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                                                  Yaw Asare – Experimental Atherosclerosis Research

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                                                  From GWAS discovery to mechanisms and therapeutic targeting

                                                  Experimental Atherosclerosis Research – Yaw Asare

                                                  Experimental Atherosclerosis Research Focus

                                                  We are interested in the cellular and molecular mechanisms underlying atherosclerotic cardiovascular disease with an overarching aim of understanding disease initiation and progression. We strive to identify novel therapeutic targets and cell-type specific mechanisms through a wide range of cellular and molecular biology techniques, cutting-edge multi-omics approaches, in vitro and cellular assays, and transgenic animal models.

                                                  Drug targets supported by human genetics have a higher probability of reaching phase III clinical trials and regulatory approval. Genome-wide association studies (GWAS) have identified novel risk loci for large artery atherosclerotic stroke most of which reside in intronic and intergenic regions with gene regulatory function. We determine causality of relevant genes in animal models of vascular inflammation and atherosclerosis, scrutinize the mechanisms linking them to atherosclerosis, and explore therapeutic targeting strategies for vascular protection. We have a particular interest in elucidating inflammatory pathways with central roles in the pathogenesis of atherosclerosis (e.g. NF-κB & NLRP3 inflammasome signaling), which we identified as downstream effectors of risk loci with relevance for human atherosclerosis.

                                                  Another focus is the uptake and transcytosis of LDL across the atherogenic vascular endothelium and intracellular processing by macrophages. We have particular interest in understanding how scavenger receptors orchestrate this step in atherogenesis and the downstream signaling network induced upon ligand-receptor binding.

                                                  Yaw Asare

                                                  Contact: Yaw Asare

                                                  Tel: +49-89-4400-46170

                                                  yaw.asare@med.uni-muenchen.de

                                                  Publications by Yaw Asare

                                                  Asare Y*, Shnipova M, Živković L, Schlegl C, Tosato F, Aronova A, Brandhofer M, Strohm L, Beaufort N, Malik R, Weber C, Bernhagen J, Dichgans M*. IKKβ binds NLRP3 providing a shortcut to inflammasome activation for rapid immune responses. Signal Transduct Target Ther. 2022 Oct 19;7(1):355. doi: 10.1038/s41392-022-01189-3. (*corresponding authors)

                                                  Živković L, Asare Y, Bernhagen J, Dichgans M, Georgakis MK. Pharmacological Targeting of the CCL2/CCR2 Axis for Atheroprotection: A Meta-Analysis of Preclinical Studies. Arterioscler Thromb Vasc Biol. 2022 May;42(5):e131-e144. doi: 10.1161/ATVBAHA.122.317492. Epub 2022 Apr 7. PMID: 35387476.

                                                  Georgakis MK, van der Laan SW, Asare Y, Mekke JM, Haitjema S, Schoneveld AH, de Jager SCA, Nurmohamed NS, Kroon J, Stroes ESG, de Kleijn DPV, de Borst GJ, Maegdefessel L, Soehnlein O, Pasterkamp G, Dichgans M. Monocyte-Chemoattractant Protein-1 Levels in Human Atherosclerotic Lesions Associate With Plaque Vulnerability. Arterioscler Thromb Vasc Biol. 2021 Jun;41(6):2038-2048. doi: 10.1161/ATVBAHA.121.316091. Epub 2021 Apr 8. PMID: 33827260.

                                                  Roth S, Cao J, Singh V, Tiedt S, Hundeshagen G, Li T, Boehme JD, Chauhan D, Zhu J, Ricci A, Gorka O, Asare Y, Yang J, Lopez MS, Rehberg M, Bruder D, Zhang S, Groß O, Dichgans M, Hornung V, Liesz A. Post-injury immunosuppression and secondary infections are caused by an AIM2 inflammasome-driven signaling cascade. Immunity. 2021 Apr 13;54(4):648-659.e8. doi: 10.1016/j.immuni.2021.02.004. Epub 2021 Mar 4. 

