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Faculty Detail    
Name LOUISE T CHOW
 
Campus Address MCLM 510 Zip 0005
Phone 205-975-8300
E-mail ltchow@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Professor
Center  Center for Aging  COMPREHENSIVE CTR FOR HEALTHY AGING Professor
Center  Center for AIDS Research  Center for AIDS Research Professor
Center  Center for Biophysical Sciences/Engineering  Center for Biophysical Sciences/Engineering Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Cystic Fibrosis Research Center  Cystic Fibrosis Research Center Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Medical Scientist Training Program 
Microbiology 

Biographical Sketch 
1973 PhD in Chemistry, California Institute of Technology (Caltech), Norman Davidson, advisor. She investigated genome organization of bacterial phages and bacterium using the heteroduplex-electron microscopy method. 1973-74, post doctoral training, UC San Francisco and Caltech. 1975, Fellow, Cold Spring Harbor Laboratory; 1976 Staff investigator; 1977 senior staff investigator; 1979, senior scientist with tenure. At CSHL, she continued to use heteroduplex-electron microscopy to study phage and viral genome organization and regulation as well as cellular gene structure. Her work led to the first discovery that DNA inversion regulates gene expression in the phage Mu system (Kamp et al., 1978). She was the lead author for the work reporting the discovery of mRNA splicing in adenovirus (Chow et al., 1977). This work was awarded the Nobel Prize in Physiology or Medicine in 1993 to her collaborator R.J. Roberts and P.A. Sharp of MIT. 1984-93, associate professor and professor of Biochemistry at University of Rochester. 1993-current, UAB.

Society Memberships
Organization Name Position Held Org Link
ASM  member   

Research/Clinical Interest
Title
Human papillomavirus DNA replication and pathogenesis
Description
My lab has been working on human papillomaviruses (HPV) for almost 2 decades. HPVs are prevalent and medically important human pathogens. The genome consists of a circular double-stranded DNA of 8 kbp. Infections by the mucosotropic HPV types cause anogenital condylomata and laryngeal papillomas. Infections by the high-risk HPVs can progress to dysplasia and cancinoma, notably, cervical, penile and anal cancers. Research in the lab spans the basic biology and pathobiology of these viruses. By examining patient specimens with in situ methods, we discovered that the productive phase of the virus infection takes place only in differentiated cells of a squamous epithelium. Thus, we develop organotypic cultures of primary human keratinocytes (PHKs) in which the cells stratify and differentiate into skin in vitro. Using this system, our lab produced HPV in vitro for the first time. By combining this culture system and retrovirus-mediated gene transfer, we have been investigating the functions of individual viral genes and the regulation of the viral promoters. We recently developed an efficient method to produce high titers of infectious HPV virus and recapitulated for the first time productive infections in PHK raft cultures. Using this new system, we are conducting genetic analysis of oncogeneic and non-oncogenic HPV typres. We also study the regulation of HPV DNA replication and the mechnaism of HPV DNA partitioning during cell division for persistent infection.

