Yun Fang

Associate Professor
Websites
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
Publications
  1. Zhou Z, Yeh CF, Mellas M, Oh MJ, Zhu J, Li J, Huang RT, Harrison DL, Shentu TP, Wu D, Lueckheide M, Carver L, Chung EJ, Leon L, Yang KC, Tirrell MV, Fang Y. Targeted polyelectrolyte complex micelles treat vascular complications in vivo. Proc Natl Acad Sci U S A. 2021 12 14; 118(50). View in: PubMed

  2. Fang Y. Preface. Curr Top Membr. 2021; 87:xiii-xv. View in: PubMed

  3. Li J, Fang Y, Wu D. Mechanical forces and metabolic changes cooperate to drive cellular memory and endothelial phenotypes. Curr Top Membr. 2021; 87:199-253. View in: PubMed

  4. Harrison D, Wu D, Huang J, Fang Y. Single-cell lactate production rate as a measure of glycolysis in endothelial cells. STAR Protoc. 2021 09 17; 2(3):100807. View in: PubMed

  5. Cetin-Atalay R, Meliton AY, Wu D, Woods PS, Sun KA, Peng YJ, Nanduri J, Su X, Fang Y, Hamanaka RB, Prabhakar N, Mutlu GM. Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release. Front Physiol. 2021; 12:701995. View in: PubMed

  6. Nguyen T, Zheng M, Knapp M, Sladojevic N, Zhang Q, Ai L, Harrison D, Chen A, Sitikov A, Shen L, Gonzalez FJ, Zhao Q, Fang Y, Liao JJK, Wu R. 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

  7. Wu D, Harrison DL, Szasz T, Yeh CF, Shentu TP, Meliton A, Huang RT, Zhou Z, Mutlu GM, Huang J, Fang Y. 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

  8. Wu D, Lee TH, Huang RT, D Guzy R, Schoettler N, Adegunsoye A, Mueller J, Husain A, I Sperling A, Mutlu GM, Fang Y. SARS-CoV-2 Infection Is Associated with Reduced Krüppel-like Factor 2 in Human Lung Autopsy. Am J Respir Cell Mol Biol. 2021 08; 65(2):222-226. View in: PubMed

  9. Harrison DL, Fang Y, Huang J. T-Cell Mechanobiology: Force Sensation, Potentiation, and Translation. Front Phys. 2019 Apr; 7. View in: PubMed

  10. Lee YV, Wu D, Fang Y, Peng Y, Tian B. Tracking Longitudinal Rotation of Silicon Nanowires for Biointerfaces. Nano Lett. 2020 05 13; 20(5):3852-3857. View in: PubMed

  11. Mehta V, Pang KL, Rozbesky D, Nather K, Keen A, Lachowski D, Kong Y, Karia D, Ameismeier M, Huang J, Fang Y, Del Rio Hernandez A, Reader JS, Jones EY, Tzima E. The guidance receptor plexin D1 is a mechanosensor in endothelial cells. Nature. 2020 02; 578(7794):290-295. View in: PubMed

  12. Fang Y, Wu D, Birukov KG. Mechanosensing and Mechanoregulation of Endothelial Cell Functions. Compr Physiol. 2019 03 15; 9(2):873-904. View in: PubMed

  13. Krause MD, Huang RT, Wu D, Shentu TP, Harrison DL, Whalen MB, Stolze LK, Di Rienzo A, Moskowitz IP, Civelek M, Romanoski CE, Fang Y. 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

  14. Allon M, Litovsky SH, Tey JCS, Sundberg CA, Zhang Y, Chen Z, Fang Y, Cheung AK, Shiu YT. 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

  15. Shih YC, Chen CL, Zhang Y, Mellor RL, Kanter EM, Fang Y, Wang HC, Hung CT, Nong JY, Chen HJ, Lee TH, Tseng YS, Chen CN, Wu CC, Lin SL, Yamada KA, Nerbonne JM, Yang KC. 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

  16. Fancher IS, Ahn SJ, Adamos C, Osborn C, Oh MJ, Fang Y, Reardon CA, Getz GS, Phillips SA, Levitan I. 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

