My research instrests include basic and translational research projects, including the studies on the role of extracellular exosomes (EXs) and microvesicles (MVs), stem cell therapy, and renin-angiotensin system in ischemic stroke, hemorrhagic stroke and diabetic ischemic stroke.
M.D. in Clinical Medicine (2005), Medical College of University of South China
Ph.D. in Internal Medicine (2010), Peking University Medical Science Center
Postdoctoral in Pharmacology and Toxicology (2010-2014), Wright State University Boonshoft School of Medicine
- Cell Culture
- Online Journal club
- Integrative Pharmacology and Toxicology Methods
My research interests are mainly in the areas of cerebrovascular diseases and diabetes, specifically in developing novel predictive and therapeutic avenues for ischemic stroke, hemorrhagic stroke and vascular complications of diabetes. My ongoing research topics include:
- Endothelial progenitor cells (EPCs) in vascular protection and tissue repair.
- Extracellular microvesicles (MVs) and exosomes (EXs) in vascular diseases.
- Immunological response in vascular inflammation and injury.
- MVs and EXs in skin injury and wound healing.
EPC priming for functional enhancement with angiotensin converting enzyme (ACE2) and CXCR4 have been studied in my research. The effects of cardiovascular risk factors on the release and cargoes (proteins and microRNAs) of EPC-EXs are currently under investigation. The cross-talk between endothelial cells and neurons, endothelium and keratinocytes mediated by MVs and EXs are also currently being explored.
The approaches applied in my laboratory include molecular, cellular and integrative methodologies. These methods include west blot, real-time PCR, mass spectrum, microRNA sequencing, nanosight tracking analysis (NTA), flow cytometry, etc. Animal surgery methods (MCAO, telemetric probe, osmotic minipump, microinjection) are also used in my research. The animal models used in my research include a spontaneous hemorrhagic stroke model induced in the rennin/angiotensinogen double transgenic (R+A+) hypertensive mice, collagenase-induced focal hemorrhagic stroke model, middle cerebral artery occlusion (MCAO)-induced ischemic stroke, the db/db and STZ-induced diabetic mouse models, and Hasc-/- mouse model. Additionally, I use clinical samples from translational studies of diabetes and stoke patients through collaboration with clinicians.
Reviewer for grant: the Portuguese Foundation for Science and Technology (FCT), Diabetes UK
Reviewer for journals: Scientific Reports, Clinical and Experimental Pharmacology and Physiology, Experimental Physiology, Inflammation Research, Cellular and Molecular Neurobiology, Toxicology Science, Oxidative Medicine and Cellular Longevity, Stem Cell International, Medical Science Monitor, Life Sciences, Methods in Pharmacology and Toxicology
Reviewer for book chapters: Methods in Pharmacology and Toxicology
- Mannis Halurkar, MS, 2017-present, “Effects of EPC-EXs on high glucose and hypoxia/reoxygenation-induced injury of neurons and astrocytes.”
Venkata Sai Usha Sri Polaki, MS, 2018-present, “The role of macrophage polariton in vascular function in hypertensive mice.”
Thesis Advisory Committee
- Ravina M. Ashtaputre, MS 2014-2016, “Proteomic biomarker analysis of amniotic fluid at term and per-term delivery”
- Hala Mustafa Ammar, MS 2012-2014, "The Modulatory Role of Circulating Microvesicles in Endothelial Progenitor Cell Function Is Altered in T2DM"
- Xiang Xiao, MS 2012-2014, “Effects of Ang 1-7 and Endothelial Microvesicles on Ang II-induced Cerebral Endothelial Cell Dysfunction and Apoptosis”
- Ashvin Iyer, MS 2013-2015, “Proteomic and lipidomic profiling of vulvodynia patients”
- Abdelfatah S. Abou Issa, MS 2013-2015, “Effect of oasis ultra-matrix on the healing rate of stage III and IV pressure wounds”
- Langni Liu, MS 2013-2015, “Endothelial Progenitor Cell Derived MVs and Exosomes: Release and Functional Study”
- Mahesh Kodali, MS 2013-2015, “Identification of the collagen types in injured patellar tendons following mesenchymal stem cell therapy in rabbits”
- Sayali Dharmadhikari, MS 2014-2016, "Examining infarct sizes in female sprague dawley rats in response to a delayed post-stroke pharmacological treatment with physical rehabilitation"
- Katherine Fahy, MS 2015-2017, "Thermal burn injury induced microvesicle particle release"
- Qinmao Ye, MS, 2017-2019, "Exosomes released from multiple cells influence the angiogenic function of endothelial cells by regulating miR-29b"
- Azeezat Awoyemi, MS, 2016-2018, “Regulation of microvesicle particle release in keratinocytes."
