Audrey Cleuren, Ph.D.
Cardiovascular Biology Research Program
Endothelial cells form the inner lining of blood vessels, where they create a barrier between the blood and the underlying tissue. Besides having basic functions such as controlling blood flow and transporting oxygen and nutrients into tissues, they also have very unique properties depending on their location in the body. For example, endothelial cells in the brain need to be tightly connected to each other to prevent the passage of potentially damaging substances to the central nervous system, while in the kidney they act more like a sieve to allow filtering of large volumes of blood to remove waste products. Although we have known for a long time that endothelial cells have unique functions in different organs, one important question remained unanswered: How is this endothelial specialization achieved?
By using mouse models we have been able to start unraveling the genetic driving forces behind the functional diversity of endothelial cells across organs. Knowing how healthy endothelial cells function is of great importance, as many diseases are associated with a disruption of this normal tissue-specific endothelial cell function. My research focuses on studying mechanisms contributing to endothelial (dys)function in disease initiation and progression, with the goal to identify targets that can be used for therapeutic interventions.
Endothelial cells (ECs) form a critical barrier between circulating blood and parenchymal cells and play a central role in the physiologic regulation of nutrient transport, vascular tone, cell adhesion and blood fluidity. However, the endothelium also plays an important role in pathological conditions, either as a passive bystander, or more frequently as an active contributor to pathogenesis. Despite this known contribution, in vivo studies addressing gene expression programs underlying different EC phenotypes have been relatively limited, as ECs are highly heterogeneous and poorly accessible given their low numbers and interspersed distribution within tissues. By combining transgenic mouse models and high-throughput sequencing methods we have been able to accurately profile endothelial cells directly from their native in vivo environment, showing a high degree of endothelial heterogeneity across organs.
We are now expanding these studies by investigating the molecular mechanisms underlying EC (dys)function in pathologic conditions, with a particular focus on unraveling the contribution of the endothelium in the host response to infection. ECs play a key role in orchestrating this host reaction by activating inflammation and coagulation pathways to contain the pathogen and prevent its dissemination via the vascular compartment. However, an uncontrolled or maladaptive response can lead to EC dysfunction. This is characterized by increased vascular permeability, reduced endothelial reactivity and a dysregulation in the hemostatic and inflammatory properties of the endothelium, which can eventually result in coagulopathies as seen in sepsis or hemorrhagic fevers. We have previously modeled bacterial sepsis by injecting mice with lipopolysaccharide (LPS), showing that there is vascular bed-specific variation in endothelial reactivity in response to LPS exposure. Similar studies using viral pathogens are ongoing and aim to identify commonly shared mechanisms and key regulators affecting EC function in bacterial and viral infections, with the ultimate goal to establish disease-specific targets that can be used for therapeutic interventions.
B.S., University of Leiden, Leiden, the Netherlands, 2005
M.S., University of Leiden, Leiden, the Netherlands, 2007
Ph.D., Einthoven Laboratory for Experimental Vascular Medicine, Leiden, the Netherlands, 2011
Honors and Awards
Outstanding Poster Award, North American Vascular Biology Organization, 2017
Young Investigator Award, International Society on Thrombosis and Haemostasis, 2011, 2015
Science Prize, Dutch Society on Thrombosis and Hemostasis, 2011
Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB), ad hoc manuscript reviewer
Journal of Thrombosis and Haemostasis, ad hoc manuscript reviewer
eLife, ad hoc manuscript reviewer
International Society on Thrombosis and Haemostasis, 2009-present
American Heart Association, 2015-present
North American Vascular Biology Organization, 2016-present
American Society of Hematology, 2017-present
Joined OMRF’s scientific staff in 2021
Van der Ent MA, Svilar D, Cleuren ACA. Molecular analysis of vascular gene expression. Res Pract Thromb Haemost 6:e12718, 2022 May, PMID: 35599705, PMCID: PMC9118339
Cleuren AC, Van der Ent MA, Jiang H, Hunker KL, Yee A, Siemieniak DR, Molema G, Aird WC, Ganesh SK, Ginsburg D. The in vivo endothelial cell translatome is highly heterogeneous across vascular beds. Proc Natl Acad Sci USA 2019;116(47):23618-23624. PMID: 31712416, PMCID: PMC6876253.
Zhang N, Czepielewski RS, Jarjour NN, Erlich EC, Esaulova E, Saunders BT, Grover SP, Cleuren AC, Broze GJ, Edelson BT, Mackman N, Zinselmeyer BH, Randolph GJ. Expression of factor V by resident macrophages boosts host defense in the peritoneal cavity. J. Exp. Med. 2019; 216(6):1291-1300. PMID: 31048328, PMCID: PMC6547866.
Westrick RJ, Tomberg K, Siebert AE, Zhu G, Winn ME, Dobies SL, Manning SL, Brake MA, Cleuren AC, Hobbs LM, Mishack LM, Johnston AJ, Kotnik E, Siemieniak DR, Xu J, Li JZ, Saunders TL, Ginsburg D. Sensitized mutagenesis screen in Factor V Leiden mice identifies thrombosis suppressor loci. Proc Natl Acad Sci USA. 2017;114(36):9659-9664. PMID: 28827327, PMCID: PMC5594664.
Everett LA, Cleuren AC, Khoriaty RN, Ginsburg D. Murine coagulation factor VIII is synthesized in endothelial cells. Blood. 2014;123(24):3697-705. PMID: 24719406, PMCID: PMC4055920.
Cleuren AC, van der Linden IK, De Visser YP, Wagenaar GT, Reitsma PH, van Vlijmen BJ. 17α-Ethinylestradiol rapidly alters transcript levels of murine coagulation genes via estrogen receptor α. J Thromb Haemost. 2010;8(8):1838-46. PMID: 20524981
Cardiovascular Biology Research Program, Mail Stop 45
825 NE 13th Street
Oklahoma City, Oklahoma 73104
Phone: (405) 271-4785
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Mariko Kudo, Ph.D.
Lauren Miller, Ph.D.
Research Technician IV
Administrative Assistant II