The Yao Lab is interested in basement membrane (BM) biology with a focus on the CNS and skeletal muscle. Specifically, the Yao Lab has been studying: (1) how the BM regulates the Blood Brain Barrier (BBB) integrity in both physiological and pathological conditions; (2) how the BM regulates the stemness (proliferation, differentiation, and fate determination) of pericytes and muscle development & regeneration after injury. The goals of the Yao Lab are to fully understand the biological functions of the BM and develop novel therapies for various neurological disorders & muscular dystrophy.Currently, Dr. Yao’s lab is working on two major projects: the Brain Project and the Muscle Project.
Brain Project
The BBB is a dynamic structure that maintains the homeostasis of the CNS. BBB breakdown has been found to be not only the result but also a cause of various neurological disorders. The BBB is mainly composed of brain microvascular endothelial cells, pericytes, astrocytes, and a non-cellular component—the BM. The BM is a highly organized special extracellular matrix containing laminin, collagen, nidogen, and heparan sulfate proteoglycans. Among these components, laminin is the only one that is absolutely required for BM formation. Interestingly, various laminin isoforms exist and different cells synthesize distinct laminin isoforms. The Yao Lab is investigating how individual laminin isoforms regulate BBB maturation and BBB integrity under physiological conditions using various (endothelium-, pericyte-, and astrocyte-specific) conditional laminin knockout mouse-lines. Previous studies from the Yao Lab showed that loss of astrocyte-derived laminins leads to BBB disruption and intracerebral hemorrhage, whereas loss of pericyte-derived laminins results in a milder CNS phenotype (BBB breakdown and hydrocephalus) in age- and genetic background-dependent manners. Ongoing research focuses on endothelial laminins. In addition, utilizing these transgenic mice, the Yao Lab is also investigating the roles of different laminin isoforms in various neurological disorders, including stroke (both hemorrhagic and ischemic).
Muscle Project
Pericytes are perivascular stem/progenitor cells with multipotent activity. On one hand, they can undergo myogenesis contributing to muscle regeneration. On the other hand, pericytes are able to differentiate into adipocytes leading to muscle degeneration. How pericyte differentiation and fate determination are regulated, however, remains elusive. The Yao Lab reported that laminin is a key regulator in these processes. Specifically, pericyte-derived laminins are required for the myogenesis of pericytes, but inhibit the adipogenesis of pericytes. Furthermore, the Yao Lab showed that exogenous laminin-111 is able to improve muscle pathology at structural, biochemical, and functional levels in a congenital muscular dystrophy model. The clinical application of laminin treatment, however, is prevented by its large molecular size and/or limited diffusion after injection. Following studies will focus on: (1) determining the molecular mechanisms underlying laminin’s effect in pericyte differentiation & fate determination; and (2) developing novel & effective therapies for various muscle disorders, including muscular dystrophy.