- Pariksha Thapa, MS, 2017-2019, “kinetics of Microvesicle particles.
- Ma C, Wang J, Liu H, Chen Y, Ma X, Chen S, Chen Y, Bihl J (Co-corresponding author), Yang Y (2018). “Moderate exercise enhances endothelial progenitor cell-exosomes release and function,” Medicine & Science in Sports & Exercise. 2018 Oct.
- Ma X, Wang J, Li J, Ma C, Chen S, Lei W, Yang Y, Liu S, Bihl J (Co-corresponding author), Chen C (2018). “Loading MiR-210 in Endothelial Progenitor Cells Derived Exosomes Boosts Their Beneficial Effects on Hypoxia/Reoxygeneation-Injured Human Endothelial Cells via Protecting Mitochondrial Function,” Cell Physiol Biochem. 2018;46(2):664-675.
- Zhang C, Wang J, Ma X, Wang W, Zhao B, Chen Y, Chen C, Bihl J (2018). “ACE2-EPC-EXs protect ageing ECs against hypoxia/reoxygenation-induced injury through the miR-18a/Nox2/ROS pathway,” J Cell Mol Med. 2018 Jan. 24.
- Liao FL, Tan L, Liu H, Wang JJ, Ma XT, Zhao B, Chen YF, Bihl J, Yang Y, Chen RL (2017). “Hematopoietic stem cell-derived exosomes promote hematopoietic differentiation of mouse embryonic stem cells in vitro via inhibiting the miR126/Notch1 pathway,” Acta Pharmacol Sin. 2017 Oct 19.
- Liu H, Wang J, Chen Y, Chen Y, Ma X, Bihl JC, Yang Y (2017). “NPC-EXs Alleviate Endothelial Oxidative Stress and Dysfunction through the miR-210 Downstream Nox2 and VEGFR2 Pathways,” Oxid Med Cell Longev. 2017:9397631.
- Sun X, Ma X, Wang J, Zhao Y, Wang Y, Bihl JC, Chen Y, Jiang C. Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through miR-21/VEGF signal. Oncotarget. 2017, May 30;8(22):36137-36148.
- Fahy K, Liu L, Rapp CM, Borchers C, Bihl JC, Chen Y, Simman R, Travers JB, "UVB-generated microvesicle particels: A novel pathway by which a skin-speicific stimulus could exert systemic effects," Photochem Photobiol. 2016, Dec 31.
- Pan Q, He C, Liu H, Liao X, Dai B, Chen Y, Yang Y, Zhao B, Bihl J#, Ma X#, “Microvascular endothelial cells-derived microvesicles imply in ischemic stroke by modulating astrocyte and blood brain barrier function and cerebral blood flow,” Mol Brain. 2016, 9(1):63.
- Wang J, Zhong Y, Ma X, Xiao X, Cheng C, Chen Y, Iwuchukwu I, Gaines KJ, Bin Zhao, Liu S, Travers JB, Bihl JC#, Chen Y#, “Analyses of Endothelial Cells and Endothelial Progenitor Cells Released Microvesicles by Using Microbead and Q-dot Based Nanoparticle Tracking Analysis,” Sci Rep. 2016 Apr 20;6:24679. doi: 10.1038/srep24679.
- Wang J, Guo R, Yang Y, Jacobs B, Chen S, Iwuchukwu I, Gaines K, Chen Y, Simman R, Lv G, Wu K, Bihl J, “The Novel Methods for Analysis of Exosomes Released from Endothelial Cells and Endothelial Progenitor Cells,” Stem Cells Int. 2016, 2016: 2639728.
- Wu K, Yang Y, Zhong Y, Zhang P, Guo R, Liu H, Cheng C, Koroscil TM, Chen Y, Liu S, Bihl J, “The effects of microvesicles on endothelial progenitor cells are compromised in type 2 diabetic patients via downregulation of miR-126/VEGFR2 pathway,” Am J Physiol Endocrinol Metab. 2016, Mar 8:ajpendo.00056.2016. doi: 10.1152/ajpendo.00056.2016.
- Bihl J, Rapp C, Chen Y, Travers J, "UVB Generates Microvesicle Particle Release in Part Due to Platelet-activating Factor Signaling," Photochem Photobiol. 2016, 92(3): 503-506.
- Wang J, Chen Y, Yang Y, Xiao X, Chen S, Zhang C, Jacobs B, Zhao B, Bihl J#, Chen Y#, “Endothelial Progenitor Cells and Neural Progenitor Cells Synergistically Protect Cerebral Endothelial Cells from Hypoxia/reoxygenation-induced Injury via Activating the PI3K/Akt Pathway,” Mol Brain, 2016, 9(1):12.
