Academic Rank:
Professor
Afiliated with James Hogg Research Centre, Institute for Heart + Lung Health, and PROOF Centre
Affiliation(s):
Centre for Heart Lung Innovation
Location:
St. Paul’s Hospital

Short Bio:

Dr. Yang Received his Ph.D. and postdoctoral training at the University of Illinois at Urbana-Champaign. Currently, he is Professor of the Department of Pathology and Laboratory Medicine, a Member of the Center for Microbial Diseases and Host Defense Research, and a Principal Investigator of the Institute for Heart and Lung Health, UBC.

Dr. Yang’s research interests focus on two major areas. The first one is the molecular biology and pathogenesis of coxsackievirus, a positive single-stranded RNA virus. In this area of study, Dr. Yang’s laboratory is working on the mapping of the viral gene structures responsible for viral translation initiation and cardiovirulence by mutational analysis. They also identify host proteins specifically interacting with viral RNA and/or viral proteins. Based on these studies, antiviral drugs including antisense oligonucleotide, ribozyme and si/mi-RNA targeting these key genes are being developed for the treatment of coxsackievirus-induced myocarditis. To enhance the drug effectiveness, nanobiomedical approaches are employed to deliver these gene drugs specifically to certain cell populations. These drugs are being evaluated in vitro and in mouse models. The second area of Dr. Yang’s interest is the study of host gene responses to viral infection. The focus of this study is the transcriptional analysis and functional characterization of mouse genes encoding determinants of cardiac susceptibility to coxsackievirus infection. Differential mRNA display and microarray analyses have identified known and unknown candidate genes as well as microRNAs potentially involved in heart disease development. Tet-On/Off inducible cell lines and genetically modified mouse models are employed to study the roles of selected genes and microRNAs in signal transduction pathways leading to myocyte apoptosis or cardiac hypertrophy. These studies have great potential to discover new targets for gene therapy and molecular markers for diagnosis of viral myocarditis and other related infectious diseases.