  17. Poon C, Chowdhuri S, Kuo CH, Fang Y, Alenghat FJ, Hyatt D, Kani K, Gross ME, Chung EJ. 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

  18. Wu D, Hamanaka RB, Fang Y, Mutlu GM. 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

  19. Mack JJ, Mosqueiro TS, Archer BJ, Jones WM, Sunshine H, Faas GC, Briot A, Aragón RL, Su T, Romay MC, McDonald AI, Kuo CH, Lizama CO, Lane TF, Zovein AC, Fang Y, Tarling EJ, de Aguiar Vallim TQ, Navab M, Fogelman AM, Bouchard LS, Iruela-Arispe ML. NOTCH1 is a mechanosensor in adult arteries. Nat Commun. 2017 11 20; 8(1):1620. View in: PubMed

  20. Le Master E, Huang RT, Zhang C, Bogachkov Y, Coles C, Shentu TP, Sheng Y, Fancher IS, Ng C, Christoforidis T, Subbaiah PV, Berdyshev E, Qain Z, Eddington DT, Lee J, Cho M, Fang Y, Minshall RD, Levitan I. 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

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

  22. Wu D, Huang RT, Hamanaka RB, Krause M, Oh MJ, Kuo CH, Nigdelioglu R, Meliton AY, Witt L, Dai G, Civelek M, Prabhakar NR, Fang Y, Mutlu GM. HIF-1a is required for disturbed flow-induced metabolic reprogramming in human and porcine vascular endothelium. Elife. 2017 05 30; 6. View in: PubMed

  23. 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 Krüppel-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

  24. Oh MJ, Zhang C, LeMaster E, Adamos C, Berdyshev E, Bogachkov Y, Kohler EE, Baruah J, Fang Y, Schraufnagel DE, Wary KK, Levitan I. 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

  25. Wu C, Huang RT, Kuo CH, 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. Mechanosensitive PPAP2B Regulates Endothelial Responses to Atherorelevant Hemodynamic Forces. Circ Res. 2015 Jul 31; 117(4):e41-e53. View in: PubMed

  26. Kuo CH, 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. 2014 Dec 14; 2(46):8142-8153. View in: PubMed

  27. Chung EJ, Mlinar LB, Nord K, Sugimoto MJ, Wonder E, Alenghat FJ, Fang Y, Tirrell M. Monocyte-targeting supramolecular micellar assemblies: a molecular diagnostic tool for atherosclerosis. Adv Healthc Mater. 2015 Feb 18; 4(3):367-76. View in: PubMed

  28. Davies PF, Civelek M, Fang Y, Fleming I. 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

  29. Fang Y, Davies PF. 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

  30. Fang Y, Shi C, Manduchi E, Civelek M, Davies PF. 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

  31. Davies PF, Civelek M, Fang Y, Guerraty MA, Passerini AG. 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

  32. Levitan I, Fang Y, Rosenhouse-Dantsker A, Romanenko V. Cholesterol and ion channels. Subcell Biochem. 2010; 51:509-49. View in: PubMed

  33. Mohler ER, Fang Y, Shaffer RG, Moore J, Wilensky RL, Parmacek M, Levitan I. 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

  34. Byfield FJ, Hoffman BD, Romanenko VG, Fang Y, Crocker JC, Levitan I. 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

  35. Fang Y, Mohler ER, Hsieh E, Osman H, Hashemi SM, Davies PF, Rothblat GH, Wilensky RL, Levitan I. 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

  36. Fang W, Chen JY, Fang Y, Huang JL. Epinephrine overdose-associated hypokalemia and rhabdomyolysis in a newborn. Pharmacotherapy. 2005 Sep; 25(9):1266-70. View in: PubMed

  37. Fang Y, Schram G, Romanenko VG, Shi C, Conti L, Vandenberg CA, Davies PF, Nattel S, Levitan I. 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

  38. Romanenko VG, Fang Y, Byfield F, Travis AJ, Vandenberg CA, Rothblat GH, Levitan I. Cholesterol sensitivity and lipid raft targeting of Kir2.1 channels. Biophys J. 2004 Dec; 87(6):3850-61. View in: PubMed