                                                  Asare Y, Campbell-James TA, Bokov Y, Yu LL, Prestel M, El Bounkari O, Roth S, Megens RTA, Straub T, Thomas K, Yan G, Schneider M, Ziesch N, Tiedt S, Silvestre-Roig C, Braster Q, Huang Y, Schneider M, Malik R, Haffner C, Liesz A, Soehnlein O, Bernhagen J, Dichgans M. Histone Deacetylase 9 Activates IKK to Regulate Atherosclerotic Plaque Vulnerability. Circ Res. 2020 Aug 28;127(6):811-823. doi: 10.1161/CIRCRESAHA.120.316743. Epub 2020 Jun 17. 

                                                  Asare Y, Koehncke J, Selle J, Simsekyilmaz S, Jankowski J, Shagdarsuren G, Gessner JE, Bernhagen J, Shagdarsuren E. Differential Role for Activating FcγRIII in Neointima Formation After Arterial Injury and Diet-Induced Chronic Atherosclerosis in Apolipoprotein E-Deficient Mice. Front Physiol. 2020 Jun 17;11:673. doi: 10.3389/fphys.2020.00673. 

                                                  Kontos C, El Bounkari O, Krammer C, Sinitski D, Hille K, Zan C, Yan G, Wang S, Gao Y, Brandhofer M, Megens RTA, Hoffmann A, Pauli J, Asare Y, Gerra S, Bourilhon P, Leng L, Eckstein HH, Kempf WE, Pelisek J, Gokce O, Maegdefessel L, Bucala R, Dichgans M, Weber C, Kapurniotu A*, Bernhagen J*. Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting. Nat Commun. 2020 Nov 25;11(1):5981. doi: 10.1038/s41467-020-19764-z. PMID: 33239628; PMCID: PMC7689490.

                                                  Tilstam PV, Soppert J, Hemmers C, Harlacher E, Döring Y, van der Vorst EPC, Schulte C, Alampour-Rajabi S, Theelen W, Asare Y, de Winther MPJ, Lawrence T, Bernhagen J, Schober A, Zernecke A, Jankowski J, Weber C, Noels H. Non-activatable mutant of inhibitor of kappa B kinase α (IKKα) exerts vascular site-specific effects on atherosclerosis in Apoe-deficient mice. Atherosclerosis. 2020 Jan;292:23-30. doi: 10.1016/j.atherosclerosis.2019.10.023. Epub 2019 Nov 2. 

                                                  Sinitski D, Kontos C, Krammer C, Asare Y, Kapurniotu A, Bernhagen J. Macrophage Migration Inhibitory Factor (MIF)-Based Therapeutic Concepts in Atherosclerosis and Inflammation. Thromb Haemost. 2019 Apr;119(4):553-566. doi: 10.1055/s-0039-1677803. Epub 2019 Feb 4. 

                                                  Prestel M, Prell-Schicker C, Webb T, Malik R, Lindner B, Ziesch N, Rex-Haffner M, Röh S, Viturawong T, Lehm M, Mokry M, den Ruijter H, Haitjema S, Asare Y, Söllner F, Najafabadi MG, Aherrahrou R, Civelek M, Samani NJ, Mann M, Haffner C, Dichgans M. The Atherosclerosis Risk Variant rs2107595 Mediates Allele-Specific Transcriptional Regulation of HDAC9 via E2F3 and Rb1. Stroke. 2019

                                                  Klasen C, Ziehm T, Huber M, Asare Y, Kapurniotu A, Shachar I, Bernhagen J, El Bounkari O. LPS-mediated cell surface expression of CD74 promotes the proliferation of B cells in response to MIF. Cell Signal. 2018 Jun;46:32-42. doi: 10.1016/j.cellsig.2018.02.010. Epub 2018 Feb 21. 

                                                  Asare Y, Ommer M, Azombo FA, Alampour-Rajabi S, Sternkopf M, Sanati M, Gijbels MJ, Schmitz C, Sinitski D, Tilstam PV, Lue H, Gessner A, Lange D, Schmid JA, Weber C, Dichgans M, Jankowski J, Pardi R, de Winther MP, Noels H, Bernhagen J. Inhibition of atherogenesis by the COP9 signalosome subunit 5 in vivo. Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):E2766-E2775. doi: 10.1073/pnas.1618411114. Epub 2017 Mar 14. 