- Bihl J, Zhang C, Zhao Y, Xiao X, Ma X, Chen Y, Chen S, Zhao B, Chen Y, "Angiotensin-(1-7) counteracts the effects of Ang II on vascular smooth muscle cells, vascular remodeling and hemorrhagic stroke: role of the NFkB inflammatory pathway," Vascul Pharmaco, 2015, 73: 115-23.
- Xiao X, Zhang C, Ma X, Miao H, Wang J, Liu L, Chen S, Zeng R, Chen Y, Bihl J, “Angiotensin-(1-7) counteracts angiotensin II-induced dysfunction in cerebral endothelial cells via modulating Nox2/ROS and PI3K/NO pathways”, Exp Cell Res, 2015, 336 (1): 58-65.
- Chen Y, Xiao Y, Lin Z, Xiao X, He C, Bihl J, Zhao B, Ma X, Chen Y, "The role of circulating platelets microparticles and platelet parameters in acute ischemic stroke patients," J Stroke Cerebrovasc Dis, 2015, 24 (10): 2313-20.
- Xiao X, Bi K, Liu Y, Fan R, Zhao Y, Ma X, Wang J, Zhao B, Chen Y, Bihl J, “Cellular membrane microparticles: potential targets of combinational therapy for vascular disease,” Current Vascular Pharmacology, 2015, 4(13): 449-58.
- Zheng J, Li G, Chen S, Bihl J, Buck J, Zhu Y, Xia H, Lazartigues E, Chen Y, Olson JE, "Activation of the ACE2/Ang-(1-7)/Mas pathway reduces oxygen-glucose deprivation-induced tissue swelling, ROS production, and cell death in mouse brain with angiotensin II overproduction," Neuroscience, 2014, 9: 39-51.
- Yi D, Newman M, Bihl J, Chen Y, Simman R, “The preliminary study of effects of tolfenamic acid and cell proliferation, cell apoptosis, and intracellular collagen deposition in keloid fibroblasts in vitro,” Dermatol Res Pract, 2014: 736957
- Chen J, Zhao Y, Chen S, Wang J, Xiao X, Ma X, Penchikala M, Xia H, Lazartigues E, Zhao B, Chen Y, “Neuronal Over-expression of ACE2 protects brain from ischemia-induced damage,” Neuropharmacology, 2014, 79: 550-558.
- Gu S*, Zhang W*, Chen J*, Ma R, Xiao X, Ma X, Yao Z, Chen Y, “EPC-derived microvesicles protect cardiomyocytes from Ang II-induced hypertrophy and apoptosis,” PloS ONE, 2014, 2014, 2;9(1):e85396.
- Ma X, Zhang H, Pan Q, Zhao Y, Chen J, Zhao B, Chen Y, “Citicoline ameliorates hypoxia/aglycemia-induced endothelial dysfunction probably through modulating the expression of tight junction proteins,” PLoS ONE, 2013,8(12): e82604.
- Wang J, Chen S, Ma X, Cheng C, Xiao X, Chen J, Liu S, Zhao B, Chen Y, “Effects of endothelial progenitor cell-derived microvesicles on hypoxia-reoxygenation induced endothelial dysfunction and apoptosis,” Oxid Med Cell Longev, 2013, 2013:572729.
- Chen J, Xiao X, Chen S, Zhang C, Chen J, Yi D, Shenoy V, Raizada MK, Zhao B, Chen Y, “Angiotensin converting enzyme 2 priming enhances the function of endothelial progenitor cells and their therapeutic efficacy,” Hypertension, 2013, 61, pp.681-689.
- Gu X, Lu Y, Chen J, He H, Li P, Yang T, Li L, Liu G, Chen Y, Zhang L, “Mechanisms mediating propofol protection of pulmonary epithelial cells against lipopolysaccharide-induced cell death,” Clin Exp Pharmacol Physiol, 2012, 39(5), pp. 447-53.
- Chen J, Chen J, Chen S, Zhang C, Zhang L, Xiao X, Das A, Zhao Y, Yuan B, Morris M, Zhao B, Chen Y, “Transfusion of CXCR4-primed endothelial progenitor cells reduces cerebral ischemic damage and promotes repair in db/db diabetic mice,” PLoS ONE, 2012, 7(11), e50105.
- Zhao Y, Yuan B, Chen J, Feng D, Zhao B, Qin C, Chen Y, “Endothelial progenitor cells: therapeutic perspective for ischemic stroke,” CNS Neurosci Ther, 2012, 19, pp. 67-75.
