Mediators of Thrombo-inflammation

Research interests

Thrombo-inflammation is a complex process which involves players of innate as well as adaptive immunity to participate in close coordination with the coagulation system to mediate inflammation-associated cellular dysfunction. Disease promoting stimuli such as hyperglycemia, genetic risk factors, or thrombophilia trigger inter-cellular cross-talk via cellular and extra-cellular mediators. Coagulation regulators expressed by a wide variety of cells such as endothelial cells, trophoblast cells, immune cells or tissue-resident cells regulate this cross-talk and therefore thrombo-inflammation. Platelets, popularly known for their role in maintaining hemostasis, are increasingly recognized as key regulators of vascular inflammation. Cell-derived extracellular vesicles (EVs) mediate intercellular communication through cargos composed of proteins, lipids, and nucleic acids.

The exact composition of EVs depends on type and state of the originating cell. These cellular cargos can also be present in an unpackaged form (such as cell-free circulating DNA, cfDNA) and mediate the cellular cross talk. Following activation by a wide variety of agonists, platelets and other cell types release a wide range of biologically active substances and EVs. While platelets and EVs are physiologically required during development, they are also involved in vascular complications, such as in pregnancy or renal vascular diseases.

The focus of our research group is to better understand the contributions of these mediators of thrombo-inflammation in such physiological (development) and pathological conditions and establish targeted therapies. Current projects in our group aim at studying the role of platelets and EVs in thrombo-inflammation. We are also interested in elucidating changes in EV composition during inflammation and its functional impact on vascular inflammation. Furthermore, we aim at dissecting the role of platelets and associated coagulation regulators in pregnancy, renal development and vascular complications at the glomerular filtration barrier.

We are employing several mouse models and state of the art techniques such as microfluidics, digital droplet PCR, exosome purification, nanoparticle tracking analysis and unbiased approaches including LC-MS/MS (cooperation: Prof. Ceglarek) and single-cell RNA-seq. Studying the role of thrombo-inflammatory mediators in vascular complications will lay the ground for the identification of new biomarkers and potential therapies.

Five most representative publications

  1. Kohli S, Hoffmann J, Lochmann F, Markmeyer P, Huebner H, Fahlbusch FB, Al-Dabet MM, Gadi I, Manoharan J, Löttge M, Zenclussen AC, Aharon A, Brenner B, Shahzad K, Ruebner M, Isermann B. 2017 p45 NF-E2 regulates syncytiotrophoblast differentiation by post-translational GCM1 modifications in human intrauterine growth restriction. Cell death dis.
  2. Kohli S, Isermann B. 2017. Placental hemostasis and sterile inflammation: New insights into gestational vascular disease. Thromb Res. Suppl 1:S30-S33.
  3. Kohli S, Ranjan S, Hoffmann J, Kashif M, Daniel EA, Al-Dabet MM, Bock F, Nazir S, Huebner H, Mertens PR, Fischer K, Zenclussen AC, Offermanns S, Aharon A, Brenner B, Shahzad K, Ruebner M, Isermann B. 2016. Maternal extracellular vesicles and platelets promote preeeclampsia through inflammasome activation in embryonic trophoblast. Blood. 128(17):2153-2164.
  4. Heinemann ML, Ilmer M, Silva LP, Hawke DH, Recio A, Vorontsova MA, Alt E, Vykoukal J 2014. Benchtop isolation and characterization of functional exosomes by sequential filtration J Chromatogr A. 1371:125-35.
  5. Kohli S, Chhabra A, Jaiswal A, Rustagi Y, Sharma M, Rani V. 2013. Curcumin suppresses gelatinase B mediated norepinephrine induced stress in H9c2 cardiomyocytes. PLos One. 8(10):e76519.

Members

Dr. rer. nat. Shrey Kohli

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Dr. med. Mitja Heinemann
Medical doctor

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Anubhuti Gupta
PhD student

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Kunal Kumar Singh
PhD student

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Ruaa Younis
PhD student

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Phillip Johann
Student assistant

Saikal Shamkeeva

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Thesis or practical work in our research group

​Students interested in completing their thesis or practical work in our research group should please contact ​Dr. rer. nat. Shrey Kohli or Dr. med. Mitja Heinemann.

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04103 Leipzig
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0341 - 97 22200
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0341 - 97 22222
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0341 - 97 22209
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