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Yun Fang

Associate Professor
yunfang@uchicago.edu
Research Summary
My research foci are mechano-transduction mechanisms by which cells sense and convert environmental mechanical stimuli into biological signaling and novel nanomedicine approaches that target dysregulated mechano-sensing pathways. Cellular mechanotransduction is instrumental to embryogenesis and physiological control of tissue homeostasis; abnormal cell responses to mechanical forces promote pathologies associated with numerous human diseases. This is especially important in the vasculature, where environmental mechanical stimuli produce cellular responses in endothelial cells at arterial curvatures and bifurcations by locally disturbed blood flow to induce atherosclerosis. A similar cascade appears to be induced in acute lung injury where it is the increased cyclic stretch that is the trigger. My research program at the University of Chicago focuses on the molecular understanding of endothelial homeostasis governed by mechanical forces, with emphasis upon regulation of non-coding genome, transcription factors, G protein signaling, and genetic variance. Another major research goal is to develop innovative nanomedicine-based therapeutic strategies to treat dysregulated mechano-sensing mechanisms causing vascular diseases. Key Words: microRNA, non-coding RNA, human genetics, enhancer biology, vascular biology, nanotechnology, nanomedicine, mechanotransduction, atherosclerosis, acute lung injury
Education
  • National Taiwan University, Taiwan , BS Microbiology & Plant Pathology 1999
  • University of Pennsylvania, USA, MS Biotechnology 2002
  • University of Pennsylvania, USA, PhD Bioengineering 2006
  • University of Pennsylvania, USA, Postdoctoral Fellow Medicine and Engineering 2012
Biosciences Graduate Program Association
Awards & Honors
  • 2018 - Leif B. Sorensen Faculty Research Award University of Chicago
  • 2019 - Young Investigator Award (First Place) CAAC-ATVB Symposium
  • 2020 - B. Lowell Langille Vascular Biology Lectureship University of Toronto
  • 2022 - NHLBI R35 award National Institutes of Health
Publications

  1. A pleiotropic hypoxia-sensitive EPAS1 enhancer is disrupted by adaptive alleles in Tibetans. Sci Adv. 2022 Nov 25; 8(47):eade1942. View in: PubMed

  2. Intermittent hypoxia inhibits epinephrine-induced transcriptional changes in human aortic endothelial cells. Sci Rep. 2022 10 13; 12(1):17167. View in: PubMed

  3. Targeted polyelectrolyte complex micelles treat vascular complications in?vivo. Proc Natl Acad Sci U S A. 2021 12 14; 118(50). View in: PubMed

  4. Preface. Curr Top Membr. 2021; 87:xiii-xv. View in: PubMed

  5. Mechanical forces and metabolic changes cooperate to drive cellular memory and endothelial phenotypes. Curr Top Membr. 2021; 87:199-253. View in: PubMed

  6. Single-cell lactate production rate as a measure of glycolysis in endothelial cells. STAR Protoc. 2021 09 17; 2(3):100807. View in: PubMed

  7. Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release. Front Physiol. 2021; 12:701995. View in: PubMed

  8. Endothelial Aryl Hydrocarbon Receptor Nuclear Translocator Mediates the Angiogenic Response to Peripheral Ischemia in Mice With Type 2 Diabetes Mellitus. Front Cell Dev Biol. 2021; 9:691801. View in: PubMed

  9. Single-cell metabolic imaging reveals a SLC2A3-dependent glycolytic burst in motile endothelial cells. Nat Metab. 2021 05; 3(5):714-727. View in: PubMed

  10. SARS-CoV-2 Infection Is Associated with Reduced Kr?ppel-like Factor 2 in Human Lung Autopsy. Am J Respir Cell Mol Biol. 2021 08; 65(2):222-226. View in: PubMed

  11. T-Cell Mechanobiology: Force Sensation, Potentiation, and Translation. Front Phys. 2019 Apr; 7. View in: PubMed

  12. Tracking Longitudinal Rotation of Silicon Nanowires for Biointerfaces. Nano Lett. 2020 05 13; 20(5):3852-3857. View in: PubMed

  13. The guidance receptor plexin D1 is a mechanosensor in endothelial cells. Nature. 2020 02; 578(7794):290-295. View in: PubMed

  14. Mechanosensing and Mechanoregulation of Endothelial Cell Functions. Compr Physiol. 2019 03 15; 9(2):873-904. View in: PubMed

  15. Genetic variant at coronary artery disease and ischemic stroke locus 1p32.2 regulates endothelial responses to hemodynamics. Proc Natl Acad Sci U S A. 2018 11 27; 115(48):E11349-E11358. View in: PubMed

  16. Abnormalities of vascular histology and collagen fiber configuration in patients with advanced chronic kidney disease. J Vasc Access. 2019 Jan; 20(1):31-40. View in: PubMed

