The Biochemistry, Molecular, Cellular and Developmental Biology (BMCDB) Graduate Group faculty have wide-ranging research interests. These interests fall into 15 specializations. There are over 100 faculty members in the BMCDB Graduate Group from more than 18 departments, colleges and schools on campus.
A list of all faculty affiliated with BMCDB Graduate Group is on this Web page, or you may view a list of faculty by specialization and research interests through the drop-down menu.
Chair of BMCDB: Mitch Singer
Click on a faculty member's name to view his or her full profile.
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jawdat@ucdavis.edu
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Molecular & Cellular Biology
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The Structure and Mechanisms of Microtubule Regulatory Proteins in Assembly and Disassembly of tubulin dimers
Microtubules are dynamic polymers that are critical for many physical transformations that cells undergo in order to divide, develop, or generate motility. Microtubules assemble from basic building blocks, called alpha beta (αβ) tubulin dimers, which polymerize head-to-tail to form protofilaments, using the energy of Guanosine 3,5 Triphosphate (GTP) binding and hydrolysis; These tubulin protofilaments associate laterally enclosing a tube-like structure-- a microtubule. Tubulin polymerization activates GTP hydrolysis only within the microtubule wall and leads to stochastic events called catastrophes, in which protofilaments peel ane curl to disassemble the microtubule structure. The dynamics of tubulin heterodimer assembly and disassembly into microtubules occurs at the ends of microtubules, and are highly regulated by conserved types of proteins that are found in all organisms. These proteins, in effect, act as MT “Polymerases” and “Depolymerases” accelerating the slow processes of polymerization and depolymerization that tubulin dimers can carry-out alone. The laboratory is focused on deciphering the mechanisms of these microtubule regulatory proteins and how they cooperate to regulate microtubule dynamics in highly synchronized cellular phenomena like cell division and development. The physical scale of microtubule dynamics can be studied multiple approaches that span a great resolution scale span from micro-meters to the sub-nanometer scale. The Laboratory combines biochemistry, structural biology approaches such as electron microscopy and X-ray crystallography, with high resolution single molecule total internal reflection microscopy to study the mechanisms of Microtubule Polymerases and Depolymerases at multiple levels of spatial and temporal resolution.
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pbarmstrong@ucdavis.edu
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Molecular & Cellular Biology
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Tissue morphodynamics
Role of cell-cell and cell-extracellular matrix adhesion in the determination of tissue structure. Cell adhesion to the extracellular matrix: regulation of cell motility and proliferation. Mechanisms of intercellular invasion. Regulation of embryonic morphogenesis. Mode of action of peptide growth factors.
Comparative immunology
Comparative biology of evolutionarily conserved effectors of the innate immune system: a2-macroglobulin & C-reactive protein. Role of the blood clotting system in immunity. Lipopolysaccharide/endotoxin: immune defense against endotoxemia, phylogenetic distribution of lipopolysaccharide.
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satsumi@ucdavis.edu
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Chemistry
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Synthetic biology for biofuel production
An increased understanding of system properties underlying cellular networks enables us to construct novel systems by assembling the components and the control systems into new combinations. We are applying this approach to the field of metabolic engineering, which strives for the optimization of desired properties and functions, such as the production of valuable biochemicals. The production of valuable chemicals from microorganisms suites to solve some significant challenges, such as converting renewable feedstocks into energy-rich biofuels. Currently, our main focus is developing synthetic organisms capable of converting CO2 directly to biofuels.
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epbaldwin@ucdavis.edu
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Molecular & Cellular Biology
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Structural Biochemistry, Enzymology and Protein Engineering of Protein-nucleic acid Interactions
X-ray crystallography, protein and DNA structure and function, and protein engineering, focusing on enzymology and molecular recognition. Model systems include DNA and nucleotide binding proteins and enzymes.
RESEARCH TARGETS:
My lab uses X-ray crystallography, biochemistry and molecular genetics to dissect and engineer mechanisms of DNA binding proteins and enzymes involved in nucleic acid metabolism. A recent primary focus is the DNA specificity and function of sequence-progammable TALE DNA binding proteins. A second focus is the mechanism and regulation of Cytidine Triphosphate Synthetase, the ultimate enzyme for pyrimidine biosynthesis, and a target for anti-cancer and anti-parasitic drugs.
