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James H. Clark Professor in the School of Engineering and Professor of Chemical Engineering and of BioengineeringOn Leave from 10/01/2022 To 06/30/2023
Current Research and Scholarly InterestsProgram Overview
The world we enjoy, including the oxygen we breathe, has been beneficially created by biological systems. Consequently, we believe that innovative biotechnologies can also serve to help correct a natural world that non-natural technologies have pushed out of balance. We must work together to provide a sustainable world system capable of equitably improving the lives of over 10 billion people.
Toward that objective, our program focuses on human health as well as planet health. To address particularly difficult challenges, we seek to synergistically combine: 1) the design and evolution of complex protein-based nanoparticles and enzymatic systems with 2) innovative, uniquely capable cell-free production technologies.
To advance human health we focus on: a) achieving the 120 year-old dream of producing “magic bullets”; smart nanoparticles that deliver therapeutics or genetic therapies only to specific cells in our bodies; b) precisely designing and efficiently producing vaccines that mimic viruses to stimulate safe and protective immune responses; and c) providing a rapid point-of-care liquid biopsy that will count and harvest circulating tumor cells.
To address planet health we are pursuing biotechnologies to: a) inexpensively use atmospheric CO2 to produce commodity biochemicals as the basis for a new carbon negative chemical industry, and b) mitigate the intermittency challenges of photovoltaic and wind produced electricity by producing hydrogen either from biomass sugars or directly from sunlight.
More than 25 years ago, Professor Swartz began his pioneering work to develop cell-free biotechnologies. The new ability to precisely focus biological systems toward efficiently addressing new, “non-natural” objectives has proven tremendously useful as we seek to address the crucial and very difficult challenges listed above. Another critical feature of the program is the courage (or naivete) to approach important objectives that require the development and integration of several necessary-but- not-sufficient technology advances.
Associate Professor of Mechanical Engineering, Senior Fellow at the Woods Institute for the Environment and Professor, by courtesy, of Radiology (Precision Health and Integrated Diagnostics)
Current Research and Scholarly InterestsThe long-term goal of Dr. Tang's research program is to harness mass transport in microfluidic systems to accelerate precision medicine and material design for a future with better health and environmental sustainability.
Current research areas include: (I) Physics of droplets in microfluidic systems, (II) Interfacial mass transport and self-assembly, and (III) Applications in food allergy, single-cell wound repair, and the bottom-up construction of synthetic cell and tissues in close collaboration with clinicians and biochemists at the Stanford School of Medicine, UCSF, and University of Michigan.
For details see https://web.stanford.edu/group/tanglab/
Hawa Racine Thiam
Assistant Professor of Bioengineering and of Microbiology and Immunology
Current Research and Scholarly InterestsCellular Biophysical Mechanisms of Innate Immune Cells Functions
Professor of Genetics, of Biology and, by courtesy, of Chemistry
Current Research and Scholarly InterestsWe develop chemogenetic and optogenetic technologies for probing and manipulating protein networks, cellular RNA, and the function of mitochondria and the mammalian brain. Our technologies draw from enzyme engineering, directed evolution, chemical biology, organic synthesis, high-resolution microscopy, genetics, and computational analysis.
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.
Taia T. Wang, MD, PhD, MSCI
Assistant Professor of Medicine (Infectious Diseases) and of Microbiology and Immunology
Current Research and Scholarly InterestsLaboratory of Mechanisms in Human Immunity and Disease Pathogenesis
Studies in our lab are aimed at defining mechanisms in human immunity and disease. We are particularly interested the hypothesis that diversity in antibody-based signaling that arises from diversity in IgG antibodies and their receptors, is a central driver of heterogeneity in human immune functioning and susceptibility to infectious diseases. We are studying how the Fc domain repertoire of an individual impacts the quality of effector cell responses that can be recruited during immune activation and how selectivity of effector responses contributes to immunity and disease.
SARS-CoV-2, dengue viruses, influenza viruses, disease pathogenesis, influenza vaccines
Current clinical studies:
An Open Label Study of IgG Fc Glycan Composition in Human Immunity
Principal Investigator: Taia T. Wang, MD, PhD
Robert Eckles Swain Professor of Chemistry and Professor, by courtesy, of Chemical Engineering
BioRobert Eckles Swain Professor in Chemistry Robert Waymouth investigates new catalytic strategies to create useful new molecules, including bioactive polymers, synthetic fuels, and sustainable plastics. In one such breakthrough, Professor Waymouth and Professor Wender developed a new class of gene delivery agents.