                                                  van der Vorst EPC, Maas SL, Ortega-Gomez A, Hameleers JMM, Bianchini M, Asare Y, Soehnlein O, Döring Y, Weber C, Megens RTA. Functional ex-vivo Imaging of Arterial Cellular Recruitment and Lipid Extravasation. Bio Protoc. 2017 Jun 20;7(12):e2344. doi: 10.21769/BioProtoc.2344. 

                                                  Jumpertz S, Hennes T, Asare Y, Schütz AK, Bernhagen J. CSN5/JAB1 suppresses the WNT inhibitor DKK1 in colorectal cancer cells. Cell Signal. 2017 Jun;34:38-46. doi: 10.1016/j.cellsig.2017.02.013. Epub 2017 Feb 14. 

                                                  Asare Y, Vijayan S, Shagdarsuren G, Shagdarsuren E. Complement Blocking Therapeutic Strategies: A Prospective Approach for the Treatment of Cardiovascular Diseases. Frontiers in Cardiovascular Drug Discovery 2016, Vol 3 (Book Chapter)

                                                  Selle J, Asare Y, Köhncke J, Alampour-Rajabi S, Shagdarsuren G, Klos A, Weber C, Jankowski J, Shagdarsuren E. Atheroprotective role of C5ar2 deficiency in apolipoprotein E-deficient mice. Thromb Haemost. 2015 Oct;114(4):848-58. doi: 10.1160/TH14-12-1075. Epub 2015 Jun 18. 

                                                  Salem S, Jankowski V, Asare Y, Liehn E, Welker P, Raya-Bermudez A, Pineda-Martos C, Rodriguez M, Muñoz-Castañeda JR, Bruck H, Marx N, Machado FB, Staudt M, Heinze G, Zidek W, Jankowski J. Identification of the Vasoconstriction-Inhibiting Factor (VIF), a Potent Endogenous Cofactor of Angiotensin II Acting on the Angiotensin II Type 2 Receptor. Circulation. 2015 Apr 21;131(16):1426-34. doi: 10.1161/CIRCULATIONAHA.114.013168. Epub 2015 Mar 25. 

                                                  Vijayan S*, Asare Y* , Grommes J, Soehnlein O, Lutgens E, Shagdarsuren G, Togtokh A, Jacobs M, Fischer J.W , Bernhagen J, Weber C, Schober A, Shagdarsuren E. High Expression of C5L2 Correlates with High Pro-inflammatory Cytokine Expression in Advanced Human Atherosclerotic Plaque. Am J Pathol. 2014 (* shared first authorship)

                                                  Jumpertz S, Hennes T, Asare Y, Vervoorts J, Bernhagen J, Schütz AK. The β-catenin E3 ubiquitin ligase SIAH-1 is regulated by CSN5/JAB1 in CRC cells. Cell Signal. 2014 Sep;26(9):2051-9. doi: 10.1016/j.cellsig.2014.05.013. Epub 2014 May 29. 

                                                  Tilstam PV, Gijbels MJ, Habbeddine M, Cudejko C, Asare Y, Theelen W, Zhou B, Döring Y, Drechsler M, Pawig L, Simsekyilmaz S, Koenen RR, de Winther MP, Lawrence T, Bernhagen J, Zernecke A, Weber C, Noels H. Bone marrow-specific knock-in of a non-activatable Ikkα kinase mutant influences haematopoiesis but not atherosclerosis in Apoe-deficient mice. PLoS One. 2014 Feb 3;9(2):e87452. doi: 10.1371/journal.pone.0087452. 

                                                  Asare Y, Shagdarsuren E, Schmid JA, Tilstam PV, Grommes J, El Bounkari O, Schütz AK, Weber C, de Winther MP, Noels H, Bernhagen J. Endothelial CSN5 impairs NF-κB activation and monocyte adhesion to endothelial cells and is highly expressed in human atherosclerotic lesions. Thromb Haemost. 2013 Jul;110(1):141-52. doi: 10.1160/TH13-02-0155. Epub 2013 May 2. 