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pabeal@ucdavis.edu
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Chemistry
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kabeck@ucdavis.edu
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Cell Biology & Human Anatomy
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abbennett@ucdavis.edu
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Plant Science
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dmbers@ucdavis.edu
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Pharmacology - Medicine
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Cardaic Physiology
Much of his scientific work has focused on Ca regulation in the heart, but this includes fundamental quantitative mechanistic characterization of ion transporters and channels, electrophysiology, excitation-contraction coupling, myofilament activation, mitochondrial Ca/ energetics, cellular kinase signaling, systolic dysfunction and arrhythmogenesis (e.g. in hypertrophy and heart failure), always with an eye toward both integrative aspects of cardiac function/ clinical relevance and identification of novel therapeutic targets in cardiovascular disease. The experimental approaches used are multidisciplinary including physiology, biophysics, molecular biology, biochemistry, real-time dynamic confocal & TIRF imaging and computational modeling.
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CLBevins@ucdavis.edu
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Microbiology - Medicine
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Innate Immunity, Host Microbe Interaction, Defensins
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lfbisson@ucdavis.edu
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Viticulture & Enology
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eblumwald@ucdavis.edu
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Plant Science
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lnborodinsky@ucdavis.edu
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Physiology and Membrane Biology
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adborowsky@ucdavis.edu
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Pathology - Medicine
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abbritt@ucdavis.edu
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Plant Biology
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Genetics of DNA repair and mutagenesis in the higher plant Arabidopsis. How plants repair and/or tolerate DNA damage generated by chemicals, UV light, and gamma radiation. Processes of genetic recombination, in meiotic and mitotic cells. Transcriptional regulation of damage response.
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nlbrown@ucdavis.edu
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Cell Biol & Human Anatomy
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Mammalian Developmental Genetics
My research group aims to understand the molecular mechanisms regulating the formation of the mammalian lens and retina. We are investigating the genetic pathways underlying lens and retinal tissue formation during embryogenesis. This research will contribute to a better understanding of congenital eye diseases and ultimately inform therapies that can correct vision loss. Currently we are focused on understanding: 1) how lens progenitor cells stop dividing and turn into fiber cells, and 2) how retinal progenitor cells choose to become one type of neuron, although multiple fates are available to them.
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nbrowning@ucdavis.edu
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Molecular & Cellular Biology
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smburgess@ucdavis.edu
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Molecular & Cellular Biology
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Meiotic chromosome dynamics
Work in my laboratory explores the dynamic chromosome events that occur during the process of meiosis and how these processes are integrated to achieve accurate chromosome segregation. Chromosome missegregation is one of the leading causes of birth defects in humans. We combine the use of a wide array of tools, including genetics, molecular biology, biochemistry and live-cell imaging using budding yeast Saccharomyces cerevisiae as a model system.
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meburns@ucdavis.edu
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Ophthalmology - Medicine
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The first steps in vision begin in the rods and cones of the retina, which use a G-protein signaling cascade to transduce absorbed photons into electrical signals. Our lab examines the biochemical rates and biophysical properties of signaling in rods, as well as the consequences of defective signaling on visual performance. We are also trying to understand how defective signaling can lead to photoreceptor degeneration, which is one of the leading causes of congenital blindness in humans.
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jcallis@ucdavis.edu
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Molecular & Cellular Biology
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The ubiquitin pathway is a protein modification pathway, whereby the protein ubiquitin is covalently attached to other proteins. This alters the longevity, activity or localization of the ubiquitinated protein. We are interested in understanding the specificity and regulation of the ubiquitin pathway. We try to understand how proteins are recruited to the ubiquitinating enzymes. There are are large number of ubiquitinating enzymes whose functions are not known. We are taking a reverse genetics approach to understand the function of RING E3 ligases which interact with substrate proteins and catalyze ubiquitin transfer. We also study a ubiquitin-like protein, RUB, for Related to ubiquitin, and are trying to identify RUB-modified proteins in plants. We use a variety of techniques- biochemistry, molecular biology and genetics.
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klcarraway@ucdavis.edu
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Biochemistry and Molecular Medicine
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Cancer biology and therapeutics
Research in the lab centers on elucidating the cellular and molecular mechanisms underlying tumor formation and progression, and developing strategies and agents that could interfere with these processes. We are specifically interested in post-transcriptional regulatory pathways, such as cellular trafficking and degradation of growth factor receptors and disruption of cell polarity pathways, that contribute to cancer malignancy. We use biochemical and cell biological methods to elucidate these pathways in cultured tumor cells, genetically engineered mice to characterize dysregulated tumorigenic pathways in vivo, and drug development and characterization methods to inhibit these pathways.
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flchedin@ucdavis.edu
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Molecular & Cellular Biology
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Mammalian epigenetics
I am interested in elucidating the molecular mechanisms that are responsible for setting up cytosine DNA methylation patterns in the human genome. How these mechanisms go awry in disease conditions, in particular in auto-immune disorders and cancer, is also of direct relevance to my work. To investigate these question, my group makes use of (epi)genomics tools, mammalian cell culture assays and biochemistry.
