Sherie L. Morrison
Research in our laboratory is directed towards acquiring a greater understanding of antibody structure, function and regulation, and using this information to produce antibodies with novel functional properties.
Vectors have been created for the expression of recombinant antibody genes in eukaryotic cells. The resulting antibodies are used to investigate structural features which contribute to functional properties of human antibodies of different isotypes. This experimental approach can be utilized to produce large quantities of pure proteins otherwise available only in limiting quantities such as human IgD and the different rare isoforms of IgE. An advantage of producing antibodies by gene transfection techniques is that one is no longer limited to producing antibodies as they occur in nature. We can now produce antibodies with novel functional properties. These include antibodies with increased ability to carry out certain effector function, antibodies fused to growth factors and antibodies with novel carbohydrate structures. Antibody-growth factor fusion proteins have unique properties, including increased ability to cross the blood-brain-barrier. Antibodies fused with cytokines such as Interleukin-2 potentially can be used to target immune activation to desired locales such as the site of a tumor. Constant region carbohydrate is essential for some effectors functions, and variable region carbohydrate can influence the ability of the antibody to interact with antigen; we are defining the influence of carbohydrate structure on antibody function. These experiments are important both for our understanding of antibody function and for our ability to effectively utilize antibodies as diagnostic and therapeutic agents.
Experiments are also in progress to investigate the regulation of the tissue specific expression of antibody genes.
Selected Recent Publications:
Chintalacharuvu, K.R., Raines, M.B., and Morrison, S.L. Divergence of human a chain constant region gene sequences: A novel recombinant a gene. J. Immunol. 152:5299-5304, 1994.
Chou, C.L., and Morrison, S.L. Intron sequences determine the expression of Kappa Light Chain genes. Molecular Immunology 31:99-107, 1994.
Snyder, J.G., Dinh, Q., Morrison, S.L., Padlan, E.A., Mitchell, M., Yu-Lee, L.Y., and Marcus, D.M. Structure-function studies of Anti-3-Fucosyllactosamine and Anti-Galactosylgloboside antibodies. J. Immunol. 153:1161-1170, 1994.
Morrison, S.L. News and View: Success in Specification. Nature 368:812-813, 1994.
Batra, S.K., Niswonger, M.L., Wikstrand, C.J., Pegram, C.N., Zalutsky, M.R., Morrison, S.L., and Bigner, D.D. Mouse/Human chimeric Mel-14 antibody: Genomic cloning of the variable region genes, lindage to human constant region genes, expression and characterization. Hybridoma 13:87-97, 1994.
Morrison, S.L., Smith, R.I.F., and Wright, A. Structural determinants of human IgG function. The Immunologist 2(4):119-124, 1994.
Chintalacharuvu, K.W. and Morrison, S.L. Production of secretory immunoglobulin A by a single mammalian cell. Proc. Natl. Acad. Sci..94:6364-6368, 1997.
Wright, A. and Morrison, S.L. Effect of CH2-associated carbohydrate structure on Ig effector function: Studies with chimeric mouse-human IgG1 antibodies in g ylation mutants of Chinese hamster ovary cells. J. Immunol. 160:3393-3402, 1998.
Mohammed, S.M., Bonselaar, J., Morrison, S., Wims, L., Trinh, KR., and Etches, R.J. Deposition of genetically engineered human antibodies into the egg yolk of hens. Immunotechnology, 4:115-126, 1998.
Peng, L.S., Penichet, M.L., and Morrison, S.L. A single-chain IL-12 IgG3 antibody fusion protein retains antibody specificity and IL-12 bioactivity. J. Immunol., 163:250-258, 1999.
Penichet, M.L., Kang, Y.-S., Pardridge, W.M., Morrison, S.L., and Shin, S.-U. An anti-transferrin receptor antibody-avidin fusion protein serves as a delivery vehicle for effective brain targeting J. Immunol 163:4421-4426, 1999.
Yoo, E.M., Coloma, J., Trinh, K.R., Nguyen, T.Q., Vuong, L-U. C., Morrison, S.L., and Chintalacharuvu, K.R. Structural requirements for polymeric immunoglobulin assembly and association with J chain. J. Biol. Chem. 274:33771-7.
Coloma, M.J., Lee, H.J., Kurihara, A., Landaw, E.M., Boado, R.J., Morrison, S.L., and Pardridge, W.M. Transport across the primate blood-brain barrier of a genetically engineered chimeric monoclonal antibody to the human insulin receptor, Pharmaceutical Res. 17:265-273, 2000.
Rifai, A., Fadden, K., Morrison, S.L., and
Chintalacharuvu, K.R. The N-glycans determine the differential
blood clearance and hepatic uptake of human IgA1 and IgA2 istoypes.
In press, J. Exp. Med.