B.S. Wuhan University, Wuhan, China, 1982
Ph.D. Purdue University, West Lafayette, IN, 1987
Virus Structure, Biochemistry of Viral Replication, Drug Design, Cancer Treatment
Influenza virus (IFV) continues to be a major health problem around the world. The underlining reason that IFV continues to be a major health threat is directly related to its structure. We are working on IFV proteins, including the matrix protein M1 and the ribonucleoprotein NP, to delineate the role of these proteins in re-assortment and virulence. Moreover, we are also using structure-aided approaches to design novel antiviral drugs to treat IFV infection in humans.
On a larger scale, the replication mechanism of negative strand RNA viruses (NSVs) is unique among all biological systems. NSVs include a number of important viral pathogens, such as respiratory syncytial virus (RSV), parainfluenza virus (PIV), and Ebola virus (EBV). The one factor that separates NSVs from others is that the template for viral RNA synthesis is not the genomic RNA alone, but the nucleocapsid that is formed by encapsidation of viral genomic RNA with the nucleocapsid protein. During the viral RNA synthesis, the virus-coded RNA polymerase must recognize the nucleocapsid and gain access to the sequestered RNA sequence inside the nucleocapsid in order to use it as the template for copying the RNA sequence. We have solved the structure of a large number of viral proteins and developed the new paradigm for viral RNA synthesis of NSVs. Our efforts continue to unveil the molecular mechanism of NSV replication, with an emphasis on the structure of the large subunit L in the viral polymerase. VSV may also be modified as an oncolytic drug for cancer treatment.
1989 Awarded the Sidhu Award of the Pittsburgh Diffraction Society 2007-2001 Member, study section VIRA, NIH 2013 Chair, 15th International Negative Strand Virus Meeting, session “Structure and Function”.
Sha, B.D., S.E., Phillips, V.A. Bankitas, and M. Luo. “Crystal Structure of the Saccharomyces cerevisiae phosphatidylinositol transfer protein”. Nature. 1998. 391:506-510.
Green TJ, Zhang X, Wertz GW, Luo M. “Structure of the vesicular stomatitis virus nucleoprotein-RNA complex”. Science. 2006 Jul 21;313(5785):357-60.
Ge P, Tsao J, Schein S, Green TJ, Luo M, Zhou ZH. Cryo-EM model of the bullet-shaped vesicular stomatitis virus. Science. 2010 Feb 5;327(5966):689-93.
Cox R, Pickar A, Qiu S, Tsao J, Rodenburg C, Dokland T, Elson A, He B, Luo M. Structural studies on the authentic mumps virus nucleocapsid showing uncoiling by the phosphoprotein. PNAS, 2014 Oct 21;111(42):15208-13.
Gumpper RH, Li W, Castañeda CH, Scuderi MJ, Bashkin JK and Luo M. A polyamide inhibits replication of vesicular stomatitis virus by targeting RNA in the nucleocapsid. J Virol. 2018. JVI.00146-18.
Constantinides AE, Severin CC, Gumpper RH, Zheng X and Luo M. Characterization of the PB2 cap binding domain accelerates inhibitor design. Crystals, 2018, 8(2), 62