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hwzchen@ucdavis.edu
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Biochemistry and Molecular Medicine
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Chromatin/epigenetic regulators in hormone signaling and in cancer
Our research includes identification and elucidation of key epigenetic regulators that function in cancer and in hormone signaling. Steroid hormone signaling plays crucial roles in control of cell growth and differentiation through the nuclear hormone receptors such as estrogen receptors and androgen receptor and their associated coregulators. We focus on understanding how some of the coregulators (e.g. ANCCA, histone methylases and demethylases) mediate gene expression control and hormone-dependent growth and differentiation via chromatin histone modifications and remodeling and how their aberrant functions contribute to tumorigenesis. Our objectives are to identify the key chromatin regulators that play important functions in the nuclear receptor-dependent hormone signaling in prostate and mammary gland, to identify the important epigenetic regulators in the initiation and/or progression of breast cancer and prostate cancer, to elucidate the molecular mechanisms of the epigenetic regulators, and to demonstrate the potential of the epigenetic regulators as biomarkers and therapeutic targets.We employ a number of molecular and cell biology approaches, including gene expression microarray, chromatin immunoprecipitation (ChIP) or ChIP-seq, for analysis of chromatin modification and remodeling, coregulator assembly and gene expression, as well as genetic approach (e.g. mouse ko models) for determining the physiological and pathological functions of the chromatin regulators.
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tycchen@ucdavis.edu
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Neurology - Medicine
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Structures, functions and physiological roles of ion channels and transporters.
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xbchen@ucdavis.edu
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VM Surgical & Radiological Sci
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hjcheng (at) ucdavis (dot) edu
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Neurobiology, Physiology and Behavior
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My lab studies the molecular and cellular mechanisms of axon guidance. We have used two model organisms, mouse and C. elegans, to study how molecules in the environment guide axons during embryonic development and how these environmental cues are interpreted inside the growing axon. Recently, we have also tried to address whether abnormalities in axon pruning can lead to developmental neuropsychiatric disorders such as schizophrenia and autism.
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jcchiu@ucdavis.edu
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Entomology
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Molecular Genetics of Animal Behavior and Physiology; Circadian Rhythms; Posttranslational modifications of clock proteins
Research in my laboratory focuses on the regulation of circadian clock and its control over organismal physiology. Circadian clocks regulate molecular oscillations that manifest into physiological and behavioral rhythms. The self-sustained molecular oscillator can be synchronized to daily and seasonal environmental changes, thus allowing organisms to perform necessary tasks at biologically advantageous times of day. Besides being indispensable for the control of daily activities in animals, such as the sleep-wake cycle, locomotor activity, hormone circulation and food intake, defects in circadian rhythms and clock genes have also been implicated in a wide range of human disorders, including chronic sleep orders, various forms of depression, metabolic syndromes, as well as susceptibility to cancer and drug and alcohol addiction.
Although circadian clock genes are not highly conserved across kingdoms (plant, animal, fungi, and bacteria), the regulation of circadian oscillators in all organisms studied to date appears to be variations on the same theme. In general, circadian pacemakers are comprised of a set of species and tissue-specific clock genes that are cell-autonomous and autoregulatory through a series of interconnected transcriptional-translational feedback loops. The circadian oscillator is capable of receiving input signals from external time cues, thereby synchronizing its activity to the environment; and can control cell and organismal physiology by regulating the rhythmic expression of downstream effectors in cell and tissue-specific manners. One feature of the oscillator that is inherent in its design is the rhythmic expression of a number of clock RNAs and daily oscillations in clock protein abundance. Analyses of mammalian and Drosophila transcriptomes using DNA microarrays identified a large number of clock-controlled genes that are involved in diverse physiological processes. Despite the centrality of cycling clock mRNA expression, more recent studies have highlighted the importance of post-translational mechanisms, in particular phosphorylation, in regulating clock protein abundance. In addition, posttranslational modifications of clock proteins are believed to regulate their transcriptional activity, subcellular localization, and protein-protein interaction.
Using a combination of biochemical, molecular genetics, and proteomic approaches, we hope to understand the biochemical and cellular basis of clocks, and the mechanisms by which they regulate organismal physiology.
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gcortopassi@ucdavis.edu
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VM Molecular Biosciences
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ssdavid@ucdavis.edu
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Chemistry
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scdawson@ucdavis.edu
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Microbiology and Molecular Genetics
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msdenison@ucdavis.edu
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Environmental Toxicology
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ediaz@ucdavis.edu
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Pharmacology - Medicine
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Functional genomics of nervous system development.
My lab's main research interest is to understand molecular mechanisms of nervous system development in rodent model systems. We use DNA microarrays as a tool to identify genes that are developmentally regulated during mouse brain development. Candidate genes are characterized with molecular and cellular techniques and transgenic mice. In particular, my lab is interested in two areas: neural proliferation and synapse development. We have identified several candidate molecules that increase in gene expression during the period of neural proliferation or synapse formation and we are currently studying the role of two molecules (Mad3 and SynDIG1) in these processes.