Academic Backgrounds:
  • University of Illinois Postdoc. Molecular Microbiology 1989
  • University of Illinois PhD Molecular Microbiology 1986
  • University of Illinois MS Plant Pathology 1982
  • Nankai University BSc Microbiology 1978
Selected Publications
  • Zhang HM, Dai H, Hanson P, Li H, Guo H, Ye X, Hemida MG, Tong Y, Qiu Y, Liu S, Song F, Wang J, Zhang L, Yang DC.. Antiviral Activity of an Isatin Derivative via Induction of PERK-Nrf2-mediated suppression of Cap-independent Translation. ACS Chem Biol. 2014 Apr 18;9(4):1015-24. doi: 10.1021/cb400775z. Epub 2014 Feb 18.
  • Ye X, Zhang HM, Qiu Y, Hanson P, Hemida MG, Wei W, Hoodless PA, Chu F,Yang DC. Coxsackievirus-induced miR-21 disrupts cardiomyocyte interactions via the downregulation of intercalated disk components. PLoS Pathog. 2014 Apr 10;10(4):e1004070. doi: 10.1371/journal.ppat.1004070. eCollection 2014.
  • Zhang HM, Qiu Y, Ye X, Hemida MG, Hanson P, Yang DC. P58IPK inhibits coxsackievirus-induced apoptosis via the PI3K/Akt pathway requiring activation of ATF6a and subsequent upregulation of mitofusin 2. Cell Microbiol. 2014 Mar;16(3):411-24.
  • Qiu Y, Ye X, Hemida MG, Zhang HM, , Hanson PJ Yang DC. Small RNA molecules in antiviral therapy. In RNA Nanotechnology. Ed. by Wang B., Pan Stanford Publishing, USA. pp.287-307, 2014.
  • Garmaroudi FS, Marchant D, Hendry R, Luo H, Yang DC, McManus BM. Coxsackievirus B3 (CVB3) replication and pathogenesis. Future Microbiol. 2014 (in press).
  • Ye X, Hemida MG, Qiu Y, Hanson PJ, Zhang HM, Yang D. MiR-126 promotes coxsackievirus replication by mediating cross-talk of ERK1/2 and Wnt/β-catenin signal pathways. Cell Mol Life Sci. 2013 Jun 30.
  • Jensen KJ, Garmaroudi FS, Zhang J, Lin J, Boroomand S, Zhang M, Luo Z, Yang D, Luo H, McManus BM, Janes KA. An ERK-p38 subnetwork coordinates host cell apoptosis and necrosis during coxsackievirus B3 infection. Cell Host Microbe. 2013 Jan 16;13(1):67-76.
  • Wei W, Hou J, Alder O, Ye X, Lee S, Cullum R, Chu A, Zhao Y, Warner SM, Knight DA, Yang D, Jones SJ, Marra MA, Hoodless PA. Genome-wide microRNA and messenger RNA profiling in rodent liver development implicates mir302b and mir20a in repressing transforming growth factor-beta signaling. Hepatology. 2013 Jun;57(6):2491-501.
  • Hemida MG, Ye X, Zhang HM, Hanson PJ, Liu Z, McManus BM, Yang D. MicroRNA-203 enhances coxsackievirus B3 replication through targeting zinc finger protein-148. Cell Mol Life Sci. 2013 Jan;70(2):277-91.
  • Hanson PJ, Zhang HM, Hemida MG, Ye X, Qiu Y, Yang D. IRES-Dependent Translational Control during Virus-Induced Endoplasmic Reticulum Stress and Apoptosis. Front Microbiol. 2012;3:92.
  • Ye X, Hemida M, Zhang HM, Hanson P, Ye Q, Yang D. Current advances in Phi29 pRNA biology and its application in drug delivery. Wiley Interdiscip Rev RNA. 2012 Jul-Aug;3(4):469-81.
  • Liu Z, Zhang HM, Yuan J, Ye X, Taylor GA, Yang D. The immunity-related GTPase Irgm3 relieves endoplasmic reticulum stress response during coxsackievirus B3 infection via a PI3K/Akt dependent pathway. Cell Microbiol. 2012 Jan;14(1):133-46.
  • Ye X, Liu Z, Hemida MG, Yang D. Targeted delivery of mutant tolerant anti-coxsackievirus artificial microRNAs using folate conjugated bacteriophage Phi29 pRNA. PLoS One. 2011;6(6):e21215. doi: 10.1371/journal.pone.0021215.
  • Hemida MG, Ye X, Thair S, Yang D. Exploiting the therapeutic potential of microRNAs in viral diseases: expectations and limitations. Mol Diagn Ther. 2010 Oct 1;14(5):271-82.
  • Zhang HM, Ye X, Su Y, Yuan J, Liu Z, Stein DA, Yang D. Coxsackievirus B3 infection activates the unfolded protein response and induces apoptosis through downregulation of p58IPK and activation of CHOP and SREBP1. J Virol. 2010 Sep;84(17):8446-59.
  • Sall A, Zhang HM, Qiu D, Liu Z, Yuan J, Liu Z, Lim T, Ye X, Marchant D, McManus B, Yang D. Pro-apoptotic activity of mBNIP-21 depends on its BNIP-2 and Cdc42GAP homology (BCH) domain and is enhanced by coxsackievirus B3 infection. Cell Microbiol. 2010 May 1;12(5):599-614.
Research:
  • Cardiovascular & Pulmonary
  • Infectious Diseases
  • Molecular biology and pathogenesis of coxsackieviruses, a positive single-stranded RNA virus. In this area of study, Dr. Yang’s laboratory is working on the mapping of the viral gene structures responsible for viral translation initiation and cardiovirulence by mutational analysis. They also identify host proteins specifically interacting with viral RNA and/or viral proteins by gel shift assays, yeast two hybrid system and proteomic technology. Based on these studies, antiviral drugs including antisense oligonucleotide, ribozyme and si/mi-RNA targeting these key genes are being developed for the treatment of coxsackievirus-induced myocarditis. To enhance the drug effectiveness, nanobiomedical approaches are employed to deliver these gene drugs specifically to certain cell populations. These drugs are being evaluated in vitro and in animal models.
  • The study of host gene responses to viral infection. The focus of this study is the transcriptional analysis and functional characterization of mouse genes encoding determinants of cardiac susceptibility to coxsackievirus infection. Differential mRNA display and oligonucleotide microarray have identified known and unknown genes or miRNAs involved in myocarditis induction. Tet-On/Off inducible cell lines andgenetically modified mouse models are employed to study the roles of selected genes in signal transduction pathways leading to myocyte apoptosis or cardiac hypertrophy. These studies have great potential to discover new targets for gene therapy and molecular markers for diagnosis of viral myocarditis and other related infectious diseases.