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职业迁徙
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Research Interests
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.
研究兴趣
论文共 263 篇作者统计合作学者相似作者
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Ryan Woltz,Brandon Schweibenz,Susan E Tsutakawa,Chen Zhao,LiChung Ma, Ben Shurina,Gregory L Hura, Rachael John,Sergey Vorobiev, Gvt Swapna,Mihai Solotchi,John A Tainer,
bioRxiv : the preprint server for biology (2024)
Cancer Researchno. 6_Supplement (2024): 6404-6404
Ryan Woltz,Brandon Schweibenz,Susan E. Tsutakawa,Chen Zhao,Li-Chung Ma,Ben Shurina,Greg L Hura, Rachael John,Sergey Vorobiev, Swapna Gurla,Mihai Solotchi,John A. Tainer,
bioRxiv (Cold Spring Harbor Laboratory) (2024)
Zu Ye, Shengfeng Xu,Yin Shi,Xueqian Cheng,Yuan Zhang,Sunetra Roy,Sarita Namjoshi, Michael A. Longo,Todd M. Link,Katharina Schlacher,Guang Peng,Dihua Yu,
JOURNAL OF BIOLOGICAL CHEMISTRYno. 3 (2023): S169-S169
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Susan Tsutakawa, Alyssa Easton, Nagababu Chinnam,Runze Shen,Greg Hura,Andriy Kryshtafovych,Andrew Lovering, Mark Vanraaj,Krzysztof Fidelis,John Tainer
PROTEIN SCIENCEno. 12 (2023)
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Molecular cellno. 13 (2023): 2258-2275.e11
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Journal of Biological Chemistryno. 3 (2023): 103366-S169
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Nucleic acids researchno. 3 (2023): 1019-1033
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