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spdineshkumar@ucdavis.edu
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Plant Biology
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Host-pathogen interactions;
Programmed cell death;
Autophagy;
Immune signaling;
Pathogen effector biology;
Protein microarrays;
Genomics and Proteomics
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gcdouglas@ucdavis.edu
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gdrakakaki@ucdavis.edu
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Plant Science
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Our research is focused on endomembrane trafficking in plant cells. A key area is how trafficking pathways control cell wall biosynthesis and polysaccharide deposition. Our group employs multidisciplinary research approaches, including the use of small molecules (chemical genomics), organelle proteomics and genetics.
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bwdraper@ucdavis.edu
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Molecular & Cellular Biology
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Germline stem cells
We study mechanisms that regulate the development and function of germline stem cell in zebrafish, with a main focus on female germline stem cells. We study factors that function within the stem cells, as well as those that are required for the development of the somatic gonad, the germ cell niche.
Sex determination and maitenance of the adult sexual phenotype
While zebrafish do not switch sex as adults, our lab has recently discovered that maintenance of the adult female sexual phenotype is an active process that requires continuous input from germ cells, as reduction of germ cell numbers in an adult female results in female-to-male sex reversal. Our current research is focused on determining what signal is produced by the germ cells and how it influences the developmental state of the somatic gonad.
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jengebrecht@ucdavis.edu
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Molecular & Cellular Biology
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Meiosis and checkpoint function in the C. elegans germ line
Germ cells are specialized cells that undergo mitotic proliferation followed by meiosis and cellular differentiation to generate haploid gametes for sexual reproduction. We are investigating several aspects of germ line biology using the nematode, Caenorhabditis elegans, as a model. The C. elegans germ line is particularly amenable to these studies due to its unique structural organization, the molecular genetics of the system, and the high degree of conservation with genes and pathways in humans.
We are currently investigating 1) how checkpoint pathways are differentially regulated in the female and male germ line; 2) how unpaired sex chromosomes of the heterogametic sex repair double strand breaks and are hidden from the checkpoint machinery; and 3) how different checkpoint pathways interact to ensure the faithful transmission of the genome.
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caerickson@ucdavis.edu
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Molecular & Cellular Biology
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Our research focuses on the development of the avian trunk neural crest. We are particularly interested in the mechanisms that segregate the neural crest lineage from the neural epithelium, the mechanisms that guide specific neural crest lineages along different migratory pathways, and the control of neural crest cell differentiation.
The laboratory uses a number of experimental approaches to address cellular and molecular aspects of neural crest development including: surgical manipulation, cell culture, in vitro embryo culture, in ovo electroporation of expression plasmids, and gene knockdown using antisense oligonucleotides and morpholinos.
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meetzler@ucdavis.edu
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Molecular & Cellular Biology
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Structure and function relationships, carbohydrate specificity, and physiological roles of plant lectins, particularly from Dolichos biflorus.
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mtfacciotti@ucdavis.edu
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Biomedical Engineering (Grad)
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Gene Regulatory Network - Evolution and Synthesis
We are interested in using the tools of Systems Biology to elucidate rules of biological assembly for gene regulatory networks and in turn use this knowledge, through Synthetic Biology approaches, to build novel circuits.
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rhfairclough@ucdavis.edu
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Neurology - Medicine
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My lab studies the molecular mechanics of agonist induced channel activation of the nicotinic acetylcholine receptor. We are also mapping the surface domains of the acetylcholine receptor that stimulate the production of pathogenic antibodies in the disease myasthenia gravis.
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mjferns@ucdavis.edu
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Anesthesiology & Pain Medicine
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Cellular and molecular basis of cholinergic synapse formation in mammalian nervous system.
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ofiehn@ucdavis.edu
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UC Davis Genome Center
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Metabolomics
The Fiehn research laboratory develops improved methods in analytical chemistry and bioinformatics to capture and utilize metabolomic data. These tools are employed to understand, which parts of larger biochemical networks respond to genetic perturbation or environmental stress.
Metabolomics applications follow a two-tiered approach: they can be used for sample discrimination and classification (e.g. for clinical diagnostics or GMO substantial equivalence), or for biochemical and mechanistic studies (e.g. for understanding the onset and progression of human diseases, or for detailing regulatory modules in cells or subcellular compartments). Therefore, the Fiehn research laboratory uses several biological models on organismal, tissue or cellular level which are detailed in the Projects page.
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ajfisher@ucdavis.edu
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Molecular & Cellular Biology
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Mechanistic Structural Biochemistry
Systems of focus include: Sulfate activation, Ferredoxin Dependent Bilin Reductases, & Sialyltransferases.
