基本信息
浏览量:9
职业迁徙
个人简介
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 64 篇作者统计合作学者相似作者
按年份排序按引用量排序主题筛选期刊级别筛选合作者筛选合作机构筛选
时间
引用量
主题
期刊级别
合作者
合作机构
Cancer Researchno. 6_Supplement (2024): 6404-6404
Journal of Clinical Oncologyno. 16_suppl (2024)
Susan Tsutakawa, Alyssa Easton, Nagababu Chinnam,Runze Shen,Greg Hura,Andriy Kryshtafovych,Andrew Lovering, Mark Vanraaj,Krzysztof Fidelis,John Tainer
PROTEIN SCIENCEno. 12 (2023)
引用0浏览0引用
0
0
Journal of biological chemistry/The Journal of biological chemistryno. 3 (2023): 103366-103366
Methods in Enzymology (2023): XV-XIX
引用0浏览0引用
0
0
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature (2018)
加载更多
作者统计
#Papers: 64
#Citation: 1248
H-Index: 14
G-Index: 35
Sociability: 6
Diversity: 1
Activity: 0
合作学者
合作机构
D-Core
- 合作者
- 学生
- 导师
数据免责声明
页面数据均来自互联网公开来源、合作出版商和通过AI技术自动分析结果,我们不对页面数据的有效性、准确性、正确性、可靠性、完整性和及时性做出任何承诺和保证。若有疑问,可以通过电子邮件方式联系我们:report@aminer.cn