The cryo-focused ion beam (FIB) milling technology developed in recent years opens a window for direct visualization of macromolecular interactions inside cell at its physiological state. Combined with cryo-electron tomography (ET) and cryo-correlative light and electron microscopy (CLEM), our group leverage cross-scale technologies to study the structural and functional events of cells in situ, focusing on cancer, a growing global health problem. Since many tumor-related proteins can form micron-scale cellular condensates (via phase separation) and participate in critical events such as signaling and metabolism, our group will study the assembly modes of condensates involved in tumorigenesis and anti-tumor immunity. By further integrating quantitative mass spectrometry (MS), artificial intelligence (AI)-assisted complex structure simulation, and high-resolution structural information, we aim to understand molecular mechanisms for cellular condensate formation. Specific research directions include the molecular architectures of cyclic GMP-AMP synthase condensate, immune synapse, and metabolic condensates directly inside tumor cells, and ultimately the development of new strategies for cancer treatment drug design.

• • 1. Zhang, Xiaojie*; Sridharan, Sindhuja*; Zagoriy, Ievgeniia; Eugster Oegema, Christina; Ching, Cyan; Pflaesterer, Tim; Fung, Herman K.H.; Becher, Isabelle; Poser, Ina; Mu ̈ ller, Christoph W.; Hyman, Anthony A.; Savitski, Mikhail M.^#; Mahamid, Julia^#. Molecular mechanisms of stress-induced reactivation in mumps virus condensates.CELL. Apr 2023.

  • 2. Tollervey, Fergus*; Zhang, Xiaojie; Bose, Mainak; Sachweh, Jenny; Woodruff, Jeffrey B.; Franzmann, Titus M.; Mahamid, Julia^#. Cryo-Electron Tomography of Reconstituted Biomolecular Condensates.METHODS IN MOLECULAR BIOLOGY. Oct 2022.

  • 3. Klumpe, Sven*; Fung, Herman KH*; Goetz, Sara K*; Zagoriy, Ievgeniia; Hampoelz, Bernhard; Zhang, Xiaojie; Erdmann, Philipp S; Baumbach, Janina; Müller, Christoph W; Beck, Martin; Plitzko, Jürgen M^#; Mahamid, Julia^#. A modular platform for automated cryo-FIB workflows.ELIFE. Dec 2021.

  • 4. Jawerth, Louise*; Fischer-Friedrich, Elisabeth; Saha, Suropriya; Wang, Jie; Franzmann, Titus; Zhang, Xiaojie; Sachweh, Jenny; Ruer, Martine; Ijavi, Mahdiye; Saha, Shambaditya; Mahamid, Julia; Hyman, Anthony A.^#; Jülicher, Frank^#. Protein condensates as aging Maxwell fluids.SCIENCE. Dec 2020.

  • 5. Allegretti, Matteo*; Zimmerli, Christian E.*; Rantos, Vasileios; Wilfling, Florian; Ronchi, Paolo; Fung, HermanK.H.; Lee, Chia Wei; Hagen, Wim; Turoňová, Beata; Karius, Kai; Börmel, Mandy; Zhang, Xiaojie; Müller, Christoph W.; Schwab, Yannick; Mahamid, Julia; Pfander, Boris^#; Kosinski, Jan^#; Beck, Martin^#. In-cell architecture of the nuclear pore and snapshots of its turnover.NATURE. Oct 2020.

  • 6. Zhang, Xiaojie*; Mahamid, Julia^#. Addressing the challenge of in situ structural studies of RNP granules in light of emerging opportunities. CURRENT OPINION IN STRUCTURAL BIOLOGY. Jul 2020.

  • 7. Guille ́ n-Boixet, Jordina*; Kopach, Andrii*; Holehouse, Alex S.; Wittmann, Sina; Jahnel, Marcus; Schlu ̈ ßler, Raimund; Kim, Kyoohyun; Trussina, Irmela R.E.A.; Wang, Jie; Mateju, Daniel; Poser, Ina; Maharana, Shovamayee; Ruer-Gruß, Martine; Richter, Doris; Zhang, Xiaojie; Chang, Young-Tae; Guck, Jochen; Honigmann, Alf; Mahamid, Julia; Hyman, Anthony A.; Pappu, Rohit V.; Alberti, Simon^#; Franzmann, Titus M.. RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation.CELL. Apr 2020.

  • 8. Wang, Jie*; Choi, Jeong-Mo; Holehouse, Alex S.; Lee, Hyun O.; Zhang, Xiaojie; Jahnel, Marcus; Maharana, Shovamayee; Lemaitre, Re ́ gis; Pozniakovsky, Andrei; Drechsel, David; Poser, Ina; Pappu, Rohit V.; Alberti, Simon^#; Hyman, Anthony A.^#. A Molecular Grammar Governing the Driving Forces for Phase Separation of Prion-like RNA Binding Proteins.CELL. Jul 2018.

  • 9. Negri, Ana*; Javidnia, Prisca*; Mu, Ran*; Zhang, Xiaojie*; Vendome, Jeremie; Gold, Ben; Roberts, Julia; Barman, Dipti; Ioerger, Thomas; Sacchettini, James C.; Jiang, Xiuju; Burns-Huang, Kristin; Warrier, Thulasi; Ling, Yan; Warren, J. David; Oren, Deena A.; Beuming, Thijs; Wang, Hongyao; Wu, Jie; Li, Haitao; Rhee, Kyu Y.; Nathan, Carl F.; Liu, Gang; Somersan-Karakaya, Selin^#. Identification of a Mycothiol-Dependent Nitroreductase from Mycobacterium tuberculosis.ACS INFECTIOUS DISEASES. Feb 2018.

  • 10. Zhao, Dan*; Zhang, Xiaojie; Guan, Haipeng; Xiong, Xiaozhe; Shi, Xiaomeng; Deng, Haiteng; Li, Haitao^#. The BAH domain of BAHD1 is a histone H3K27me3 reader.PROTEIN & CELL. Mar 2016.

  • 11. Zhang, Xiaojie*; Zhao, Dan; Xiong, Xiaozhe; He, Zhimin; Li, Haitao^#. Multifaceted Histone H3 Methylation and Phosphorylation Readout by the Plant Homeodomain Finger of Human Nuclear Antigen Sp100C.JOURNAL OF BIOLOGICAL CHEMISTRY. Apr 2016.