I trained in X-ray crystallography, biochemistry, and computation. With this foundation, I contributed to structural biochemistry for the biology for DNA repair, reactive oxygen control, the immune response, and other stress responses for >20 years. Our NCI-funded papers report robust structural and biophysical measurements to advance understanding of cellular stress responses that are evolutionarily conserved and important in preserving genome stability and preventing diseases in humans. My methods, results, and concepts have stood the test of time: they are often used and cited >30,000 total times.

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I trained in X-ray crystallography, biochemistry, and computation. With this foundation, I contributed to structural biochemistry for the biology for DNA repair, reactive oxygen control, the immune response, and other stress responses for >20 years. Our NCI-funded papers report robust structural and biophysical measurements to advance understanding of cellular stress responses that are evolutionarily conserved and important in preserving genome stability and preventing diseases in humans. My methods, results, and concepts have stood the test of time: they are often used and cited >30,000 total times.

At Scripps, I created and ran the Scripps NSF Computational Center for Macromolecular Structure along with an NIH P01 on Metalloprotein Structure and Design. I also helped develop and utilize the Scripps share of the NSF San Diego Supercomputer Center. At LBL, I developed and directed the ~$2.9 million/year DOE Program “Molecular Assemblies Genes and Genomics Integrated Efficiently” (MAGGIE) from 2004-2011.

At Berkeley, I designed, developed, and directed the world’s only dual endstation synchrotron beamline SIBYLS (Structurally Integrated BiologY for Life Sciences), used by >200 NIH labs. This unique technology integrates high flux small angle x-ray scattering (SAXS) and macromolecular X-ray crystallography (MX). At SIBYLS we develop, optimize, and apply technologies to determine accurate structures, conformations and assemblies both in solution and at high resolution. We defined an R-factor gap in MX revealing an untapped potential for insights on nanoscale structures by better modeling of bound solvent and flexible regions.

At the University of Texas MD Anderson Cancer Center, I am joining biochemistry and biophysics to fluorescent imaging measures of protein and RNA interactions on DNA for mechanistic insights. I am integrating these data with cryo-EM, MX and SAXS structures by linking my MD Anderson and SIBYLS facilities.

As an originator of applying proteins from thermophiles to defining dynamic structures and functional conformations, I develop methods for measurements on structures including conformations, and assemblies in solution. I have combined cryo-EM and X-ray structures with biochemistry to define functional assemblies. We introduced new equations for analyzing X-ray scattering for flexible macromolecules and complexes. We defined a novel SAXS invariant: the first discovered since the Porod invariant ~60 years ago. Our defined parameters quantitatively assess flexibility, measure intermolecular distances, determine data to model agreement, and reduce false positives.

I have a track record of successful collaborations, completing projects, sharing innovating approaches and technologies, developing insights along with new structural data, and providing fundamentally important technologies that improve the ways others do their research. I have benefited from continuous peer-reviewed NCI funding since 1999. NCI support has allowed me to develop expertise in the methods development and in the structural biology of DNA repair, immune responses, and other stress.

CPRIT is transformative to my efforts on DNA damage response inhibitors and interactomes by enabling me to unite my skills, systems, and technologies into a major contribution of repair structural mechanisms that inform cancer biology. The results promise to build foundational knowledge on DNA damage responses and their connections to profoundly impact understanding for cancer biology impacting patient care.

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