• B.S., Nanjing University, Nanjing, P.R. China
• Ph.D., University of Mississippi Medical Center
• Postdoctoral training, Johns Hopkins University
Our laboratory focuses on studying how transcription affects DNA structural changes and activates or inhibits nearby promoters. Using defined protein systems and in vivo E. coli cells, we found that transcription is a major chromosome remodeling force in bacteria at exponential phase and certain DNA binding proteins, such as FIS and HU, function as topological barriers to modulate localized DNA supercoiling stemming from transcription. We are also utilizing our in vitro and in vivo systems derived from these basic studies to identify or discover antibiotics targeting bacterial DNA gyrase.
A second project in our laboratory focuses on studies of the mammalian high mobility group protein AT-hook 2 (HMGA2), a nuclear transcription factor associated with many physiological functions including oncogenesis, obesity, stem cell youth, human height, and human intelligence. This protein contains three “AT hook” DNA binding motifs and specifically recognizes the minor groove of AT-rich DNA sequences. We are particularly interested in understanding the structures and functions of this intriguing protein, and hope to use our knowledge from this basic research to discover or identify small molecular compounds to combat cancers by targeting HMGA2-DNA interactions.
• Fulcrand, G., Dages, S., Zhi, X., Chapagain, P., Gerstman, B. S., Dunlap, D., and Leng, F. DNA supercoiling, a critical signal regulating the basal expression of the lac operon in Escherichia coli. Scientific Reports, 2015, in press.
• Aloso, N., Guillin, R., Chambers, J, and Leng, F. A rapid, sensitive high throughput screening method to identify compounds targeting protein-nucleic acids interactions. Nucleic Acids Research, 2015, 43(8): e52.
• Ding, Y., Manzo, C., Fulcrand, C., Leng, F., Dunlap, D., and Finzi, L. DNA Supercoiling: a Regulatory Signal for the Lambda Repressor. Proceedings of the National Academy of Sciences U S A, 2014, 111: 15402-15407.
• Leng, F., Chen, B. and Dunlap, D. Dividing a supercoiled DNA molecule into two independent topological domains, Proceedings of the National Academy of Sciences U S A, 2011, 108, 19973-19978.
• Chen, B., Xiao, Y., Liu, C., Li, C., and Leng, F. Protein-Induced DNA Linking Number Change by Sequence-Specific DNA-Binding Proteins. Nucleic Acids Research, 2010, 38, 3643-3654.
• Cui, T. and Leng, F. Specific Recognition of AT-Rich DNA Sequences by the Mammalian High Mobility Group Protein AT-hook 2: A SELEX Study. Biochemistry, 2007, 46, 13059-13066.
• Samul, R. and Leng, F. Transcription-coupled Hypernegative Supercoiling of Plasmid DNA by T7 RNA Polymerase in Escherichia coli Topoisomerase I-Deficient Strains. Journal of Molecular Biology, 2007, 374, 925-935.