School of Medicine
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Professor of Photon Science and of Structural Biology
Current Research and Scholarly Interests Ubiquitin signaling: structure, function, and therapeutics
Ubiquitin is a small protein modifier that is ubiquitously produced in the cells and takes part in the regulation of a wide range of cellular activities such as gene transcription and protein turnover. The key to the diversity of the ubiquitin roles in cells is that it is capable of interacting with other cellular proteins either as a single molecule or as different types of chains. Ubiquitin chains are produced through polymerization of ubiquitin molecules via any of their seven internal lysine residues or the N-terminal methionine residue. Covalent interaction of ubiquitin with other proteins is known as ubiquitination which is carried out through an enzymatic cascade composed of the ubiquitin-activating (E1), ubiquitin-conjugating (E2), and ubiquitin ligase (E3) enzymes. The ubiquitin signals are decoded by the ubiquitin-binding domains (UBDs). These domains often specifically recognize and non-covalently bind to the different ubiquitin species, resulting in distinct signaling outcomes.
We apply a combination of the structural (including protein crystallography, small angle x-ray scattering, cryo-electron microscopy (Cryo-EM) etc.), biocomputational and biochemical techniques to study the ubiquitylation and deubiquitination processes, and recognition of the ubiquitin chains by the proteins harboring ubiquitin-binding domains. Current research interests including SARS-COV2 proteases and their interactions with polyubiquitin chains and ubiquitin pathways in host cell responses, with an ultimate goal of providing strategies for effective therapeutics with reduced levels of side effects.
Protein self-assembly processes and applications.
The Surface layers (S-layers) are crystalline protein coats surrounding microbial cells. S-layer proteins (SLPs) regulate their extracellular, self-assembly by crystallizing when exposed to an environmental trigger. We have demonstrated that the Caulobacter crescentus SLP readily crystallizes into sheets both in vivo and in vitro via a calcium-triggered multistep assembly pathway. Observing crystallization using a time course of Cryo-EM imaging has revealed a crystalline intermediate wherein N-terminal nucleation domains exhibit motional dynamics with respect to rigid lattice-forming crystallization domains. Rate enhancement of protein crystallization by a discrete nucleation domain may enable engineering of kinetically controllable self-assembling 2D macromolecular nanomaterials. In particular, this is inspiring designing robust novel platform for nano-scale protein scaffolds for structure-based drug design and nano-bioreactor design for the carbon-cycling enzyme pathway enzymes. Current research focuses on development of nano-scaffolds for high throughput in vitro assays and structure determination of small and flexible proteins and their interaction partners using Cryo-EM, and applying them to cancer and anti-viral therapeutics.
Multiscale imaging and technology developments.
Multimodal, multiscale imaging modalities will be developed and integrated to understand how molecular level events of key enzymes and protein network are connected to cellular and multi-cellular functions through intra-cellular organization and interactions of the key machineries in the cell. Larger scale organization of these proteins will be studied by solution X-ray scattering and Cryo-EM. Their spatio-temporal arrangements in the cell organelles, membranes, and cytosol will be further studied by X-ray fluorescence imaging and correlated with cryoEM and super-resolution optical microscopy. We apply these multiscale integrative imaging approaches to biomedical, and environmental and bioenergy research questions with Stanford, DOE national labs, and other domestic and international collaborators.
Rebecca D. Walker
Clinical Associate Professor, Emergency Medicine
Current Research and Scholarly Interests Interests include international development in emergency care, healthcare disparities, wilderness medicine, human rights, administration
Associate Professor of Pediatrics (Systems Medicine), of Biomedical Data Science and, by courtesy, of Psychiatry and Behavioral Sciences
Current Research and Scholarly Interests Systems biology for design of clinical solutions that detect and treat disease
Associate Professor of Surgery (Pediatric Surgery) at the Lucile Salter Packard Children's Hospital and, by courtesy, of Bioengineering
Current Research and Scholarly Interests Health Technology Innovation
Brian A. Wandell
Isaac and Madeline Stein Family Professor and Professor, by courtesy, of Electrical Engineering, of Ophthalmology and at the Graduate School of Education
Current Research and Scholarly Interests Models and measures of the human visual system. The brain pathways essential for reading development. Diffusion tensor imaging, functional magnetic resonance imaging and computational modeling of visual perception and brain processes.
C. Jason Wang, MD, PhD
Associate Professor of Pediatrics (General Pediatrics) at the Lucile Salter Packard Children's Hospital and of Medicine (PCOR) and, by courtesy, of Epidemiology and Population Health
Bio Dr. Wang is the Director of Center for Policy, Outcomes and Prevention. Prior to coming to Stanford in 2011, he was a faculty member at Boston University Schools of Medicine and Public Health. His other professional experiences include working as a management consultant with McKinsey and Company and serving as the project manager for Taiwan's National Health Insurance Reform Task-force. His current interests include: 1) COVID-19 related policies; 2) developing tools for assessing and improving the value of healthcare; 3) facilitating the use of mobile technology in improving quality of care; 4) supporting competency-based medical education curriculum, and 5) engaging in healthcare delivery and payment reforms.
Postdoctoral Research Fellow, Radiation Biology
Bio Jinglong was trained in a single-molecule lab in Institute Jacques Monod and École Normale Supérieure Paris and obtained his PhD degree from University of Paris in 2019, France. He dissected the molecular machinery of human and bacterial Non-homologous end joining, and interrogated the mechanism of SpCas9 plasticity on targeting DNA with deviant PAMs using single-molecule nanomanipulation tools. Jinglong joined the Frock lab in Jan 2020, and he is working on DSB-related chromosome topological changes and genomic interactions.
Kevin Wang, MD, PhD
Assistant Professor of Dermatology
Current Research and Scholarly Interests The Wang lab takes an interdisciplinary approach to studying fundamental mechanisms controlling gene expression in mammalian cells, and how epigenetic mechanisms such as DNA methylation, chromatin modifications, and RNA influence chromatin dynamics to affect gene regulation.
Clinical Associate Professor, Pediatrics
Current Research and Scholarly Interests Evaluation and management of the febrile young infant and infections in hospitalized children (eg, UTIs, CNS infections, pneumonia); promotion of appropriate antibiotic use.