Yang Lab

Research Interests

Principal Investigator Yi Yang, MD, PhD leads the research of the Yi Yang Lab which is focused on the understanding and translational potential of the cellular and molecular mechanisms of brain injury and the neurovascular remodeling associated with ischemic cerebral stroke and vascular contributions to cognitive impairment and dementia (VCID).

The long-term goal is to facilitate the development of more precisely targeted therapeutic approaches to reduce the progressive brain injury and to improve recovery following neurological disorders.

Defining the role of MMPs

Our earlier work has been seminal in defining the role of the matrix metalloproteinase (MMPs) in the disruption of the tight junction proteins (TJPs) in the blood-brain barrier (BBB) after stroke.

Studies on alternate roles of MMPs in the cell nucleus on DNA repair and neuronal apoptotic death has been pioneering in the field. Previous findings also indicated the critical role of MMPs, particularly MMP-2 and -3, in stroke-induced angiogenesis during brain repair.

Recent Findings

Recently, the Yi Yang Lab has demonstrated that spontaneous angiogenesis vessels in the peri-infarct area have high BBB permeability due to the lack of two major endothelial TJPs. These findings emphasize the current challenges to promote angiogenesis in the ischemic brain as a therapeutic strategy: facilitation of functional BBB restoration and determination of appropriate points of intervention for functional vascular remodeling.

Further studies based on animal model and cell cultures have demonstrated that cross-talk between cells in neurovascular units, such as pericytes, astrocytes, and microglia, plays a critical role in BBB restoration in newly formed vessels in the peri-infarct area during stroke recovery.

Fully Funded Projects

The primary focus of Dr. Yang’s NIH- and AHA-funded projects is to characterize the cellular and molecular mechanisms through which functional BBB is formed in response to spontaneous and therapy-induced vascular remodeling in ischemic brain, as well as to monitor dynamics of functional neurovascular remodeling during recovery from stroke utilizing interdisciplinary methods.

Additional interests are to elucidate the role of NG2-pericyte pathway in regulating TJPs formation of BBB during stroke-induced vascular remodeling. We are also working on delineating the vascular mechanisms that trigger the progressive VCID pathological cascades in animal models and the molecular and cellular targets that can support the BBB functions to ameliorate the progressive cerebral lesions in VCID.

Some of the experimental models and approaches we routinely use include rodent models of cerebral ischemia and VCID, neuronal and 3D BBB cultures, mouse genetic models, MRI, specific antibody-conjugated nanoparticles, biochemical and molecular studies, histological and behavioral evaluations.