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pgfitzgerald@ucdavis.edu
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Cell Biology & Human Anatomy
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csfraser@ucdavis.edu
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Molecular & Cellular Biology
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jdfurlow (at) ucdavis (dot) edu
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Neurobiology, Physiology and Behavior
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Molecular basis of hormone action, particularly during development. Analysis of gene expression cascades during morphogenesis. Mechanisms of skeletal muscle atrophy and death.
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csgasser@ucdavis.edu
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Molecular & Cellular Biology
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Molecular basis of plant development and evolution of development.
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acgelli@ucdavis.edu
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Pharmacology - Medicine
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My lab studies the pathogenesis of human fungal pathogens with a focus on Cryptococcus neoformans - the leading cause of fungal meningoencephalitis. For the past several years we have focused on the activation and regulation of a plasma membrane calcium channel in fungal cells and its potential use as a therapeutic target. Our NIH funded research program is currently focused on a high-throughput small molecule and off-patent drug screen to identify specific blockers of the channel and assess their therapeutic potential for the treatment of cryptococcal infection. We use a multidisciplinary approach that includes electrophysiology, imaging, cell biology, animal models, and molecular biology to validate the hits identified in our screen and test their ability to clear cryptococcal infections in vivo.
Recently we have also become very interested in resolving the molecular mechanisms that facilitate the invasion of C. neoformans into the central nervous system. This interest was spearheaded in part by our study of the extracellular proteome of C. neoformans where we found that many of these secreted proteins are proteases and likely play a role in mediating fungal-host interactions. We have since developed an in vitro model of the blood-brain barrier and we have shown that it is a very useful system for defining the mechanisms of cryptococcal invasion into the CNS. In seeking to understand how C. neoformans crosses the blood-brain barrier, we recently discovered that it does so by means of a metalloprotease enzyme Mpr1, the presence of which we have also shown to be essential for establishing fungal disease in the central nervous system. The enzyme appears to selectively alter the surface of the blood-brain barrier by making it more permeable however the protein targets of this protease are unknown.
Our aim is to characterize the molecular mechanism of this key protease and screen for inhibitors. The long-term goal will examine whether this key protease can be coupled to nanoparticles to facilitate the movement of crucial drugs across the blood-brain barrier.
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paghosh@ucdavis.edu
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Biochemistry and Molecular Medicine
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Signal Transduction Pathways in Prostate Cancer
The pathways we study include the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, the Ras/Raf/MEK/MAPK pathway and other signaling pathways both upstream and downstream of these. This includes the mammalian target of rapamycin (mTOR) pathway, and signaling by the epidermal growth factor receptor (EGFR), related receptor tyrosine kinases ErbB2 and ErbB3.
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cgiulivi@ucdavis.edu
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VM Molecular Biosciences
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tmglaser@ucdavis.edu
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Cell Biol & Human Anatomy
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Genetic basis of mammalian eye development and congenital eye malformations
We study genetic mechanisms of vertebrate eye development, evolutionary conservation of gene networks, and transcriptional regulation. Our major interests include early patterning of the optic primordia and retinal cell fate specification. We use mutant and transgenic mice, human pedigrees segregating congenital eye malformations, and a variety of genomic, molecular and cell-based techniques. Current lab projects focus on ganglion cells – the first-born retinal neurons whose axons form the optic nerves and relay all visual information from the eye to the brain, fate symmetry, bHLH transcription factors, Notch signaling, the retinoid pathway, and molecular identification of new eye disease loci.
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avgomes@ucdavis.edu
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Neurobiology, Physiology and Behavior
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Role of Proteasomes and Troponins in cardiac and skeletal muscle tissues. Protein degradation and cardiomyopathies.
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qzgong@ucdavis.edu
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Cell Biology & Human Anatomy
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Brain development is a finely orchestrated process. Transient abnormalities, such as delayed or excessive growth of axons and dendrites in neurons can have a prolonged impact in the formation of functional connections. Early postnatal stages are critical periods, in which both intrinsic genetic programs and sensory experience participate in the formation and refinement of functional circuitry. My lab uses mouse olfactory system as a model to study the molecular mechanisms of neuronal network formation and plasticity. Using a combination of cell biological, genetic and molecular biological approaches, we are focused on studying molecules that regulate olfactory sensory axon growth and guidance, mitral cell dendritic differentiation and olfactory circuitry formation.
