ResearchAlthough the sequence of the human genome has been disclosed, mechanisms of the reading of the genome are not fully understood. Transcription (the reading of the genome) and its regulation underlies fundamental processes such as morphogenesis, differentiation and cancer. The focus of our lab is to understand the mechanisms of transcription and its regulation as it relates to cancer. Indeed transcription factors such as P53, BRCA1, EWS/Fli1 and many others are now known to function through altering transcription in the cell. We therefore believe that understanding transcription will allow an understanding of the fundamental processes involved in cancer. Furthermore, targeting improper transcription mechanisms occurring in cancer cells will allow for the development of new and more direct therapies for cancer.
Our research is currently focussed on the motor of transcription, RNA polymerase II and its direct modulation by transcription factors. One such factor, TFIIS, is crucial in allowing for RNA polymerase II to efficiently generate full length mRNA. It has also been implicated in tumorigenesis. Our main goals are to determine how RNA Polymerase II functions, how it is regulated by transcription factors like TFIIS and how that regulation is altered in cancer.
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Lab TechniquesWe employ a broad range of techniques. It is our belief that research is the goal and that any technique needed to achieve an understanding of the problem will be performed. As such we use molecular biology (DNA/RNA work, genearray technology, PCR etc.), Biochemistry (protein purification, biochemical assays etc) and x-ray crystallography (to determine the structure of key components in the transcription apparatus).
PublicationsCramer, P., Bushnell, D.A., Fu, J., Gnatt, A.L., Maier-Davis, B., Thompson, N.E., Burgess, R.R., Edwards, A.M., David, P.R., and Kornberg, R.D., (2000) Architecture of RNA Polymerase II and implications for the transcription mechanism. Science 288:640-9.
Fu, J., Gnatt, A., Bushnell, D., Jensen, G.J., Thompson, N.E., Burgess, R.T., David, P., and Kornberg, R.D (1999). Yeast RNA polymerase II at 5 Resolution. Cell 98:799-810.
Fu, J., Gerstein, M., David, P., Gnatt, A., Bushnell, D., Edwards, A.M., and Kornberg, R.D., (1998) Repeated tertiary fold of RNA polymerase II and implications for DNA Binding. J.Mol. Biol. 280:317-32.
Gnatt, A., Cramer, P., Fu, J., Bushnell, D., and Kornberg, R., (2001) Structural basis of transcription: an RNA Polymerase II elongation complex at 3.3 Resolution. Science (accepted for publication in June).
Gnatt, A., Fu, J. and Kornberg, R.D. (1997) Formation and crystallization of yeast RNA polymerase II elongation complexes. J. of Biol. Chem. 272:30799-30805.
Poglitsch, C.L., Meredith, G.D., Gnatt, A., Jensen, G.J., Chang, W., Fu, J., and Kornberg R. (1999). Electron crystal structure of an RNA polymerase II transcription elongation complex. Cell 98:791-798.
Svejstrup, Q. J., Li, Y., Fellows, J., Gnatt, A., Bjorklund, S., and Kornberg, R.D. (1997) Evidence for a mediator cycle at the initiation of transcription. Proc. Natl. Acad. Sci. USA 94:6075-6078.
Personal History
- Bar-Ilan University, Ramat-Gan, Israel, BSc.,1980-1984,Biology
- Weizmann Institute of Science, Rehovot, Israel, MSc.,1984-1986,Neurobiology
- Hebrew University of Jerusalem, Givat-Ram, Israel, PhD,1986-1991,Biochemistry
- Stanford University, Stanford, California ,Postdoc,1992-1999,Structural Biology
Laboratory PersonnelGraduate Students:
- Jennifer Catallano
- Kyle Hubbard
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