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Research Interests

Introduction:

Lipids and lipoproteins – role of lipoprotein lipase

In contrast to glucose, lipids such as triacylglycerol (TAG) or cholesterolesters (CE) are not soluble in the blood and are transported in the form of lipoproteins. These micelles consist of an amphiphillic monolayer of phospholipids and free cholesterol in which apolipoproteins are embedded. In the hydrophobic core TAG and CE are found. In the intestine and liver lipids are packaged into lipoproteins and are transported to peripheral tissues such as adipose tissue, heart and muscle. In the bloodstream, lipoprotein lipase (LPL) mediates the release of fatty acids from TAG. While the fatty acids are taken up by underlying tissues, the remaining rather cholesterol-rich remnant particles are cleared by the liver (Williams 2008).

LPL is the central enzyme in vascular TAG and fatty acid metabolism (Merkel 2002; Olivacrona 2010). A defect in its gene leads to a severe hypertriglyceridemia with pancreatitis as clinical consequence in humans.

Role of LPL in tumor biology

Growing tumors secrete pro-inflammatory cytokines like IL-6 and TNFalpha. These cytokines down-regulate the expression and activity of LPL in peripheral tissues. As LPL is crucial for lipid uptake, decreasing its activity results in a marked caloric deficit in adipose tissue, muscle and heart. The consequence is a massive loss of muscle and fat mass which ultimately leads to cachexia. On the other hand, reports found a link between high expression of LPL by non-small cell lung cancer tumor cells and a shorter patient survival (Trost 2009). The same correlation of high LPL expression and poor clinical outcome was found in chronic lymphocytic leukemia (Heintel 2005; Oppezzo 2005). Taken together, these studies suggest an important role for LPL in tumor development and associated cachexia as it delivers energy for tumor growth while it steals energy from peripheral tissues.

Development of an in vivo sensor for lipoprotein lipase activity based on nanocrystals

Here, I am planing to develop an in vivo sensor for LPL activity based on nanocrystals.

A recombinant lipoprotein model named nanosomes which carries different species of nanocrystals was recently established (Bruns et al. Nature Nanotechnology 2009, Bartelt et al. Nature Medicine 2011). Given the high flexibility and exceptional signal properties, nanosomes will be used as the platform for the LPL sensor.

 

Publications:

Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, Kaul MG, Tromsdorf UI, Weller H, Waurisch C, Eychmüller A, Gordts PLSM, Rinninger F, Bruegelmann K, Freund B, Nielsen P, Merkel M and Heeren J, Brown adipose tissue activity controls triglyceride clearance. Nature Medicine, 2011 Feb;17(2):200-5.

Heeren J, Bruns OT, Nanocrystals, a new tool to study lipoprotein metabolism and atherosclerosis. Current Pharmaceutical Biotechnology, 2011 Apr 6. [Epub ahead of print]

Mangerich A, Herbach N, Hanf B, Fischbach A, Popp O, Moreno-Villanueva M, Bruns OT, Bürkle A. Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1. Mechanisms of Ageing and Development, 2010 Jun;131(6):389-404.

Tromsdorf UI, Bruns OT, Salmen S, Beisiegel U and Weller H, A highly effective, nontoxic T1 MR contrast agent based on ultrasmall PEGylated iron oxide nanoparticles. Nano Letters, 2009 Dec;9(12):4434-40.

Bruns OT, Ittrich H, Peldschus K, Kaul MG, Tromsdorf UI, Lauterwasser J, Nikolic MS, Mollwitz B, Merkel M, Bigall NC, Sapra S, Reimer R, Hohenberg H, Weller H, Eychmüller A, Adam G, Beisiegel U, Heeren J, Real-time magnetic resonance imaging and quantification of lipoprotein metabolism in vivo using nanocrystals. Nature Nanotechnology, 2009 Mar;4(3):193-201.

