wornle, A. Ribeiro, T. Czermak, Y. Stampnik, H. Mannell, M. Niemeyer, V. Vielhauer, and F. Krotz. Prothrombotic effects of tumor necrosis factor alpha in vivo are amplified by the absence of TNF-alpha receptor subtype 1 and require TNF-alpha receptor subtype 2. Arthritis Res Ther. 14:R225 (2012).

F. Krötz, N. Hellwig, M.A. Burkle, S. Lehrer, T. Riexinger, H. Mannell, H.Y. Sohn, V. Klauss, and U. Pohl. A sulfaphenazole-sensitive EDHF opposes platelet-endothelium interactions in vitro and in the hamster microcirculation in vivo. Cardiovasc Res. 85:542-550 (2010).

L. Struthmann, N. Hellwig, J. Pircher, H.Y. Sohn, M.A. Buerkle, V. Klauss, H. Mannell, U. Pohl, and F. Krötz. Prothrombotic effects of diclofenac on arteriolar platelet activation and thrombosis in vivo. J Thromb Haemost. 7:1727-1735 (2009).

H. Mannell, N. Hellwig, T. Gloe, C. Plank, H.Y. Sohn, L. Groesser, B. Walzog, U. Pohl, and F. Krotz. Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo. J Vasc Res. 45:153-163 (2008).

B. Gleich, N. Hellwig, H. Bridell, R. Jurgons, C. Seliger, C. Alexiou, B. Wolf, T. Weyh. Design and evaluation of magnetic fields for nanoparticle drug targeting in cancer. IEEE Transactions on Nanotechnology. 2007; 6:164-170 (2007)E.

F. Krötz, B. Engelbrecht, M.A. Buerkle, F. Bassermann, H. Bridell, T. Gloe, J. Duyster, U. Pohl, and H.Y. Sohn. The tyrosine phosphatase, SHP-1, is a negative regulator of endothelial superoxide formation. J Am Coll Cardiol. 45:1700-1706 (2005).

Reviews / Letters

H. Mannell and F. Krotz. SHP-2 regulates growth factor dependent vascular signalling and function. Mini Rev Med Chem. 14:471-483 (2014).

H. Mannell and F. Krotz. The Role of SHP-2 in Cell Signalling and Human Disease. Current Enzyme Inhibition. 264-272 (2007).

F. Krotz, H.Y. Sohn, and H. Mannell. Letter by Krotz et al Regarding Article, "Improvement of Peripheral Endothelial Dysfunction by Protein Tyrosine Phosphatase Inhibitors in Heart Failure". Circulation. 115:e648 (2007).