Lei Yuan, M.D., Ph.D.
Instructor of Medicine
Beth Israel Deaconess Medical Center
Harvard Medical School
330 Brookline Avenue, RN-247
Boston, MA 02215
Lei Yuan received her medical training in China. She earned a Ph.D. in Biology from Boston College in 2005. She then joined BIDMC for her post-doctoral training and obtained a faculty position at Center for Vascular Biology Research of BIDMC in July 2012.
Research Interests: Vascular Niche/Cardiomyocyte Function & Metabolism
Basic Research: Our research focuses on deciphering the angiocrine function of vascular niche in cardiomyocytes particularly in cardiac hypertrophy and heart failure. Using genetic engineering approaches in mouse model in vivo and in tissue culture in vitro, we are interested in understanding the angiogenic and metabolic regulation of cardiomyocytes by the endothelium. We believe that the endothelium is a dynamically active organ. The placental growth factor (PlGF), an angiocrine factor produced by endothelial cells, contributes to the organ-specific phenotype and function of cardiomyocytes. We are currently exploring the novel mechanisms underlying PIGF- mediated vascular niche and cardiomyocyte metabolism in the heart and the role of mechanosensory pathways in angiocrine modulation.
New and Noteworthy Publications:
Yuan L, Chan G, Beeler D, Janes L, Spokes KC, Mojiri A, Adams WJ, Sciuto T, Garcia-Cardeña G, Molema G, Jahroudi N, Marsden PA, Dvorak A, Regan ER, Aird WC. Organ-specific stochastic phenotype switching is required for endothelial health (submitted). 2014. This study demonstrates the organ-specific endothelial mosaic heterogeneity as a result of bistable switch driven by biological noise, giving insight into the molecular mechanism of underlying epigenetic control.
Yuan L, Janes L, Beeler D, Spokes KC, Smith J, Li D, Jaminet SC, Oettgen P, Aird WC. Role of RNA splicing in mediating lineage-specific expression of the von Willebrand factor gene in the endothelium. Blood. 2013;121:4404-12. In this paper we employ the knockin/knockout technique in mouse system to define the role of intron in regulating gene expression in EC in vivo.
Yuan L, Le Bras A, Sacharidou A, Itagaki K, Zhan Y, Kondo M, Carman CV, Davis GE, Aird WC, Oettgen P. ERG controls endothelial cell permeability via transcriptional regulation of claudin-5 (CLDN5). J Biol Chem. 2012;287:6582-91. This paper reveals the novel role of ERG in mediating EC permeability.
Yuan L, Sacharidou A, Stratman AN, Le Bras A, Zwiers PJ, Spokes K, Bhasin M, Shih SC, Nagy JA, Molema G, Aird WC, Davis GE, Oettgen P. RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG. Blood. 2011;118:1145-53. This paper characterizes the EC-enriched GTPase RhoJ as a novel target of ERG and their involvement in EC morphogenesis.
Yuan L, Nikolova-Krstevski V, Zhan Y, Kondo M, Bhasin M, Varghese L, Yano K, Carman CV, Aird WC, Oettgen P. Antiinflammatory effects of the ETS factor ERG in endothelial cells are mediated through transcriptional repression of the interleukin-8 gene. Circ Res. 2009;104:1049-57. This paper for the first time indicates the role of ERG in regulating EC inflammation and dysfunction.