Professor, Department of Molecular and Cellular Oncology, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX
I integrate biophysics and biochemistry to help address challenges relevant to medicine and biotechnology. I strive to characterize macromolecular complexes including their conformations and interactions that control biological outcomes to mechanistically inform on cancer biology and treatment strategies. My group does this by developing and employing multi-disciplinary biophysical methods with biological collaborations to join structures to biology. Importantly, my projects inform and cross-pollinate one another, so we are more able to successfully and efficiently understand how macromolecular complexes and pathway intersections impact outcomes in cells and humans. Besides hypothesis-driven research, my laboratory develops advanced technology to bridge the gaps from molecular structure to quantitative, predictive cell biology: we do this by creating, testing, and providing technology for insights on dynamic macromolecular conformations and interactions that impact biological outcomes including structure-based design and microbially-inspired solutions to challenges in human health.
I develop funded programs that focus structural biology on medical relevant challenges, such as my Structural Biology of DNA Repair (SBDR) NCI program project. My RO1 lab projects center on cellular stress responses (DNA repair impacting genome integrity and tumorigenesis, reactive oxygen regulators, pathogenesis factors, metalloenzymes, RNA, plus enzyme and inhibitor design). My research and training includes advanced methods development for technologies defining complexes and conformations in solution and at high resolution. I designed, built, and run the synchrotron beamline SIBYLS at the Advanced Light Source (ALS) to integrate small angle x-ray scattering (SAXS) with high-resolution crystal structures for predictive biology - see www.bl1231.als.lbl.gov/. SIBYLS had ~1200 users in the last 5 years and >15 HHMI groups.
Our work on structural biology and SAXS includes introducing new equations for analyzing X-ray scattering data for flexible macromolecules and complexes. We introduced a novel SAXS invariant, the first discovered since the Porod invariant 60 years ago. Furthermore, we develop new metrics for accurate structures, conformations, and assemblies in solution. Our analyses are providing parameters to better assess flexibility, measure intermolecular distances and data to model agreement, reduce false positives, and define resolution.
The SIBYLS facility I built and run (funded by my IDAT and MINOS programs) supports efficient progress in developing and testing the technologies and in characterizing protein interactions, complexes, and conformations in solution and at high resolution. These resources support our growing interests in applying both solution and single crystal methods to structure-based inhibitor design relevant to developing chemical knockouts to complement genetic knockouts, and as eventual therapeutics. The synergy between basic research and technique advancement is allowing us to contribute to basic knowledge and advances relevant to human diseases.
Overall, my group’s research and technology development aims to bridge the gaps from molecular structure to quantitative, mechanistic, and predictive cell biology for organisms. I view this as the age of cell biology with sequencing advances and systems biology opening doors to game changing contributions to fighting human diseases and applying biotechnology. A missing element needed to make current scientific contributions more powerful is a mechanistic understanding at the molecular level that leverages the sequence information and provides a bottom up quantitative and predictive knowledge to objectively link with top down systems biology. I therefore aim to develop tools and technologies to address biology grand challenges, and to connect dynamic structures to biological outcomes. I apply synthetic biology and inhibitor design to learn more about how biological systems work, and to develop useful agents for medicine and nanotechnology. By leveraging my project efforts by strategic collaborations, my goal is to help apply these advances to therapeutics for pathogenesis, degenerative diseases and cancer, and for biotechnology useful for sustainable health in humans.
|1982||Duke University, Durham, NC, USA, PHD, Biochemistry and Structural Biology|
|1974||Trinity College of Arts and Sciences, Duke University, Durham, NC, USA, BA, Zoology and Anthropology|
|1982-1984||Postdoctoral, Structural Biology, The Scripps Research Institute, La Jolla, CA|
Visiting Professor, Division of Life Sciences, The University of California Lawrence Berkeley National Laboratory, Berkeley, CA, 2000 - 2009
Professor, The Scripps Research Institute, La Jolla, CA, 1994 - 2015
Director, Department of Integrated Diffraction Analysis Technologies Program, The University of California Lawrence Berkeley National Laboratory, Berkeley, CA, 2004 - Present
Director, The University of California Lawrence Berkeley National Laboratory, Berkeley, CA, 2001 - Present
Director, The University of California Lawrence Berkeley National Laboratory, Berkeley, CA, 2000 - Present
Director, Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, CA, 1996 - Present
Robert A. Welch, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX, 2015 - Present
- Reyes FE, Schwartz CR, Tainer JA, Rambo RP. Methods for using New Conceptual Tools and Parameters to Assess RNA Structure by Small-Angle X-ray Scattering. In: Methods in Enzymology: Riboswitch Discovery, Structure and Function. 1st. Elsevier, 2014.
- Perry JJP, Shin DS, Tainer JA. Amyotrophic Lateral Sclerosis. In: Diseases of DNA Repair. Springer New York, 9-20, 2010.
- Getzoff ED, Tainer JA. Superoxide Dismutase as a Model Ion Channel. In: Ion Channel Reconstitution. 1. Springer New York, 57-74, 1986.
- Getzoff ED, Hallewell RA, Tainer JA. Structural Implications for Macromolecular Recognition and Redesign. In: Protein Engineering: Applications In Science, Medicine , and Industry. Elsevier, 41-69, 1973.
|Title:||Structural Cell Biology of DNA Repair Machines (SBDR)|
|Title:||MINOS (Macromolecular Insights on Nucleic acids Optimized by Scattering)|
|Title:||Mre11/Rad50/Nbs1 Structural Biology for DNA Damage Responses|
|Title:||Structural Biology of XPB and XPD Helicases|
|Title:||Structural Biochemistry of DNA Dealkylation|
|Title:||IDAT - Integrated diffraction analysis technologies|
|Funding Source:||Dept of Energy|
|Title:||Structural Biochemistry of DNA Base Excision Repair|
|Title:||Fen-1 Complexes and Human Genome Stability|
|Title:||Superoxide Dismutase Structures and Lou Gehrig’s Disease|
|Title:||Type IV Pili & Related Systems|
|Title:||DNA Repair Inhibitors for Cancer Research and Translation|
|Funding Source:||Cancer Prevention & Research Institute of Texas (CPRIT)|
|Title:||Pharmacological Modulation of Poly(ADP-RIBOSE) Metabolism|