                                                  Asare Y, Schmitt M, Bernhagen J. The vascular biology of macrophage migration inhibitory factor (MIF). Expression and effects in inflammation, atherogenesis and angiogenesis. Thromb Haemost. 2013 Mar;109(3):391-8. doi: 10.1160/TH12-11-0831. Epub 2013 Jan 17. 

                                                  Kanzler I, Tuchscheerer N, Steffens G, Simsekyilmaz S, Konschalla S, Kroh A, Simons D, Asare Y, Schober A, Bucala R, Weber C, Bernhagen J, Liehn EA. Differential roles of angiogenic chemokines in endothelial progenitor cell-induced angiogenesis. Basic Res Cardiol. 2013 Jan;108(1):310. doi: 10.1007/s00395-012-0310-4. Epub 2012 Nov 9. 

                                                  Support for Experimental Atherosclerosis Research

                                                  We gratefully acknowledge support for our work by the following funding agencies:

                                                  DFG Deutsche Forschungsgemeinschaft

                                                  CRC1123/3 [Project B3]: Yaw Asare / Martin Dichgans – Mechanistic role of HDAC9 in atherosclerosis

                                                  Jul 2018 – Jun 2026

                                                  FöFoLe

                                                  Excellence program for research and funding (FöFoLe, LMU)

                                                  Nov 2015 – May 2017

                                                  Friedrich-Bauer-Stiftung

                                                  Friedrich-Baur-Stiftung (LMU)

                                                  2017 & 2020

                                                  Atherosclerosis Research Team

                                                  Yaw Asare, Team Leader

                                                  Arailym Aronova, PhD student

                                                  Federica Tosato, PhD student

                                                  Christina Schlegl, MD student

                                                  Luka Zivkovic, MD student

                                                  Margarita Shnipova, MSc student

                                                  Yaw Asare CV

                                                  Yaw Asare, PhD

                                                  Originally from Ghana, I studied biochemistry, biomedical engineering, and vascular biology. My research ambition is twofold: 1) understand inflammatory mechanisms in atherosclerosis as a major cause of ischemic stroke; and 2) identify novel druggable targets for vascular protection (Asare et al. Circ Res 2020; Asare et al. PNAS 2017). This is an effort guided by human genetics and we pursue it from basic science to preclinical translation.

                                                  Guest Editor (Cells) 

                                                  Special Issue "Vascular Inflammation and Atherosclerosis: From Basic Mechanisms to Therapeutic Opportunities" >>


                                                  Scientific Vita

                                                  01/2022
                                                  Team Leader, Experimental Atherosclerosis Research, Institute for Stroke and Dementia Research, LMU Hospital, Munich Germany

                                                  09/2014 –12/2021
                                                  Postdoctoral Investigator & Senior Scientist, Institute for Stroke and Dementia Research, LMU Hospital, Munich Germany

                                                  10/2012 – 08/2014
                                                  Postdoctoral Investigator with shared affiliation at Institute of Biochemistry and Molecular Cell Biology & Institute for Molecular Cardiovascular Research, both RWTH Aachen University Hospital

                                                  09/2012
                                                  PhD thesis "Role of COP9 Signalosome and IKK complex in Atherosclerosis", Center for Biochemistry, RWTH Aachen University, Germany (Prof. Dr. J. Bernhagen)

                                                  2006 – 2008 MSc Biomedical Engineering, RWTH Aachen University, Germany

                                                  2001 – 2005
                                                  BSc Biochemistry, KNUST, Kumasi, Ghana


                                                  Honors & Awards

                                                  • Finalist Young Investigator Award of the German Society for Microcirculation and Vascular Biology (2017)
                                                  • BRAIN & BRAIN PET Early Career Investigator Travel Award (2017)
                                                  • European Vascular Biology Organization (EVBO) Travel Award (2012)
                                                  • European Society for Microcirculation (ESM) Travel Award (2011)
                                                  • Signal Transduction Society (STS) Travel Award (2011 & 2009)
                                                  • PhD scholarship from the German Research Foundation (2008)
                                                  • GARG Foundation Scholarship (2006)
                                                  • DAAD Scholarship (2005)


                                                  Fields of interest

                                                  • Atherosclerosis
                                                  • Vascular Injury
                                                  • Inflammatory Mechanisms
                                                  • Macrophage Biology 

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