Karen Stokes, PhD
OTH (1993) - Trinity College - Dublin, Ireland
PhD (2004) - Trinity College - Dublin, Ireland
The Stokes lab has four key areas of interest, all related to cerebrovascular disease and the microvasculature:
- Recent epidemiological studies have revealed that infectious agents, for example cytomegalovirus (CMV), may contribute to cardiovascular disease. CMV is a beta-herpes virus that has been identified in atherosclerotic lesions, and accelerates disease progression in hyperlipidemic animals. This virus induces an inflammatory and thrombogenic phenotype in isolated cells, and we have evidence that CMV also induces endothelial dysfunction in arterioles in vivo. Furthermore, we have shown CMV exacerbates hypercholesterolemia- and mild obesity-induced leukocyte and platelet recruitment in postcapillary venules, and synergizes with hypercholesterolemia to worsen thrombosis. Therefore, our focus is to investigate the underlying mechanisms involved in the detrimental microvascular responses to CMV, as well to understand how CMV synergizes with other cardiovascular risk factors in the generation of a pro-inflammatory phenotype. In particular, we are interested in how platelets, through interaction/communication with neutrophils, monocytes and endothelial cells, participate in CMV-induced microvascular alterations in the brain.
- Diabetes is a significant risk factor in the clinical outcome of cerebrovascular disease, such as stroke. Elevated blood glucose and reactive carbonyl species (RCS) such as methylglyoxal (MG) are characteristic features of diabetes. RCS are potent cross-linking agents that can target and modify the brain microvascular endothelium, and cause vascular inflammation and thrombosis. In addition, RCS can directly glycate proteins of leukocytes and platelets, which could contribute to inflammatory and thrombotic responses. We are investigating the role of MG in both the enhanced risk for stroke and the worse outcome following stroke in diabetes. By manipulating components of the MG elimination pathway, we will determine if targeting one or more steps could provide protection against stroke in diabetics. We are currently funded for a pilot grant to translate this concept to diabetic stroke patients.
- The third project also focuses on the impact of diabetes on the brain microvasculature. Here we are assessing the role for redox pathways in the exacerbation of Alzheimer’s Disease by diabetes. Currently we are characterizing the changes in reactive species in the brain and plasma in Alzheimer’s Disease mice on normal and high fat diet, with our ultimate goal of manipulating sulfides to improve cognitive and vascular outcomes.
- The most recent project is centered around the fact that sickle cell disease causes inflammation, and inflammatory cells such as neutrophils may in turn promote the thrombotic complications of sickle cells disease, for example stroke. Thus, ware investigating the role of neutrophil-derived reactive oxygen species in cerebral thrombosis in sickle cell mice.
- Wang B, Yee Aw T, Stokes KY. N-acetylcysteine attenuates systemic platelet activation and cerebral vessel thrombosis in diabetes. Redox Biol. 2018 Apr;14:218-228. PubMed PMID: 28961512; PubMed Central PMCID: PMC5619994.
- Wang B, Aw TY, Stokes KY. The protection conferred against ischemia-reperfusion injury in the diabetic brain by N-acetylcysteine is associated with decreased dicarbonyl stress. Free Radic Biol Med. 2016 Jul;96:89-98. PubMed PMID: 27083477; PubMed Central PMCID: PMC5079522.
- Brunson JL, Becker F, Stokes KY. The impact of primary and persistent cytomegalovirus infection on the progression of acute colitis in a murine model. Pathophysiology. 2015 Mar;22(1):31-7. Doi: 10.1016/j.pathophys.2014.11.001. Epub 2014 Nov 18. PubMed PMID: 25511533; PubMed Central PMCID: PMC4329059.
- Khoretonenko MV, Brunson JL, Senchenkov E, Leskov IL, Marks CR, Stokes KY. Platelets, acting in part via P-selectin, mediate cytomegalovirus-induced microvascular dysfunction. Am J Physiol Heart Circ Physiol. 2014 Dec 15;307(12):H1745-53. Doi: 10.1152/ajpheart.00201.2014. Epub 2014 Oct 17. PubMed PMID: 25326535; PubMed Central PMCID: PMC4269701.
Complete List of my Published Work in MyBibliography: LEARN MORE
Currently: We are excited to be funded for several projects and are actively seeking postdoctoral fellows to help build up our team again to investigate cerebrovascular diseases – we’d love for you to join our team. Click on the “Positions” tab for further information. We also periodically look for some talented undergraduate students who are interested in cerebrovascular disease – so please keep checking!
August 2019: A HUGE CONGRATULATIONS to Israel Soto, who has left the lab and started his new job. We wish him all the very best.
June 2019: Dr. Stokes was awarded an NIH R25 grant to establish a summer research program. The inaugural year of the Cardiovascular Undergraduate Research Initiative for Underrepresented Students (CURIOUS) program took place over the summer and was a great success. Thank you all who participated! An extra thank you to Kaylynn Gruber who joined our lab and ran many western blots!
We look forward as we prepare to open up the program applications for 2020 – updates will be posted in November.
We are not currently recruiting Post-Doctoral Fellows at this time.
Graduate students interested in conducting research in the Stokes lab should review the current laboratory research directions and contact Dr. Stokes at email@example.com.
Undergraduate Research Assistants
We are not currently hiring any additional undergraduates. However, positions can become available during the summer.
Medical Students, Residents, and Fellows
The Stokes laboratory has a number of research projects available for any Medical Students, Residents, and Fellows. Those who are interested should contact Dr. Stokes directly at firstname.lastname@example.org.