Dr. Fang’s research group has broad interests and deep expertise in vascular biology, non-coding genome, and nano-medicine. We have contributed significantly to new molecular mechanisms leading to arterial (atherosclerosis) and pulmonary (acute lung injury) vascular diseases and strive to engineer new multifunctional, multivalent nanomaterials to spatially deliver therapeutic nucleotides that modify these disease-causing cellular events. Our studies investigated molecular understandings of endothelial homeostasis governed by mechanical stimuli (blood flow and cyclic stretch), with emphasis upon regulation of non-coding RNAs, transcription factors, ion channels, G protein signaling, and genetic variance. The work in the laboratory combines multi-disciplinary approaches including high-throughput sequencing, bioinformatics, human genetics, bioengineering systems, materials science, cell/molecular biology techniques as well as experimental in vivo and in vitro models. We have applied abovementioned technologies elucidating novel endothelial mechano-transduction mechanisms related to genome-wide association studies (GWAS) of coronary artery disease (CAD) and acute lung injury (ALI). Our recent results demonstrate that disturbed flow significantly reduces endothelial PhosPhatidic-Acid-Phosphatase-type-2B (PPAP2B/LPP3/PLPP3, a GWAS CAD gene) through miR-92a up-regulation and KLF2 suppression. In addition, mechano-sensitive transcription factor KLF2, notably reduced in inflamed lungs, forms a highly interconnected network with GWAS-implicated ALI genes. We have engineered innovative polymeric nano-carriers (polyelectrolyte complex micelles) that preferentially target inflamed endothelium to deliver therapeutic nucleotides, aiming to treat these dys-regulated mechano-sensing mechanisms in atherosclerosis and acute lung injury.

  1. Huang RT, Wu D, Meliton A, Oh MJ, Krause M, Lloyd JA, Nigdelioglu R, Hamanaka RB, Jain MK, Birukova A, Kress JP, Birukov KG, Mutlu GM, Fang Y. Experimental lung injury reduces KLF2 to increase endothelial permeability via regulation of RAPGEF3-Rac1 signaling. Am J Respir Crit Care Med, 2017. In Press.
  2. Wu C, Huang RT, Kuo KC, Kumar S, Kim CW, Lin YC, Chen YJ, Birukova A, Birukov KG, Dulin NO, Civelek M, Lusis AJ, Loyer X, Tedgui A, Dai G, Jo H, Fang Y. Mechano-sensitive PPAP2B regulates endothelial responses to athero-relevant hemodynamic forces. Circ Res. 17(4):e41-53, 2015.
  3. Kuo KC, Leon L, Chung EJ, Huang RT, Sontag TJ, Reardon CA, Getz GS, Tirrell M, Fang Y. Inhibition of atherosclerosis-promoting microRNAs via targeted polyelectrolyte complex micelles. J Mater Chem B Mater Biol Med. 2:8142-8153, 2014.
  4. Fang Y, Davies PF. Site-specific microRNA-92a regulation of Kr├╝ppel-Like Factors 4 and 2 in atherosusceptible endothelium. Arterioscler Thromb Vasc Biol. 32:979-987, 2012.
  5. Fang Y, Shi C, Manduchi E, Civelek M, Davies PF. MicroRNA-10a regulation of pro-inflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proc Natl Acad Sci U S A. 107:13450-5, 2010.

We strive to contribute to and exploit a deeper understanding of mechanobiology in vascular cells related to human diseases and furthermore, develop innovative nanomedicine-based therapeutic strategy to treat vascular diseases.

Dr. Fang’s laboratory has broad interests and deep expertise in vascular biology, non-coding genome, and nano-medicine. We investigate the pathophysiological mechanisms of vascular diseases, particularly the modulation of vascular health by non-coding genome in the context of cardiovascular complication (atherosclerosis) and pulmonary disease (acute lung injury). Our major research goals are 1) to elucidate novel non-coding genome-mediated disease mechanisms and 2) to develop new nanomedicine-based diagnostic and therapeutic applications. The Fang lab applies multi-disciplinary approaches including high-throughput sequencing, bioinformatics, material sciences, human genetics, bioengineering tools, and cell/molecular biology techniques as well as experimental in vivo and in vitro models

 
 

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    Institute for Integrative Physiology

    The University Of Chicago
    Geri Harges
    Administrative Specialist
    5841 South Maryland Avenue
    Chicago, Illinois 60637
    773-834-5254
    Email: gharges1@medicine.bsd.uchicago.edu