I have a long-standing interest in cerebrovascular disease research. My current research interest mainly focuses on studying the role of exercise-intervened exosomes in cerebrovascular diseases. We have recently demonstrated that exercise intervention could modulate the release and function of endothelial progenitor cell (EPCs)-derived exosomes. Given exosome function varies upon the parent cell source and status, we postulate that the declined EPC function in hypertension could affect EPC-derived exosome communications with two important brain cells, endothelial cells, and neurons, which will accelerate ischemic injury in the brain. Our initial study suggests that exercise can modulate the EPC-exosome mediated communication of EPCs and neurons. My ongoing study will explore the effects and underlying mechanisms of how exercise modulates the exosomal communications among EPCs and ECs and neurons in hypertension-associated ischemic stroke. In addition, our group recently revealed that exercise intervention could improve endothelial function associated with alleviated inflammation and oxidative stress of perivascular adipose tissue in type 2 diabetic mice. These exciting findings prompt us to further explore the role of exercised-intervened exosomes derived from perivascular adipose tissue on diabetic vascular dysfunction and the underlying mechanism. My long-term goal is to lead a research team to establish a novel extracellular vesicle-based therapy for cerebrovascular diseases such as ischemic stroke and its comorbidities hypertension and diabetes.
Project 1. To study the role of endothelial progenitor cell (EPC) exosomal communication in the beneficial effects of exercise on hypertension-associated ischemic stroke. In this project, we are using the hypertension transgene mouse model to perform exercise. The goal of this study is to investigate the effects and underlying mechanisms of how exercise intervention modulates the exosomal communications among EPCs and two major brain cells, endothelial cells, and neurons, in hypertension-associated ischemic stroke condition.
Project 2. To investigate the functional role of exosomes released from adipose tissue (AT-EXs), especially perivascular adipose tissue, on vascular dysfunction and injury in type 2 diabetes. Vascular disease is one of the major complications of diabetes which affects > 23 million people in the United States. Perivascular adipose tissue (PVAT), long assumed to be only vessel-supporting connective tissue, is now recognized as the sixth “man” of the vascular system. We have recently demonstrated that exercise intervention could improve endothelial function associated with alleviated inflammation and oxidative stress of PVAT in type 2 diabetic mice, but the bioactive mediators for the crosstalk between PVAT and the vasculature are largely unknown. In this project, we aim to determine the role of PVAT-EXs in vascular dysfunction in type 2 diabetes.
In my laboratory, we utilize different animal models, including transgene model (type 2 diabetic mouse, renin-angiotensin transgene mouse, etc.) and disease model (ischemic stroke surgery model, carotid artery wire injury model, etc.), 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, etc. are routinely used in my research.