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Luis Schang

Schang70.jpg
Professor
MV, University of Buenos Aires, 1982-1987
PhD, University of Nebraska-Lincoln, 1991-1995
PDF, University of Pennsylvania, 1996-2000

Department of Biochemistry
Faculty of Medicine & Dentistry
University of Alberta
6-142G  Katz Group – Rexall Centre for Pharmacy and Health Research
Edmonton, Alberta, Canada  T6G 2E1
 
Tel: 780.492.6265
Lab Tel: 780.492.6606
Fax:  780.492.3383
 
 
Research:
 
Our lab is interested on the roles that cellular proteins, lipids, and glycans play in viral infection, replication and pathogenesis, with the ultimate goal of finding novel antiviral drugs.
 
We use chemical virology as the main approach to study virus-cell interactions. This approach consists in using carefully selected small molecular probes to interrogate virus-infected cells. We usually select novel (experimental) drugs or natural compounds to test well supported hypotheses on the requirement of cellular proteins, glycans or lipids in viral replication. We then follow the probes with the most interest activities, identifying and characterizing molecules and functions required for viral infection, replication, or pathogenesis.
 
In our studies, we use standard and state-of-the-art virology, biochemistry, imaging and molecular and cell biology techniques. We have ample expertise in the study of infectivity, spread and gene expression of a variety of DNA or RNA viruses, including herpesviruses, HCV, influenza virus, poxviruses, Sindbis virus, adenovirus, and many others. We collaborate with many groups in Canada, the USA, and Europe.
 
Viral infection starts with the entry of extracellular virions into cells, a function that is considered a desirable target for antiviral drugs. Current clinical entry inhibitors target the viral proteins involved in this process. They are consequently restricted by certain intrinsic limitations of targeting viral proteins. For example, drugs targeting viral proteins promptly select for drug-resistant virus variants. We have identified a novel family of viral entry inhibitors with unique mechanisms of action and targets, which are not limited by prompt selection for resistance. We have named them RAFIs. We are now further characterizing them, their mechanisms of action, and their potential to be developed as antivirals. We also discovered the antiviral mechanisms of a natural compound in green tea, so called EGCG, and we are developing novel synthetic and compounds to inhibit viral entry.
 
We continue searching for new chemical probes with interesting activities on viral infectivity and spread. We have identified one that most surprisingly inhibits cell-to-cell spread of hepatitis C virus (HCV), but not the infectivity of cell-free HCV virions. We have identified that these compounds have a most unique mechanism of action, and are in the process of identifying their molecular targets.
 
Using chemical virology approaches, we discovered some years ago that certain cellular protein kinases are required to activate transcription form the extra-chromosomal herpesviral genomes. In characterizing the antiviral mechanisms of these inhibitors, we have found a new innate cellular defense mechanisms against viral infections, chromatin silencing. Viruses have therefore evolved mechanisms to counteract these antiviral defenses. The viral counteraction results in the activation of viral transcription. We are currently analyzing the mechanisms of this cellular silencing-viral counter-silencing interaction.
 
We are currently interested in five major areas of research: 1) the mechanisms whereby cellular chromatin affects the transcription of viral genes; 2) the mechanisms whereby viruses counteract the inhibition of gene expression by chromatin; 3) the full characterization of the potential of the RAFIs as antiviral drugs; 4) the identification of novel antiviral compounds and the characterization of the mechanisms of action of synthetic and natural antiviral compounds, and 5) the potential of inhibitors of cellular proteins required for replication or pathogenesis of infectious agents as anti-infective drugs.
 
Lab Members:

Abdullah Awadh, Graduate Student
Kristen Conn, Research Associate
Rachael Erdmann, Research Technician
Esteban Flores, Graduate Student
Evgeni Gabev, Postdoctoral Fellow
Rebecca Gibeault, Graduate Student
Mi-Yao Hu, Graduate Student
Furkat Mukhtarov, Graduate Student
Bizhan Romani, Postdoctoral Fellow​
Sietske Speerstra, Graduate Student
Brendan Todd, Graduate Student

Selected Recent Publications:

Colpitts, CC, and Schang, LM (2014)A small molecule inhibits attachment to heparan sulfate- or sialic acid-containing glycans Journal of Virology 88 (14): 7806-7817.
 
Conn, KL, Hendzel, M, and Schang, LM (2013)The Differential Mobilization of Histones H3.1 and H3.3 by Herpes Simplex Virus 1 Relates Histone Dynamics to the Assembly of Viral ChromatinPLOS Pathogens 9(10): e1003695.
 
Colpitts, CC, Ustinov, A, Epand, RA, Epand, RM, Korshun,VA and Schang, LM (2013) 5-(Perylen-3-yl)ethynyl-arabino-uridine (aUY11), an arabino-based rigid amphipathic fusion inhibitor, targets virion envelope lipids to inhibit fusion of influenza, hepatitis C and other enveloped viruses Journal of Virology 87 (7): 3640-3654
 
Lacasse, JJ, and Schang, LM (2012) “Herpes Simplex Virus 1 DNA Is in Unstable Nucleosomes throughout the Lytic Infection Cycle, and the Instability of the Nucleosomes Is Independent of DNA Replication”. Journal of Virology 86 (20): 11827-11300.
 
Conn K, Hendzel M, and Schang LM (2011) “Core histones H2B and H4 are mobilized during infection with herpes simplex virus type 1 (HSV-1)” Journal of Virology 85 (24): 13234-52.
 
St.Vincent MR, Colpitts C, Ustinov AV, Muqadas M, Joyce M, Barsby N, Epand R, Epand R, Khramyshev AS, Valueva OA, Korshun VA, Tyrrell L; and Schang LM(2010) “Rigid amphipathic fusion inhibitor, RAFI, small molecule antiviral compounds active against HCV, HSV, and other enveloped viruses”.  Proceedings of the National Academy of Sciences, USA (PNAS) 107(40):17339-17344.
  
 
Recent Patents:
Schang, LM, StVincent, MRS; and Ustinov, A “Compounds for preventing or treating viral infections and methods of use thereof” Granted in the USA, China, Japan, and the European Union.