Professor, Biological Sciences
M.S. and Ph.D. Degrees in Biochemistry, University of Georgia, Athens, Georgia, 1978
B.S. Degree in Chemistry, Eckerd College, St. Petersburg, Florida, 1972
Website: Dr. Sinden's Website
Professional Experience
2006: Professor, Department of Biological Sciences, Florida Tech
2001-2005: Associate Director, Institute of Biosciences and Technology (IBT) Texas A&M University System Health Science Center, Houston
1999: Professor, IBT, TAMHSC, Houston
1992: Associate Professor, IBT, TAMU, Houston
1991: Associate Professor, Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, College of Medicine, Cincinnati, Ohio
1984 Assistant Professor, Department of Biochemistry and Molecular Biology, University of Cincinnati, College of Medicine, Cincinnati, Ohio
Research Interests
Research in the Sinden lab comprises two overlapping areas. The first area involves the biology of DNA structure (as summarized in my textbook DNA STRUCTURE AND FUNCTION (1994) Academic Press). We characterize supercoiled DNA as organized into independent topological domains in living cells and alternative DNA structures that require supercoiling for fomration. A second area of interest involves understanding spontaneous mechanisms of mutagenesis, which result in cancer and human disease. We utilize techniques ranging from biophysics to cell and molecular biology.
Current Research
DNA Structure and Supercoiling: We study unusual DNA structures and DNA supercoiling. We have studied many “alternative” conformations of DNA, including cruciforms, left-handed Z-DNA, intramolecular triplex DNA, and unwound DNA structures. In 1995 we discovered a new alternative DNA structure called slipped-strand DNA. We have shown that many of these structures exist in the chromosomes of living bacterial cells. We work to understand the biological roles of these alternative DNA conformations in mammalian cells.
Molecular Mechanisms of Spontaneous and Genotoxicant-induced Mutation: A second area of research interest involves understanding the molecular mechanisms of mutagenesis. An exciting correlation exists between DNA sequences that form alternative structures and mutations that cause cancer and human genetic disease. That is – mutations do not really occur randomly, rather they are often templated by the DNA sequence itself. In other words, certain DNA sequences (DNA repeats) are their own worst enemy. These DNA sequences are prone to, or better perhaps, programed for, self-directed mutation. We work to understand these molecular mechanisms of spontaneous mutagenesis that involve alternative DNA conformations. In addition, we have shown that many types of mutations occur preferentially on either the leading or lagging strand during replication.
DNA Repeat Instability Associated with Human Genetic Neurodegenerative Disease: A third area of interest involves understanding the molecular basis of certain human genetic diseases. This area of research integrates the above two focus areas: DNA structure and spontaneous mutagenesis. Currently, more than 40 human genetic neurodegenerative diseases are caused by the massive expansion of (CTG)n•(CAG)n, (CGG)n•(CCG)n, (GAA)n•(TTC)n, (CCTG)n•(CAGG)n, or (ATTCT)n•(AGAAT)n DNA repeats. All these DNA repeats form one or more alternative DNA conformations, including hairpins, slipped strand DNA, parallel DNA, triplex DNA, and unwound structures, which are likely involved in their genomic instability (i.e., expansion or deletion mutations). We have developed genetic assays for studying the deletion of DNA repeats in a model bacterial system. A goal of our laboratory is to understand the molecular basis for the expansion (and deletion) mutations and to find a therapeutic approach for reducing repeat length. With such an approach, one may be able to prevent or delay onset of repeat expansion diseases.