School of Medicine
Showing 11-18 of 18 Results
David B. McKay
Professor of Structural Biology, Emeritus
Current Research and Scholarly InterestsThree-dimensional structure determination and biophysical studies of macromolecules.
Professor of Structural Biology and of Microbiology and Immunology
Current Research and Scholarly InterestsThe Parham laboratory investigates the biology, genetics, and evolution of MHC class I molecules and NK cell receptors.
Joseph (Jody) Puglisi
Jauch Professor and Professor of Structural Biology
Current Research and Scholarly InterestsThe Puglisi group investigates the role of RNA in cellular processes and disease. We investigate dynamics using single-molecule approaches. Our goal is a unified picture of structure, dynamics and function. We are currently focused on the mechanism and regulation of translation, and the role of RNA in viral infections. A long-term goal is to target processes involving RNA with novel therapeutic strategies.
Naima G. Sharaf
Assistant Professor of Biology and, by courtesy, of Structural Biology
BioNaima Sharaf got her undergraduate degree in Chemistry at the University of North Carolina-Chapel Hill. She carried out her Ph.D. studies at the University of Pittsburgh in the lab of Dr. Angela Gronenborn where she used fluorine solution NMR to understand inhibitor-induced conformational changes with HIV-1 reverse transcriptase. To expand her structural biology skill set, she undertook postdoctoral training at Caltech in the lab of Dr. Doug Rees where she characterized the structure and function of the Neisseria meningitides methionine ABC transport system using x-ray crystallography and single-particle cryo-EM. This research sparked Dr. Sharaf's current interest in lipoproteins, particularly their roles in bacterial physiology and potential in vaccine design. Research in the Sharaf Lab bridges biochemistry, biology, microbiology, and immunology to translate lipoprotein research into therapeutics.
Professor of Molecular and Cellular Physiology, of Structural Biology and of Photon Science
BioThe Skiniotis laboratory seeks to resolve structural and mechanistic questions underlying biological processes that are central to cellular physiology. Our investigations employ primarily cryo-electron microscopy (cryoEM) and 3D reconstruction techniques complemented by biochemistry, biophysics and simulation methods to obtain a dynamic view into the macromolecular complexes carrying out these processes. The main theme in the lab is the structural biology of cell surface receptors that mediate intracellular signaling and communication. Our current main focus is the exploration of the mechanisms responsible for transmembrane signal instigation in cytokine receptors and G protein coupled receptor (GPCR) complexes.
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.
William M. Hume Professor in the School of Medicine, Professor of Structural Biology, of Molecular and Cellular Physiology and of Photon ScienceOn Partial Leave from 09/01/2021 To 08/31/2022
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.