- Chen J, Liu Y, Tang Y, Chen J, Hu X, Liu N, Wang S, Zhang Y, Zeng W, Ni H, Zhao B, Chen Y, Tang Z, “Transplantation of adipose-derived stem cells is associated with neural differentiation and functional improvement in a rat model of intracerebral hemorrhage,” CNS Neurosci Ther, 2012, 18(10), pp.847-54.
- Chen J, Chen S, Chen Y, Zhang C, Wang J, Zhang W, Liu G, Zhao B, Chen Y, “Circulating endothelial progenitor cells and cellular membrane microparticles in db/db diabetic mouse: possible implications in cerebral ischemic damage,” Am J Physiol Endocrinol Metab, 2011, 301(1), pp. E62-71.
- Chen J, Wang X, Wu X, Wang Y, Zhao H, Shen B, Wang G, “Intrahepatic levels of PD-1/PD-L correlate with liver inflammation in chronic hepatitis B,” Inflamm Res, 2011, 60(1), pp.47-53.
- Chen J, Wang Y, Wu X, Li J, Hou F, Wang G, “Pegylated interferon α-2b up-regulates specific CD8+ T cells in patients with chronic hepatitis B,” World J Gastroenterol, 2010, 16(48), pp. 6145-50.
- Chen J, Wu X, Wang G, “Hepatoma cells up-regulate expression of programmed cell death-1 in T cells,” World J Gastroenterol, 2008, 14(44), pp. 6853-6857.
1. Bihl J, Wang J, Ma X, Bin Z, Yang Y, Chen Y, (2017) “Exosome and MiRNA in Stroke,” Springer Ser.Translations, Paul A. Lapchak and John H. Zhang (Eds): Cellular and Molecular Approaches to Regeneration and Repair, 978-3-319-66678-5, 433632_1_En, (17)
2010-2011: Member, Society for Neuroscience (SfN)
2011-current: Member, American Heart Association (AHA)
2012-current: Member, National Postdoc Association (NPA)
2012-current: Visiting Assistant Professorship, Guangdong Medical College
2013-current: Membership, WSU Graduate Faculty
2014-current: Committee, National Postdoc Association (NPA)
Ongoing Research Support
1 R01NS102720 Bihl (PI) 05/01/2018-04/30/2023
Exosomes from miR-primed endothelial progenitor cells for treating ischemic stroke
The major goal of this project is to determine the enhanced therapeutic effects of EPC-EXs-miR210on IS by protecting the brain from ischemic injury and promoting neurological recovery. This project will provide the important mechanistic insights into SDF-1α/CXCR4, and relevant miRs, such as miR-126 and miR-210.
16SDG26420078 Bihl (PI) 01/01/2016-12/31/2019
AHA Scientist Development Grant
Role of ACE2 over-expressing endothelial progenitor cells in cerebral hemorrhage
The goal of this project is to determine the preventive and therapeutic role of angiotensin converting enzyme 2 (ACE2) over-expressing endothelial progenitor cells (ACE2-EPCs) in hemorrhagic stroke animal model and determine the underlying mechanisms.
1-17-IBS-187 Bihl (PI) 01/01/2017-12/31/2019
ADA Innovative Basic Science Award
Therapeutic role of miR-126 over-expressing EPC-MVs for ischemic stroke in diabetes
The major goal of this project is to determine the therapeutic role of miR-126-EPC-MVs in ischemic stroke in diabetes by protecting ECs/EPCs/neurons/astrocytes against ischemic and inflammatory injury and promoting angiogenic/neurogenic repair; and determine the predictive role of the levels of cEPC-MVs and their carried miR-126 for ischemic stroke outcomes in diabetic patients.
5 R21 AR071110 Bihl (PI) 07/01/2017-06/30/2019
Microvesicles as a novel transmitter for UVB-induced bioactive products
The major goals of this project are to determine the involvement of PAF-PAFR signaling pathway in mediating UVB-induced MVP release and the effects of antioxidant on UVB-induced MVP release, and determine the bioactive agents in UVB-MVP.
Completed Research Support
13POST14780018 Chen (PI) 01/01/2013-12/31/2014
AHA Post-doctoral Fellowship Award
Role of Angiotensin II/Angiotensin (1-7) balance in intracerebral hemorrhagic stroke
The goal of this project is to investigate the role of Angiotensin II/Angiotensin (1-7) balance in EPC and EC function, and in the progress of intracerebral hemorrhagic stroke and examine the underlying mechanisms related to NFκB.