School of Medicine
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Soichi Wakatsuki
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. -
Claire E Wakefield
Professor of Pediatrics (Quality of Life and Palliative Care)
BioI am a medical psychologist and researcher dedicated to improving quality of life for children who are very sick, as well as their families. My work focuses on developing evidence-based psychosocial interventions that support families facing childhood cancer and other serious conditions. My research spans pediatric palliative care, precision medicine, and global health, and is grounded in a deep commitment to compassionate, patient-centered care.
I serve as Continental President of SIOP Oceania and as a Director on the Board of the International Society of Pediatric Oncology (SIOP), advocating for children with cancer across 14 countries. I also advise the World Health Organization on global childhood cancer initiatives and am a proud member of the Presidential Task Force on Advocacy for the Society of Pediatric Psychology. I am passionate about building national and global capacity in pediatric palliative care and ensuring that every child and family receives not only the best medical treatment, but also the emotional and psychological support they need. -
Diane Elizabeth Wakeham
Clinical Research Coordinator Associate, Psych/General Psychiatry and Psychology (Adult)
Current Role at StanfordClinical Research Coordinator Associate, INSPIRE Clinic, Psychiatry and Behavioral Sciences
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Heather Wakelee
Winston Chen and Phyllis Huang Professor
Current Research and Scholarly InterestsDr. Wakelee's research is focused on clinical trials and translational efforts in patients with lung cancer and other thoracic malignancies such as thymoma and thymic carcinoma. Other interests include translation projects in thoracic malignancies and collaborations with population scientists regarding lung cancer questions.