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pjhagerman@ucdavis.edu
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Biochemistry and Molecular Medicine
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nhagiwara@ucdavis.edu
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Cardiology (Internal Med)
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Development and disease of skeletal muscle and the heart
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fghaj@ucdavis.edu
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Nutrition
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Molecular and cellular basis of obesity and diabetes
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bdhammock@ucdavis.edu
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UCD Cancer Research Center
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The laboratory has several major areas. We are interested in control of development by chemical mediators in mammals and insects. In mammals we work on enzyme regulation of epoxyeicosanoids that control hypertension and inflammation. In insects we study the hormones that control metamorphosis. We also work on the development of high throughput systems for metabolite profiling by mass spectrometry and by immunoassay.
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jjharada@ucdavis.edu
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Plant Biology
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Molecular, genetic, biochemical, and genomic dissection of embryogenesis and seed development in plants.
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slharmer@ucdavis.edu
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Plant Biology
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Understanding the molecular basis of circadian rhythms in plants and how these daily rhythms affect plant physiology.
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dominik.haudenschild@ucdmc.ucdavis.edu
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Orthopedics (School of Medicine)
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Osteoarthritis Animal Model and Biomarkers
Osteoarthritis is a painful and debilitating disease that results in loss of joint function. Because cartilage is an aneural and avascular tissue, patients often do not seek medical advice until there is irreversible loss of cartilage. At that stage, painful bone-bone contact occurs in the joints. Knee and hip osteoarthritis is often the end-stage result of silent pain-free chronic cartilage degradation that occurs over years or even decades. A portion of my lab is dedicated to identifying serum biomarkers of this pre-arthritic cartilage degradation. The goal is to create a screen which can be routinely used by physicians to identify patients at risk for joint failure due to osteoarthritis, in a similar fashion as serum cholesterol levels are currently used to identify patients with silent cardiovascular disease that are at risk for heart failure or stroke.
Minor joint injuries, such as an ACL or meniscus tear, ultimately lead to arthritis in most cases. The damage that initiates arthritis begins almost immediately at the cellular level. Despite this, current clinical care of ACL tears does not address the initial damage that leads to future arthritis. We have developed a non-surgical mouse model of ACL tears, in which we study the cellular responses to this type of injury, with the goal of developing intervention strategy at the time of injury to prevent future arthritis.
Chondrocyte Mechanotransduction
Most people understand that lifting weights will increase muscle mass, loss of activity causes unused muscles to shrink, and too much activity can lead to injury. It turns out that the same is true for cartilage: moderate mechanical loads are required for cartilage homeostasis. Too little, or excessive loading causes cartilage matrix to be lost or damaged. Mechanotransduction is the process through which cells within cartilage sense the mechanical forces and convert them to biochemical signals. A portion of my lab studies mechanotransduction, the interactions between the chondrocyte cytoskeleton and signal transduction events which lead to the regulation of gene expression and extracellular matrix synthesis that is required for the maintenance of health cartilage.
Growth Factor-Matrix Interactions
Our recent discovery is that Cartilage Oligomeric Matrix Protein (COMP) is a multivalent TGF-beta binding protein, and that COMP-bound TGF-beta has more activity than free unbound TGF-beta. We are exploring the ability of COMP to augment TGF-beta activity in cartilage and bone tissue engineering applications, and mapping the binding exact binding site to get a better understanding of the mechanisms involved.
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wdheyer@ucdavis.edu
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Microbiology and Molecular Genetics
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Mechanism and regulation of recombinational DNA repair
Double-stranded DNA breaks (DSBs) are among the most genotoxic lesions and can be generated by ionizing radiation, drugs, or cellular processes. In eukaryotes, several pathways compete for the repair of such lesions. Homologous recombination is the critical DSB repair pathway in yeasts and an important DSB repair pathway in all eukaryotes studied. We are using primarily Saccharomyces cerevisiae as a model system and employ genetical, molecular, and biochemical methods to elucidate the molecular mechanism of homologous recombination and recombinational DNA repair and its regulation by the DNA damage checkpoints.
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jekhildreth@ucdavis.edu
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Molecular & Cellular Biology
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My laboratory research is focused on understanding mechanisms by which HIV subverts host pathways and molecules during its replication cycle. We are particularly interested in the role of cholesterol and cholesterol homeostatic pathways in virus entry, virus release and viral gene transcription. The involvement of cholesterol-rich lipid rafts, late endosomes and exosomes is also the subject of investigations in our laboratory. Another major area of interest is the impact of viral co-infections on HIV’s tropism and replication. Many viruses are known to modulate cholesterol regulatory pathways and cellular cholesterol content and thereby can profoundly affect HIV replication. We are interested in this and other mechanisms of enhancement or suppression of HIV transmission and replication by co-infecting viruses.
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mhorne@ucdavis.edu
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nhunter@ucdavis.edu
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Microbiology and Molecular Genetics
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Homologous Recombination.
The mechanism and regulation of chromosome repair by homologous recombination and its role in chromosome transmission and genome stability.
Post-Translational Protein Modification in Meiosis.
