Jinju Wang, PhD
Assistant Professor
435N BBSC
wangjin@marshall.edu

Research Statement

My research interests primarily focus on the physiological and pathological roles of extracellular vesicles (EVs) and their potential as therapeutic agents in cerebrovascular diseases, including ischemic stroke and vascular dementia. Stroke is the fifth leading cause of death in the United States. Ischemic stroke accounts for over 85% of all strokes. Current treatments are limited due to narrow therapeutic windows of 4.5 hrs from the onset of symptoms. Vascular dementia is the second most common type of dementia, accounting for 15-20% of dementia cases in North America and Europe. Despite the high prevalence, treatment options also remain limited. Vascular dementia, particularly vascular cognitive impairment and dementia (VCID), is characterized by endothelial dysfunction, white matter injury, and progressive cognitive deficits. Currently, there are no effective therapies that target the cerebrovascular and white matter damage underlying VCID. The molecular mechanisms behind the onset and progression of cognitive impairment remain unclear. My work aims to uncover how EVs contribute to neurovascular health and disease, particularly under conditions such as hypertension, diabetes, and aging, which are key risk factors for both stroke and dementia. We have demonstrated that exosomes derived from endothelial progenitor cells (EPC-EXs) exert protective effects in the ischemic brain. Furthermore, interventions such as exercise or targeting specific microRNAs and proteins may enhance the beneficial properties of these exosomes, even in hypertensive models of stroke. More recently, we have shown that exosome-mediated communication between EPCs and brain cells (neurons and brain microvascular endothelial cells) is impaired under hypertensive conditions, potentially contributing to early cerebrovascular dysfunction and the progression of vascular dementia. These findings have sparked new investigations into how hypertension alters EV signaling and function. We aim to advance understanding of EV biology in the context of cerebrovascular disease and ultimately develop novel EV-based strategies to protect brain health, decelerate cognitive decline, and promote healthy aging.

Biosketch

Wang Biosketch

Current Projects

Project 1. To study the therapeutic potential of EPC-EXs on ischemic stroke. The incidence of ischemic stroke (IS) rises significantly with aging and in the hypertension population [1]. Exosomes (EXs) are emerging as novel vehicles for therapeutic purposes that can convey cargo such as microRNAs (miRs) and proteins. Endothelial progenitor cell (EPC)-derived EXs (EPC-EXs) can protect the brain against ischemia injury through miR delivery. Our recent study reveals that the communication capability of EPC-EXs from hypertensive transgenic mice with brain ECs is compromised, suggesting that EPC-EXs might be a therapeutic target for hypertension-related IS. Angiotensin-converting enzyme 2 (ACE2), a negative regulator of the renin-angiotensin system, has recently been suggested to be a new player in aging- and hypertension-related cerebrovascular diseases. The deficiency of ACE2 augments endothelial dysfunction with aging, whereas ACE2 over-expression alleviates ischemic injury in hypertensive mice. The goal of this study is to examine the therapeutic effects of EXs derived from angiotensin converting enzyme 2 (ACE2)-overexpressing EPCs in hypertension-related ischemic stroke.

Project 2. To investigate the roles of extracellular vesicles in vascular health and cognitive impairment throughout the lifespan. Vascular dementia is the second most common dementia-related disease worldwide. However, there is no effective treatment besides managing risk factors like hypertension and diabetes. The molecular mechanisms behind the onset and progression of cognitive dysfunction remain unclear. Emerging evidence highlights the importance of circulating extracellular vesicles (cEVs) in intercellular communication and vascular regulation. Nonetheless, how cEV cargo changes with age and their functional effects on vascular cognitive decline are not well understood. In this project, we aim to explore the roles of cEVs in hypertension-related cognitive impairment across the lifespan.

In my laboratory, we utilize different animal models, including transgenic models (type 2 diabetic mouse, renin-angiotensin transgene mouse) and disease models (ischemic stroke surgery model, bilateral carotid artery stenosis), molecular and cellular biology approaches to test our hypotheses. Techniques including small animal microscopic surgeries (telemetric probe implantation, adipocyte tissue transplantation, tail vein injection, stereotactic microinjection), exercise training, behavior tests, Nanoparticle tracking analysis (NTA), cell culture, qRT-PCR, flow cytometry, and confocal microscopy are routinely used in my research.

Laboratory Personnel

Gideon Udoh, B.S, Research Technician (volunteer)
Shuzhen Chen, MD., Research Associate
Smara Sigdel, Undergraduate Student

Publications

Wang Publications

PubMed Publications

Wang, Jinju

Research Statement