Selected Publications 
Publication PUBMEDID
Chow, L.T. and T. R. Broker. 2007. Human papillomavirus RNA transcription. In, The Papillomaviruses (Eds: D. DiMaio and R. Garcea). pp.109-131. Kluwer Academic/Plenum Publishers.   
Deng, W., B.-Y. Lin, G. Jin, C.G. Wheeler, T. Ma, J.W. Harper, T.R. Broker and L.T. Chow. 2004. Cyclin/CDK regulates the nucleo-cytoplasmic localization of the human papillomavirus E1 DNA helicase. J. Virol. 78: 13954-13965.   
Yu, J-H. B. Y. Lin, W. Deng, T.R. Broker, and L.T. Chow. 2007. MAPKs activate the nuclear localization sequence of the HPV-11 E1 DNA helicase to promote efficient nuclear import. J. Virol. In Press.   
Banerjee, N.S, N.Genovese, F. Noya, W.-M. Chien, L.T. Chow, and T.R Broker. 2006. Inducible E7 proteins of high-risk and low-risk HPVs promote S phase re-entry in post-mitotic differentiated keratinocytes in organotypic cultures. J. Virol. 80: 6517-6524.   
Dao, L.D., A. Duffy, B.A.Van Tine, S.-Y. Wu, C.-M. Chiang, T.R. Broker, and L.T. Chow. 2006. Dynamic localization of the HPV-11 origin binding protein E2 during mitosis while in association with the spindle apparatus. J. Virol. 80: 4792-4800.   
Deng, W., B.-Y. Lin, G. Jin, C. Wheeler, T. Ma, J.W. Harper, T.R. Broker and L.T. Chow. 2004. Cyclin/CDK regulates the nucleo-cytoplasmic localization of the human papillomavirus E1 DNA helicase. J. Virol. 78: 13954-13965.   
Banerjee, N.S., A.A. Rivera, M. Wang, L.T. Chow, T.R. Broker, D.T. Curiel and D.M. Nettelbeck. 2004. Analyses of melanoma-targeted oncolytic adenoviruses with tyrosinase enhancer/ promoter - driven E1A, E4, or both in submerged cells and in organotypic cultures. Mol. Cancer Therapeutics 3: 437-449.   
Noya, F., C. Balagué, N.S. Banerjee, D.T. Curiel, T.R. Broker and L.T. Chow. 2003. Activation of adenovirus early promoters and lytic phase in differentiated strata of organotypic cultures of human keratinocytes. J. Virol. 77: 6533-6540.   
Chow, L. T., and T.R. Broker. 2006. Papillomavirus. In, DNA Replication and Human Disease (Ed: M. DePamphilis). pp.609-625. Cold Spring Harbor Laboratory Press.    
Chow, L.T. and T.R. Broker. 2006. Mechanisms and regulation of papillomavirus DNA replication. In, Papillomavirus Research: From Natural History to Vaccines and Beyond (Ed: M.S. Campo). pp.53-71. Caister Academic Press.   
Kamp, D., R. Kahmann, D. Zipser, T.R. Broker and L.T. Chow. 1978. Infectivity of phage Mu depends on the orientation of the invertible G DNA segment. Nature 271: 577 580.   
Van Tine, B.A., L.D. Dao, S.-Y. Wu, T.M. Sonbuchner, B-Y. Lin, Nianxiang Zou, C.-M. Chiang, T.R. Broker, L.T. Chow. 2004. HPV origin binding protein associates with mitotic spindles to enable viral DNA partitioning. Proc. Natl. Acad. Sci. USA. 101. 4030-4035.   
Van Tine, B.A, J.C. Kappes, N.S. Banerjee, J. Knops, L. Lai, R.D.M. Steenbergen, C.L.J.M. Meijer, P.J.F. Snijders, P. Chatis, T.R. Broker, P.T. Moen, Jr. and L.T. Chow. 2004. Clonal selection for transcriptionally active viral oncogenes during progression to cancer by DNA methylation-mediated silencing. J. Virol. 78: 11172-11186.   
Banerjee, N.S., A.A. Rivera, M. Wang, L.T. Chow, T.R. Broker, D.T. Curiel and D.M. Nettelbeck. 2004. Analyses of melanoma-targeted oncolytic adenoviruses with tyrosinase enhancer/ promoter - driven E1A, E4, or both in submerged cells and in organotypic cultures. Mol. Cancer Ther. 3. 437-449.   
Deng, W., G. Jin, B.-Y. Lin, B.A. Van Tine, T.R. Broker and L.T. Chow. 2003. mRMA splicing regulates human papillomavirus type 11 E1 protein production and DNA replication. J. Virol. 77: 10213-10226.   
Lin, B.-Y., A.M. Makhov, J.D. Griffith,T.R. Broker, and L.T. Chow. 2002. Human chaperone proteins abrogate inhibition of the human papillomavirus (HPV) E1 helicase by the HPV E2 protein. Mol. Cell. Biol. 18: 6591-6603.   
Chien, W-M., F. Noya, H.M. Benedict-Hamilton, T.R. Broker, and L.T. Chow. Alternative fates of keratinocyts transduced by human papillomavirus tyep18 E7 during squamous differentiation. 2002. J. Virol. 76: 2964-2972.   
Balagué, C., F. Noya, R. Alemany, L.T. Chow, and D.T. Curiel. 2001. Human papillomavirus E6E7 mediated cytolysis by an adenovirus mutant: selective replication ascertained in organotypic cultures of human keratinocytes. J. Virol 75:7602-7611.   
Noya, F., W.-M. Chien, T.R. Broker, and L.T. Chow. 2001. p21cip1 degradation in differentiated keratinocytes is abrogated by co-stabilization with cyclin E induced by HPV E7. J. Virol. 75: 6121-6134.   
Ma, T., B.A. Van Tine, W. Yue, M. Garrett, D. Nelson, P.D. Adams, J. Wang, J. Qin, L.T. Chow, and J.W. Harper. 2000. Cell cycle-regulated phosphorylation of p220NPAT by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription. Genes Dev. 14: 2298-2313.   
Cheng, S., D.-C. Schmidt-Grimminger, T. Murant, T.R. Broker, and L.T. Chow. 1995. Differentiation-dependent up-regulation of the human papillomavirus E7 gene reactivates cellular DNA replication in suprabasal differentiated keratinocytes. Genes & Development 9: 2335-2349, plus cover.   
Kuo, S.-R., J.S. Liu, T.R. Broker, and L.T. Chow. 1994. Cell-free replication of the human papillomavirus DNA with homologous viral E1 and E2 proteins and human cell extracts. J. Biol. Chem. 269: 24058-24065   
Dollard, S.C., J.L. Wilson, L.M. Demeter, W. Bonnez, R.C. Reichman, T.R. Broker, and L.T. Chow. 1992. Production of human papillomavirus and modulation of the infectious program in epithelial raft cultures. Genes & Development 6: 1131-1142, plus cover.   
Chiang, C.-M., M. Ustav, A. Stenlund, T.F. Ho, T.R. Broker, and L.T. Chow. 1992. Viral E1 and E2 proteins support replication of homologous and heterologous papillomaviral origins. Proc. Natl. Acad. Sci. USA 89: 5799-5803.   
Chow, L.T., R.E. Gelinas, T.R. Broker, and R.J. Roberts. 1977. An amazing sequence arrangement at the 5' ends of adenovirus 2 messenger RNA. Cell 12: 1 8, plus cover.   

Keywords
HPV infections and cancers