The nature and function of post-translational modifications of proteins involved in homologous recombination during meiosis.
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kinoue@ucdavis.edu
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Plant Science
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Gene Duplications
What is their biological significance? We address this question by comparing properties and functions of two sets of prokaryote-derived homologous proteins in chloroplasts (protein translocation channel Toc75 and its paralog OEP80/Toc75-V; three type I signal peptidases, Plsp1, Plsp2A, Plsp2B).
Organelle Biogenesis - Protein evolution
How did the protein import channel in the organelle envelope evolve from a protein in the outer membrane of an ancestral cyanobacterium? We elucidate the functions and sorting/assembly mechanisms of Toc75 and OEP80/Toc75-V, which are homologous to a family of proteins essential for the viability of Gram-negative bacteria.
Organelle Biogenesis - Development of Membrane System
How do the intraorganellar membrane systems develop? We take three strategies. Strategy 1 is to define the molecular bases underlying thylakoid disruption due to the lack of signal peptide processing. In strategy 2, we elucidate the mechanism by which Plsp1 is sorted to the envelope and thylakoid within a chloroplast. In strategy 3, we attempt to address how citrus fruit peel changes its color from green to orange, then back to green. (dis-assembly and re-assembly of thylakoids).
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yizumiya@ucdavis.edu
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Dermatology - Medicine
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Epigenetic gene regulation by using herpesvirus reactivation as a model system. Epigenetic components of chromatin, including host and viral factors that interact to facilitate both the establishment and maintainance of the chromatin state as well as the molecular transitions that take place during reactivation (“chromatin remodeling”). Post-translational modifications that are imparted on critical viral and host factors are also an area of research in our lab.
Protein methylases and demethylases that regulate breast cancer cell growth
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kbkaplan@ucdavis.edu
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Molecular & Cellular Biology
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My laboratory is interested in understanding how chromosomes are accurately segregated during mitosis. We study the normal events of mitosis using the model organism, the budding yeast Saccharomyces cerevisiae. We study abnormal mitotic events associated with human disease using colorectal cancer as a model.
To understand how chromosome segregation is coordinated with anaphase events, we have focused on kinetochore-passenger complexes. Kinetochore-passenger complexes transit between kinetochores and the anaphase spindle where they are believed to coordinate chromosome movements with events in anaphase. We are interested in how kinetochore-complexes assemble during anaphase, which anaphase events are coordinated by kinetochore-passenger complexes and the mechanisms by which these complexes regulate anaphase events to ensure their proper order (e.g., anaphase spindle elongation and cytokinesis).
To understand how chromosome segregation is compromised in human cancers, we are examining chromosome instability (CIN) in colorectal tumor cells. We have found that mutations in the tumor suppressor gene, adenomatous polyposis coli (APC), contribute to failures in chromosome segregation. We have shown that mutations in APC compromise the ability of microtubules to make plus-end attachments in mitotic cells. Our finding that this phenotype is genetically dominant has important implications for patients that have a single mutant copy of APC. We are currently exploring the mechanisms by which mutations in APC compromise plus-end microtubule attachment and how this cellular phenotype may contribute to the progression of colorectal cancer.
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jinoh.kim@ucdmc.ucdavis.edu
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Pediatrics - Medicine
Lab
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We study export of proteins from the endoplasmic reticulum and consequences of abnormal ER export in vivo and in vitro.
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Plant Science
Lab
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Quantitative Systems Biology
We focus on two major questions using plant natural chemistry as our model system. Plant natural chemistry generates compounds that provide the taste, flavor, color and medicinal activities that people associate with specific plants. However, their primary role appears to be helping the plant cope with its environment by attracting pollinators, repelling attackers and protecting the plant from sunlight. These aspects make these compounds easy to measure and key tools in understanding modern systems biology and genomics.
The first question that we use these chemicals for is to understand how thousands of genes coordinate within a system to control the proper functioning of the system. This involved modern quantitative genomics and tools such as genome wide association mapping and QTL analysis. We are at the forefront of developing network analysis approaches and theory to help with the modern synthesis of the gene-to-phenotype linkage.
The second question we focus on is why plants make these chemicals. They have broad activities and plants make an amazing diversity of chemicals, each potentially with its own function and evolutionary history. We are primarily using the model plant, Arabidopsis thaliana, to study how its secondary metabolites control interactions with both insects and fungi. As a part of this we are using a mixture of functional genetics, quantitative genetics, plant biology, evolutionary biology and metabolite profiling to develop as in depth and broad a picture as possible. To broaden this picture, we are expanding into rice, tomato, Lycopersicon, and grapes, Vitis.
