School of Medicine
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Professor of Photon Science and of Structural Biology
Current Research and Scholarly InterestsUbiquitin 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 InterestsInterests include international development in emergency care, healthcare disparities, wilderness medicine, human rights, administration
Professor of Pediatrics (Systems Medicine), of Biomedical Data Science and, by courtesy, of Psychiatry and Behavioral Sciences
Current Research and Scholarly InterestsSystems biology for design of clinical solutions that detect and treat disease
Associate Professor of Surgery (Pediatric Surgery) and, by courtesy, of BioengineeringOn Partial Leave from 07/01/2023 To 06/30/2024
Current Research and Scholarly InterestsHealth 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 InterestsModels 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. Image systems simulations of optics and sensors and image processing. Data and computation management for reproducible research.
Postdoctoral Scholar, Stem Cell Transplantation
BioMy academic training and research experience have equipped me with multidisciplinary skills and knowledge of molecular biology and immunology.
I led two projects when I was an undergraduate, in which I got primary academic learning. My team member and I investigated the bacteria content in drinking water from two types of machines that are commonly used in colleges under the guidance of our experimental microbiology teacher Zhihong Zhong. Secondly, we produced a hybridoma cell line secreting monoclonal antibody against the core antigen of the hepatitis C virus (HCV) to develop an ELISA kit for the detection of HCV under the guidance of Dr. Rushi Liu and Minjing Liao.
Thereafter, as a Ph. D. candidate at Xiaoming Feng’s lab, my research primarily focused on understanding the biology of regulatory T cells (Treg) and CD11c+ myeloid cells using cutting-edge single-cell sequencing and conditional knockout mice under healthy and disease conditions. We first revealed the heterogeneity and bifurcated differentiation pathway of human Tregs from normal donors and transplanted patients at the single-cell transcriptome level. A subsequent first and corresponding author publication identified a key innate responsive protein in CD11c+ alveolar macrophages, NRP2, that protects mice from lung injury via promoting the phagocytosis of neutrophils. I also participated in two projects regarding the role of a serine/threonine kinase, LKB1, in mice CD11c+ dendritic cells from lymphoid tissues and adipose tissue with diet-induced obesity. These academic experiences guided me into a strong passion and independent capacities for biomedical studies.
For my postdoctoral training, I will focus on developing Treg therapies and genetic stem cell therapy to cure patients with IPEX syndrome (a severe autoimmune disease) at preclinical and clinical stages, and other immune disorders. My sponsor Dr. Rosa Bacchetta is a well-known leader in treating IPEX patients and developing Treg therapies. My co-mentor Dr. Maria Grazia Roncarolo is a well-recognized pediatric immunologist and also one of the pioneers in the stem cell and gene therapy field, who discovered the type 1 regulatory T cells or Tr1 cells and translate the scientific discoveries into novel Treg therapies. Both of them have an excellent record of training postdoctoral fellows. The proposed projects will provide me with great opportunities in cutting-edge technology and translational research and outline a set of career development including grant writing, public presentation, and lab management, which will enhance my ability to become an independent investigator and help me to reach my goal of developing efficient and safe Treg therapies for a wide range of immune disorders and associated human diseases.
C. Jason Wang, MD, PhD
Bowei Lee Professor and Professor of Pediatrics (General Pediatrics) and of Health Policy
BioDr. 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 Scholar, Radiation Biology
BioDr. Wang was trained at the Jacques Monod Institute and École Normale Supérieure in Paris, France under the mentorship of Dr. Terence Strick. and obtained his Ph.D. degree from the University of Paris in 2019. He dissected the molecular machinery of human and bacterial NHEJ, and interrogated the mechanism of SpCas9 tolerance to non-specific substrate using single-molecule nanomanipulation tools.
Jinglong’s research in the Frock Lab focuses on DSB-related chromosome topological changes and genomic interactions.
Kevin Wang, MD, PhD
Assistant Professor of Dermatology
Current Research and Scholarly InterestsThe 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.