Gender	Female
E-mail	megan.shaw@mssm.edu
Education and Training	Ph.D., University of Glasgow
	B.Sc. (Med)Honors, University of Cape Town
	B.Sc., University of Cape Town

Education and Training	Ph.D., University of Glasgow
	B.Sc. (Med)Honors, University of Cape Town
	B.Sc., University of Cape Town

Research

The Shaw laboratory is interested in the interactions that occur between RNA viruses and their hosts at the molecular level and how this knowledge may be used for designing better vaccines and for finding new antiviral drugs.  The research involves basic molecular biology and virology techniques combined with RNAi, proteomics and high-throughput screening of small molecular weight compounds.

Traditionally antiviral drugs have been designed to target viral proteins but the development of resistance is a common problem.  Viruses (particularly RNA viruses) encode a limited number of proteins and therefore they must rely on many host cell functions to complete their replication cycles.  Therefore an alternative strategy would be to direct the drug at one of these essential host factors.  The advantages of this are that the virus is far less likely to develop resistance and these drugs should also be effective against viruses that are already resistant to the current antivirals.  Furthermore, as the dependence on cellular pathways is often a conserved feature of viral replication strategies it may be possible to find a single drug that is broadly effective against several viruses.  Towards this goal, we have begun to explore the host requirements for influenza virus replication and to screen libraries of small molecules for the identification of new compounds with anti-influenza virus activity.

Another focus of the Shaw lab is the host antiviral response and specifically the mechanisms that viruses use to block this response.  Viral proteins that can inhibit the host innate immune response are important determinants of viral pathogenicity. Understanding their mechanism of action and identifying compounds that prevent their activity will aid in the design attenuated viruses for vaccine purposes or in the discovery of new antiviral drugs.  One virus of particular interest to us is Nipah virus, with is a highly pathogenic, emerging paramyxovirus.  Nipah virus encodes multiple proteins that inhibit the antiviral response and in collaboration with the Basler laboratory, our goal is to determine their mechanisms of action and their individual contributions to virus pathogenesis.  In collaboration with the Palese and Garc­a-Sastre laboratories, we are also investigating the immune-evasion activity of the influenza virus NS1 protein as a new target for potential influenza antiviral drugs.

Hoffmann HH, Palese P, Shaw ML. Modulation of influenza virus replication by alteration of sodium ion transport and protein kinase C activity. Antiviral Research 2008; 80: 124-134.

Shaw ML, Stone KL, Colangelo CM, Gulcicek EE, Palese P. Cellular Proteins in Influenza Virus Particles. PLoS Path 2008; 4(6): e1000085.

Reid SP, Leung LW, Hartman AL, Martinez O, Shaw ML, Carbonelle C, Volchkov VE, Nichol ST, Basler CF. Ebola virus VP24 binds karyopherin α1 and blocks STAT1 nuclear accumulation. J. Virol 2006; 80: 5156-5167.

Shaw ML, Cardenas WB, Zamarin D, Palese P, Basler CF. Nuclear localization of the Nipah virus W protein allows for inhibition of both virus- and TLR3-triggered signaling pathways. J. Virol 2005; 79: 6078-6088.

Shaw ML, Garcia-Sastre A, Palese P, Basler CF. Nipah virus V and W proteins have a common STAT1-binding domain yet inhibit STAT1 activation from the cytoplasmic and nuclear compartments respectively. J. Virol 2004; 78: 5633-5641.

Park MS, Shaw ML, Munoz-Jordan J, Cros J, Nakaya T, Bouvier N, Palese P, Garcia-Sastre A, Basler CF. A Newcastle disease virus (NDV) based assay demonstrates interferon-antagonist activity for the NDV V protein and the Nipah virus V, W and C proteins. J. Virol 2003; 78: 1501-1511.

Shaw ML, McLauchlan J, Mills PR, Patel AH, McCruden E. Characterization of the differences between hepatitis C virus genotypes 3 and 1 glycoproteins. J. Med. Virol 2003; 70: 361-372.

Cochrane A, Orr A, Shaw ML, Mills PR, McCruden EA. The amino acid sequence of the PKR-elF2 alpha phosphorylation homology domain of hepatitis C virus envelope 2 protein and response to interferon-alpha. J. Infect. Dis 2000; 182: 1515-1518.

Shaw ML, Palese P. Orthomyxoviruses: Molecular biology. In: Mahy B, van Regenmortel M, editors. Encyclopedia of Virology 3rd edition . Oxford, U.K, Elsevier; pp483-489.

Palese P, Shaw ML. Orthomyxoviridae: The Viruses and Their Replication. In: Knipe DM, Howley PM, editors. Fields Virology 5th edition . Philadelphia, Lippincott Williams & Wilkins; pp1647-1689.