Positions

Senior Staff Scientist
Virol & Micro: Zechiedrich
Baylor College of Medicine
Houston, TX, US

Education

PhD from University of Dundee
BS from University of Leeds
Postdoctoral Training at University of California at Santa Barbara
Postdoctoral Training at Baylor College of Medicine

Professional Statement

Throughout my research I have focused on how DNA is able to be an active participant in its transactions. DNA structure, particularly the structure of supercoiled DNA, is much more variable and dynamic than many people realize. This insight has allowed me to contribute to a better understanding of protein-DNA interactions and DNA itself. In the process, I have also developed unique DNA tools that are proving to be extremely useful, not only for basic research, but also clinical applications. I have developed a patented protocol to generate milligram quantities of supercoiled minicircle DNA, as small as 250 bp. Using these DNA minicircles, I precisely determine the supercoiling dependence of topoisomerase binding and additionally elucidate the mechanism through which DNA topoisomerases recognize their supercoiled DNA substrate and determine where to act. These minicircles also provide a unique insight into the structure of supercoiled DNA, including previously unappreciated differences between overwound and underwound DNA. Throughout my career I have collaborated with researchers from many disciplines including biochemistry, biophysics, physics, mathematics, structural biology, and medicine.

The development of methods to produce minicircles has proved invaluable for studying the structure of supercoiled DNA, and the enzymes that recognize and manipulate DNA supercoiling. An unexpected discovery was that these minivectors transfect cells with high efficiency and can transfect many clinically relevant cell types that are refractory to transfection with plasmid DNA. We have demonstrated that they hold great promise as a gene therapy tool. Additionally, we developed methods to capture and isolate DNA catenanes, an intermediate in the process to make minicircles. These DNA catenanes provide a means to study another very important reaction catalyzed by topoisomerases, the unlinking of catenated replication products.

Awards

Poster Prize, 11th Structural Biology Symposium (2006), Sealy Center for Structural Biology, University of Texas Medical Branch, Galveston, Texas

1st Place, Poster Prize, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Annual Retreat (2005), Baylor College of Medicine, Houston, Texas

Professional Societies

American Chemical Society (since 2005)

Biochemical Society (since 2008)

Invited Talks

Structural Diversity of Supercoiled DNA. Gordon Research Conference. DNA Topoisomerases in Biology and Medicine (2016). Sunday River, Newry, Maine.

Supercoiling in DNA minicircles: To get the big picture, think small. Banff International Research Station workshop 10w5100: Mathematics and physics of polymer entanglement (2010). The Banff Centre, Banff, Canada.

Dissecting the supercoiling dependence of topoisomerases using minicircle DNA. Topo2008: DNA Topoisomerases in Biology and Medicine (2008). John Innes Centre, Norwich, UK.

Supercoiled minicircle DNA as a probe of DNA structure and enzyme-DNA interactions. American Chemical Society southwest regional meeting (2006), Houston, Texas.

Selected Publications