Postdoctoral Fellow, Neurobiology and Genetics, The Rockefeller University, New York, NY
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.
- Xi Kuang, Yao Yao, Jun-Rong Du, Yan-Xin Liu, Cheng-Yuan Wang, Zhong-Ming Qian. Neuroprotective role of Z-ligustilide against forebrain ischemic injury in ICR mice. Brain Research 2006, 1102(1): 145-153.
- Jun-Rong Du,Yan Yu, Yao Yao, Bo Bai, Xu Zong, Cheng-Yuan Wang, Zhong-Ming Qian. Ligustilide reduces phenylephrine induced-aortic tension in vitro but has no effect on systolic pressure in spontaneously hypertensive rats. The American Journal of Chinese Medicine 2007, 35(3): 487-496.
- Yao Yao, Stella E Tsirka. The C-terminus of mouse monocyte chemoattractant protein 1 (MCP1) mediates MCP1 dimerization while blocking its chemotactic potency. Journal of Biological Chemistry 2010, 285(41): 31509-31516.
- Yao Yao, Stella E Tsirka. Truncation of monocyte chemoattractant protein 1 by plasmin promotes blood-brain barrier disruption. Journal of Cell Science 2011, 124 (Pt 9): 1486-1495.
- Yao Yao, Stella E Tsirka. Mouse MCP1 C-terminus inhibits human MCP1-induced chemotaxis and BBB compromise. Journal of Neurochemistry 2011, 118 (2): 215-223.
- Yao Yao, Stella E Tsirka. The CCL2-CCR2 system affects the progression and clearance of intracerebral hemorrhage. Glia 2012, 60 (6): 908-918.
- Yao Yao, Stella E Tsirka. Chemokines and Their Receptors in Intracerebral Hemorrhage. Translational Stroke Research 2012, 3 (suppl. 1): 70-79.
- Zu-Lin Chen, Yao Yao, Erin H. Norris, Anna Kruyer, Odella Jno-Charles, Akbarshakh Akhmerov, and Sidney Strickland. Ablation of astrocytic laminin leads to hemorrhagic stroke and impairs vascular smooth muscle cell differentiation. Journal of Cell Biology 2013, 202(2): 381-395.
- Yao Yao, Zu-Lin Chen, Erin H. Norris, and Sidney Strickland. Astrocytic laminin regulates blood-brain barrier integrity and pericyte differentiation. Nature Communications 2014, 5: 3413.
- Yao Yao*, Stella E Tsirka. Monocyte Chemoattractant Protein-1 and Blood-Brain Barrier. Cellular and Molecular Life Sciences 2014, 71(4): 683-697.
- Yarong He#, Yao Yao#, Stella E. Tsirka, Yu Cao. Cell-Culture Models of the Blood-Brain Barrier. Stroke 2014, 45(8): 2514-2526. (#These authors contributed equally to this work)
- Yao Yao*, Stella E Tsirka. Mouse Monocyte Chemoattractant Protein 1 (MCP1) Functions as a Monomer. The International Journal of Biochemistry & Cell Biology 2014, 55C: 51-59.
- Yao Yao, Erin H. Norris, Sidney Strickland, The cellular origin of laminin determines its role in blood pressure regulation. Cellular and Molecular Life Sciences 2015, 72: 999-1008.
- Yao Yao*, Erin H. Norris, Christopher Mason, and Sidney Strickland*. Laminin regulates PDGFRβ+ cell stemness and muscle development. Nature Communications 2016, 7: 11415.
- Commented on Rockefeller’s Newswire: http://newswire.rockefeller.edu/2016/06/01/new-insights-into-muscular-dystrophy-point-to-potential-treatment-avenues/
- Highlighted on DM Research News by Myotonic Dystrophy Foundation: http://us8.campaign-archive1.com/?u=8f5969cac3271759ce78c8354&id=7a86a9e46b&e=df17d4f3f5
- Young Cheul Chung, Anna Kruyer, Yao Yao, Emily Feierman, Allison Richards, Sidney Strickland, Erin H. Norris. Hyperhomocysteinemia exacerbates Alzheimer’s disease pathology by way of the Aβ-fibrinogen interaction. Journal of Thrombosis and Haemostasis 2016, 14: 1-11.
- Jyoti Gautam, Xuanming Zhang, and Yao Yao*. The role of pericytic laminin in blood brain barrier integrity maintenance. Scientific Reports 2016, 6: 36450.
- Yao Yao*. Laminin: loss of function studies. Cellular and Molecular Life Sciences 2017, 74: 1095-1115.
- Jyoti Gautam, Abhijit Nirwane, and Yao Yao*. Laminin differentially regulates the stemness of type I and type II pericytes. Stem Cell Research & Therapy 2017, 8: 28.
- Abhijit Nirwane, Jyoti Gautam, and Yao Yao*. Isolation of type I and type II pericytes from mouse skeletal muscles. Journal of Visualized Experiments (JoVE) 2017, In press.
2017 ISC 2017 Stroke Basic Science Award, American Heart Association
2016 Scientist Development Grant, American Heart Association
2016 Travel Scholarship, 2016 Annual Blood-Brain Barrier Consortium Meeting
2015 Poster Award, Gordon Research Conference: Vascular Cell Biology
2015 Teacher of the Semester, Class of 2018, College of Pharmacy UMN
2014 Fund-A-Fellow Grant, Myotonic Dystrophy Foundation
2013 Certificate of Excellence in Reviewing, Neurobiology of Disease
2012 BD Bioscience Stem Cell Research Grant, BD
2012 Merck Postdoctoral Fellowship, Merck & The Rockefeller University
2010 BioLegend Young Investigator Travel Award, BioLegend