Gabriel Lander, PhD
Professor
Department of Integrative Structural and Computational Biology
Research Focus
We work to develop methodologies that expand the limits of achievable resolution through optimized specimen preparation and cryo-EM data collection strategies, as well as novel image processing algorithms. Combining these cryo-EM techniques with biochemical, biophysical, and cellular studies, we aim to unravel the intricate molecular dynamics governing cellular homeostasis and stress responses. Our work primarily focuses on the mechanisms that underlie protein degradation, which is a fundamental process that plays a paramount role in upholding cellular equilibrium and function. Many of these processes are orchestrated by large-scale conformational rearrangements, protein oligomerization, or motions of molecular motors, which together control the selection, recruitment, unfolding, and elimination of targeted proteins. By complementing cryo-EM structure determination with complementary computational and experimental studies, we describe the intricate connections between molecular mechanisms and human diseases. We also explore the role of small molecules in modulating these intricate systems with potential therapeutic effects. By understanding how these molecules impact processes such as protein ubiquitination and degradation, we aim to unlock novel avenues for targeted interventions that could have far-reaching implications disease treatment.
Select Publications
-
Yang, Jie; Baron, Kelsey R.; Pride, Dani E.; Schneemann, Anette; Guo, Xiaoyan; Chen, Wenqian; Song, Albert S.; Aviles, Giovanni; Kampmann, Martin; Luke Wiseman, R; Lander, Gabriel C. DELE1 oligomerization promotes integrated stress response activation. 2023.
-
Watson, Edmond R.; Novick, Scott; Matyskiela, Mary E.; Chamberlain, Philip P P.; H de la Peña, Andres; Zhu, Jinyi; Tran, Eileen; Griffin, Pat R.; Wertz, Ingrid E.; Lander, Gabriel C. Molecular glue CELMoD compounds are regulators of cereblon conformation. 2022, 378, 549-553.
-
Swan, Jeffrey A.; Sandate, Colby R.; Chavan, Archana G.; Freeberg, Alfred M.; Etwaru, Diana; Ernst, Dustin C.; Palacios, Joseph G.; Golden, Susan S S.; LiWang, Andy; Lander, Gabriel C.; Partch, Carrie L. Coupling of distant ATPase domains in the circadian clock protein KaiC. 2022, 29, 759-766.
-
Shin, Mia; Watson, Edmond R.; Song, Albert S.; Mindrebo, Jeffrey T.; Novick, Scott J.; Griffin, Pat R.; Wiseman, R L.; Lander, Gabriel C. Structures of the human LONP1 protease reveal regulatory steps involved in protease activation. 2021, 12, 3239.
-
de la Pena, A. H.; Goodall, E. A.; Gates, S. N.; Lander, Gabriel C.; Martin, A. Substrate-engaged 26S proteasome structures reveal mechanisms for ATP-hydrolysis-driven translocation. Science 2018, 362.
View -
Lander, Gabriel C.; Lander, Gabriel C.; Grotjahn, Danielle A.; Chowdhury, Saikat; Basanta, Benjamin A guided approach for subtomogram averaging of challenging macromolecular assemblies.. Journal of structural biology: X 2020, 4, 100041.
View -
Puchades Garcia, Cristina; Rampello, A. J.; Shin, Mia; Giuliano, C. J.; Wiseman, Rockland L.; Glynn, S. E.; Lander, Gabriel C. Structure of the mitochondrial inner membrane AAA+ protease YME1 gives insight into substrate processing. Science 2017, 358.
View