  17. Endoplasmic Reticulum Protein TXNDC5 Augments Myocardial Fibrosis by Facilitating Extracellular Matrix Protein Folding and Redox-Sensitive Cardiac Fibroblast Activation. Circ Res. 2018 04 13; 122(8):1052-1068. View in: PubMed

  18. Hypercholesterolemia-Induced Loss of Flow-Induced Vasodilation and Lesion Formation in Apolipoprotein E-Deficient Mice Critically Depend on Inwardly Rectifying K+ Channels. J Am Heart Assoc. 2018 03 03; 7(5). View in: PubMed

  19. Protein Mimetic and Anticancer Properties of Monocyte-Targeting Peptide Amphiphile Micelles. ACS Biomater Sci Eng. 2017 Dec 11; 3(12):3273-3282. View in: PubMed

  20. Letter by Wu et al Regarding Article, "Mechanical Activation of Hypoxia-Inducible Factor 1a Drives Endothelial Dysfunction at Atheroprone Sites". Arterioscler Thromb Vasc Biol. 2017 12; 37(12):e197-e198. View in: PubMed

  21. NOTCH1 is a mechanosensor in adult arteries. Nat Commun. 2017 11 20; 8(1):1620. View in: PubMed

  22. Proatherogenic Flow Increases Endothelial Stiffness via Enhanced CD36-Mediated Uptake of Oxidized Low-Density Lipoproteins. Arterioscler Thromb Vasc Biol. 2018 01; 38(1):64-75. View in: PubMed

  23. The Runt of the Litter-Stronger than We Thought? Am J Respir Cell Mol Biol. 2017 08; 57(2):139-140. View in: PubMed

  24. HIF-1a is required for disturbed flow-induced metabolic reprogramming in human and porcine vascular endothelium. Elife. 2017 05 30; 6. View in: PubMed

  25. Experimental Lung Injury Reduces Kr?ppel-like Factor 2 to Increase Endothelial Permeability via Regulation of RAPGEF3-Rac1 Signaling. Am J Respir Crit Care Med. 2017 03 01; 195(5):639-651. View in: PubMed

  26. Oxidized LDL signals through Rho-GTPase to induce endothelial cell stiffening and promote capillary formation. J Lipid Res. 2016 05; 57(5):791-808. View in: PubMed

  27. Mechanosensitive PPAP2B Regulates Endothelial Responses to Atherorelevant Hemodynamic Forces. Circ Res. 2015 Jul 31; 117(4):e41-e53. View in: PubMed

  28. Inhibition of atherosclerosis-promoting microRNAs via targeted polyelectrolyte complex micelles. J Mater Chem B. 2014 Dec 14; 2(46):8142-8153. View in: PubMed

  29. Monocyte-targeting supramolecular micellar assemblies: a molecular diagnostic tool for atherosclerosis. Adv Healthc Mater. 2015 Feb 18; 4(3):367-76. View in: PubMed

  30. The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo. Cardiovasc Res. 2013 Jul 15; 99(2):315-27. View in: PubMed

  31. Site-specific microRNA-92a regulation of Kruppel-like factors 4 and 2 in atherosusceptible endothelium. Arterioscler Thromb Vasc Biol. 2012 Apr; 32(4):979-87. View in: PubMed

  32. MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proc Natl Acad Sci U S A. 2010 Jul 27; 107(30):13450-5. View in: PubMed

  33. Endothelial heterogeneity associated with regional athero-susceptibility and adaptation to disturbed blood flow in vivo. Semin Thromb Hemost. 2010 Apr; 36(3):265-75. View in: PubMed

  34. Cholesterol and ion channels. Subcell Biochem. 2010; 51:509-49. View in: PubMed

  35. Hypercholesterolemia suppresses Kir channels in porcine bone marrow progenitor cells in vivo. Biochem Biophys Res Commun. 2007 Jun 22; 358(1):317-24. View in: PubMed

  36. Evidence for the role of cell stiffness in modulation of volume-regulated anion channels. Acta Physiol (Oxf). 2006 May-Jun; 187(1-2):285-94. View in: PubMed

  37. Hypercholesterolemia suppresses inwardly rectifying K+ channels in aortic endothelium in vitro and in vivo. Circ Res. 2006 Apr 28; 98(8):1064-71. View in: PubMed

  38. Epinephrine overdose-associated hypokalemia and rhabdomyolysis in a newborn. Pharmacotherapy. 2005 Sep; 25(9):1266-70. View in: PubMed

  39. Functional expression of Kir2.x in human aortic endothelial cells: the dominant role of Kir2.2. Am J Physiol Cell Physiol. 2005 Nov; 289(5):C1134-44. View in: PubMed

  40. Cholesterol sensitivity and lipid raft targeting of Kir2.1 channels. Biophys J. 2004 Dec; 87(6):3850-61. View in: PubMed
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