The Ansari Laboratory
Faculty Aseem Z. Ansari
Aseem Z. Ansari
Associate Professor, Biochemistry
Member of the Genome Center
ansari@biochem.wisc.edu
Aligned Research Focus
Exploring gene regulation at the interface of chemistry, biology and medicine
Research Description
The major goal of my research is to create synthetic molecules that mimic natural transcription factors and can be tuned to counteract the actions of malfunctioning transcription factors. We integrate chemical, biological, biophysical, genomic and computational approaches create synthetic or artificial transcription factors (ATFs). ATFs may be engineered to control any gene regulatory circuit in a predetermined manner. In the long-term, we will create synthetic molecules that can regulate desired circuitry to dictate a desired biological outcome, for example, the fate decisions of human embryonic stem cells.
We intend to generate molecules that can be used to enforce self-renewal or programmed differentiation of stem cells. One approach would be to generate ATFs that function in lieu of the natural transcription factors that regulate pluripotency. Oct4, Sox2 and Nanog, three ES cell-specific transcription factors, are particularly attractive targets since they are essential for stem cell self-renewal and bear DNA binding domains that we have successfully mimicked with synthetic analogs. ATFs would bypass the problems inherent to the viral delivery of genes coding for the four natural transcription factors. More important, we intend to make our ATF libraries available to the stem cell community and work in synergy with interested groups.
Selected References
A. Z. Ansari (2007) “Chemical Crosshairs on the Central Dogma” Nature Chem. Biol. 3, 2-7
J. K. Lum, C. Y. Majumdar, A. Z. Ansari & A. K. Mapp (2006) “Converting Inactive Peptides into Potent Transcriptional Activators” ACS Chem. Biol. 1, 639-643
C. L. Warren, N. Kratochvil, K. E. Hauschild, S. Foister, P. B. Dervan, G. N. Phillips Jr., & A. Z. Ansari (2006) “Defining the Sequence Recognition Profile of DNA Binding Molecules” Proc. Natl. Acad. Sci. USA 103, 867-872
H. D. Arndt, K. E. Hauschild, D. P. Sullivan, K. Lake, P. B. Dervan, & A. Z. Ansari (2003) “Toward Artificial Developmental Regulators” J. Am. Chem. Soc. 125, 13322-13323
A. Z. Ansari (2003) “Fingers reach for the genome” Nature Biotechnol. 3: 242-3