Born in 1960 in Warner Robins, Georgia, Robert Waymouth studied chemistry and mathematics at Washington and Lee University in Lexington, Virginia (B.S. and B.A., respectively, both summa cum laude, 1982). He developed an interest in synthetic and mechanistic organometallic chemistry during his doctoral studies in chemistry at the California Institute of Technology under Professor R.H. Grubbs (Ph.D., 1987). His postdoctoral research with Professor Piero Pino at the Institut fur Polymere, ETH Zurich, Switzerland, focused on catalytic hydrogenation with chiral metallocene catalysts. He joined the Stanford University faculty as assistant professor in 1988, becoming full professor in 1997 and in 2000 the Robert Eckles Swain Professor of Chemistry.
Today, the Waymouth Group applies mechanistic principles to develop new concepts in catalysis, with particular focus on the development of organometallic and organic catalysts for the synthesis of complex macromolecular architectures. In organometallic catalysis, the group devised a highly selective alcohol oxidation catalyst that selectively oxidizes unprotected polyols and carbohydrates to alpha-hyroxyketones. In collaboration with Dr. James Hedrick of IBM, we have developed a platform of highly active organic catalysts and continuous flow reactors that provide access to polymer architectures that are difficult to access by conventional approaches.
The Waymouth group has devised selective organocatalytic strategies for the synthesis of functional degradable polymers and oligomers that function as "molecular transporters" to deliver genes, drugs and probes into cells and live animals. These advances led to the joint discovery with the Wender group of a general, safe, and remarkably effective concept for RNA delivery based on a new class of synthetic cationic materials, Charge-Altering Releasable Transporters (CARTs). This technology has been shown to be effective for mRNA based cancer vaccines.
William M. Hume Professor in the School of Medicine, Professor of Structural Biology, of Molecular and Cellular Physiology and of Photon Science
Current Research and Scholarly InterestsOur laboratory studies molecular interactions that underlie the establishment and maintenance of cell and tissue structure. Our principal areas of interest are the architecture and dynamics of intercellular adhesion junctions, signaling pathways that govern cell fate determination, and determinants of cell polarity. Our overall approach is to reconstitute macromolecular assemblies with purified components in order to analyze them using biochemical, biophysical and structural methods.
Francis W. Bergstrom Professor and Professor, by courtesy, of Chemical and Systems Biology
Current Research and Scholarly InterestsMolecular imaging, therapeutics, drug delivery, drug mode of action, synthesis
Albert Y. Wu, MD, PhD, FACS
Assistant Professor of Ophthalmology
Current Research and Scholarly InterestsMy translational research focuses on using autologous stem cells to recreate a patient’s ocular tissues for potential transplantation. We are generating tissue from induced pluripotent stem cells to treat limbal stem cell deficiency in patients who are bilaterally blind. By applying my background in molecular and cellular biology, stem cell biology, oculoplastic surgery, I hope to make regenerative medicine a reality for those suffering from orbital and ocular disease.
Joseph C. Wu, MD, PhD
Director, Stanford Cardiovascular Institute, Simon H. Stertzer, MD, Professor and Professor of Radiology
Current Research and Scholarly InterestsDrug discovery, drug screening, and disease modeling using iPSC.
Tony Wyss-Coray, PhD
D. H. Chen Professor II
Current Research and Scholarly InterestsUse of genetic and molecular tools to dissect immune and inflammatory pathways in Alzheimer's and neurodegeneration.
Priscilla Li-ning Yang
Professor of Microbiology and Immunology
Current Research and Scholarly InterestsWe apply chemical biology approaches to study fundamental virological processes and to develop antivirals with novel mechanisms of action.
J. Bradley Zuchero
Assistant Professor of Neurosurgery
Current Research and Scholarly InterestsGlia are a frontier of neuroscience, and overwhelming evidence from the last decade shows that they are essential regulators of all aspects of the nervous system. The Zuchero Lab aims to uncover how glial cells regulate neural development and how their dysfunction contributes to diseases like multiple sclerosis (MS) and in injuries like stroke.
Although glia represent more than half of the cells in the human brain, fundamental questions remain to be answered. How do glia develop their highly specialized morphologies and interact with neurons to powerfully control form and function of the nervous system? How is this disrupted in neurodegenerative diseases and after injury? By bringing cutting-edge cell biology techniques to the study of glia, we aim to uncover how glia help sculpt and regulate the nervous system and test their potential as novel, untapped therapeutic targets for disease and injury.
We are particularly interested in myelin, the insulating sheath around neuronal axons that is lost in diseases like MS. How do oligodendrocytes- the glial cell that produces myelin in the central nervous system- form and remodel myelin, and why do they fail to regenerate myelin in disease? Our current projects aim to use cell biology and neuroscience approaches to answer these fundamental questions. Ultimately we hope our work will lead to much-needed therapies to promote remyelination in patients.