Muñoz Javier A, Kreft O, Semmling M, Kempter S, Skirtach AG, Bruns OT, del Pino P, Bedard M, Rädler J, Käs J, Plank C, Sukhorukov GB, Parak WJ, Uptake of colloidal polyelectrolyte coated particles and polyelectrolyte multilayer capsules by living cells. Advanced Materials, 2008 Nov; 20 (22): 4281-7.

Tromsdorf UI, Bigall NC, Kaul MG, Bruns OT, Nikolic MS, Mollwitz B, Sperling RA, Reimer R, Hohenberg H, Parak WJ, Förster S, Beisiegel U, Adam G and Weller H, Size and Surface Effects on the MRI Relaxivity of Manganese Ferrite Nanoparticle Contrast Agents. Nano Letters, 2007 Aug;7(8):2422-7.

Perbandt M, Bruns O, Vallazza M, Lamla T, Betzel C and Erdmann VA, High resolution structure of streptavidin in complex with a novel high affinity peptide tag mimicking the biotin binding motif. Proteins, 2007 Jun 1;67(4):1147-53.

Redecke L, von Bergen M, Clos J, Konarev PV, Svergund DI, Fittschen UE, Broekaert JA, Bruns O, Georgieva D, Mandelkow E, Genov N, and Betzel C, Structural characterization of beta-sheeted oligomers formed on the pathway of oxidative prion protein aggregation in vitro. Journal of Structural Biology, 2007 Feb;157(2):308-20.

Boldt K, Bruns OT, Gaponik N, and Eychmuller A, Comparative Examination of the Stability of Semiconductor Quantum Dots in Various Biochemical Buffers. Journal of Physical Chemistry B, 2006 Feb, 110(5), 1959-63.

Awards

2006-2009 Fellowship by ‘Studienstiftung des Deutschen Volkes’ (German National Academic Foundation)
2006 Award for the best diploma thesis in Biochemistry/Molecular Biology
2007 Young Investigator Award, 30th annual Meeting of European Lipoprotein Club, Tutzing, Germany
2008 Young Investigator Award, 77th European Atherosclerosis Congress, 2008, Istanbul, Turkey
2010 Karl-Heinz Hölzer PhD-Award for Interdisciplinary Medical Research
2011 EMBO Long-Term Fellowship

 

Selected publications

Carr JA, Valdez T, Bruns OT, Bawendi MG. Using the shortwave infrared to image middle ear pathologies. Proceedings of the National Academy of Sciences of the United States of America. 2016, 113, No. 36, 9989–9994.

Franke D, Harris DK, Chen O, Bruns OT, Carr JA, Wilson MWB, Bawendi MG. Continuous injection synthesis of indium arsenide quantum dots emissive in the short-wavelength infrared. Nature Communications. 2016, , 12749.

Rowlands CJ, Bruns OT, Bawendi MG, So PTC. Objective, comparative assessment of the penetration depth of temporal-focusing microscopy for imaging various organs. Journal of Biomedical Optics. 2015, 20, 061107.

Lemon CM, Karnas E, Han X, Bruns OT, Kempa TJ, Fukumura D, Bawendi MG, Jain RK, Duda DG, Nocera DG.. Micelle-Encapsulated Quantum Dot-Porphyrin Assemblies as in Vivo Two-Photon Oxygen Sensors. Journal of the American Chemical Society. 2015, 137 , 9832–9842.

Chen O, Riedemann L, Etoc F, Herrmann H, Coppey M, Barch M, Farrar CT, Zhao J, Bruns OT, Wei H, Guo P, Cui J, Jensen R, Chen Y, Harris DK, Cordero JM, Wang Z, Jasanoff A, Fukumura D, Reimer R, Dahan M, Jain RK, Bawendi MG. Magneto-fluorescent core-shell supernanoparticles. Nature Communications. 2014, 5, 5093.

Wei H, Bruns OT, Chen O, Bawendi MG. Compact zwitterion-coated iron oxide nanoparticles for in vitro and in vivo imaging. Integrative Biology. 2013, 5, 108-114.