An additional avenue that we are pursuing is the fact that fungi also make secondary metabolites. For instance, Botrytis cinerea produces a suite of secondary metabolites whose main role appears to be killing plant cells. Thus by studying how Arabidopsis and Botrytis interact, we hope to analyze how organisms can combat each other through metabolism. We are expanding our quantitative systems approaches to study genetic variation in both the host and pathogen of this system simultaneously.
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knoepfler@ucdavis.edu
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Cell Biology & Human Anatomy
Lab
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The research in the Knoepfler lab focuses on the epigenetic and transcriptional control mechanisms that direct cell fate.
We are particularly interested in the relationship between tumorigenicity and pluripotency.
Our model systems including both mouse and human ESC, induced pluripotent stem (iPS) cells, and cancer stem cells.
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aaknowlton@ucdavis.edu
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Cardiovascular Physio(IntMed)
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The work in our laboratory focuses on the cardiovascular system. Most of our work centers on three areas: 1. Role of HSP60 in apoptosis and heart failure. In particular, we are interested in whether HSPs in heart failure paradoxically have a detrimental effect on the heart mediated by the immune system and an inflammatory response. 2. Mitochondrial fission, fusion and function in heart failure. 3. Estrogen, aging and inflammation. We are interested in the role of aging vs. estrogen loss on changes in the vasculature and the acceleration of atherosclerosis with menopause, and loss of endothelial progenitor cells leading to impaired vascular repair. Our research concentrates on cardiovascular function/physiology primarily at the cellular and organ level.
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akopp@ucdavis.edu
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Evolution and Ecology
Lab
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Our lab combines developmental and evolutionary genetics to understand the origin of new phenotypes and ecological adaptations. Our interests include the evolution of developmental pathways, the origin of sex-specific morphological traits, evolution of insect behavior and host plant preferences, and molecular mechanisms and ecological impact of insect-bacterial symbiosis. We address these questions by integrating molecular-genetic, genomic, quantitative-genetic and phylogenetic approaches in a variety of Drosophila species.
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ifkorf@ucdavis.edu
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Molecular & Cellular Biology
Lab
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Genomics & Bioinformatics
High-throughput technologies are transforming biology, medicine, agriculture, and related fields. Biology is now incredibly data-rich and requires computers to organize and analyze the data. My research program mixes -omic technologies and information technology to make new discoveries in genome structure and function. My lab is highly collaborative, and we always welcome potential research partners. My students can all do lab work and program, and many are co-mentored. Current interests include gene prediction, genome assembly, sequence alignment, DNA-protein interactions, intron function, and epigenetics.
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sckowalczykowski@ucdavis.edu
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Microbiology and Molecular Genetics
Lab
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Biochemical mechanism of genetic recombination and DNA repair; DNA helicases and motor proteins; Physical and structural aspects of protein-nucleic acid interactions; Single-molecule biophysics; Nanotechnology; Cancer biology.
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jmlabavitch@ucdavis.edu
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Plant Science
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Plant Cell Wall Research
My colleagues and I focus our research attention on aspects of plant development in which plant cell wall metabolism plays an important role. This includes studies of fruit ripening and the interactions of pathogens and insect pests with plants. In recent years our studies have also included aspects of cell wall disassembly that might be controlled and enhanced in order to optimize the generation of biofuels from crop plant "residues".
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jclagarias@ucdavis.edu
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Molecular & Cellular Biology
Lab
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Molecular Photobiology
Research in my lab focuses on phytochromes, a family of light sensing biliproteins found in plants, photosynthetic bacteria and even nonphotosynthetic eubacteria and fungi, and cyanobacteriochromes, phytochrome-related biliprotein sensors that have proliferated in cyanobacteria. Phytochromes mediate responses mainly to red and far-red light in the environment that are particularly important to shade sensing. Cyanobacteriochromes sense light from the near UV to red region to optimize light energy conversion by the oxygenic photosynthetic apparatus. Our investigations are biochemical in nature focusing on structure-function and evolutionary relationships of these light sensors and the enzymes responsible for the synthesis of their linear tetrapyrrole (bilin) prosthetic groups. The long-term goal of these investigations is to rationally alter the natural responses of plants and cyanobacteria to their light environment for optimum biomass yield and/or light energy conversion.
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jalast@ucdavis.edu
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Pulmonary (Internal Medicine)
Lab
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wsleal@ucdavis.edu
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Entomology
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Research in my lab is aimed at unraveling the molecular mechanisms that make the insect’s olfactory system so sensitive and selective. Insect prominence among other animals is due in large part to a key physiological element for their survival and reproduction - a refined olfactory system. Olfaction is orchestrated at various levels starting with reception of odorants at the periphery, processing and integration of olfactory and other sensory modalities in the brain, and ultimately translation of olfactory signal into behavior. Thus, the cornerstone of a sophisticated olfactory system is the ability of the insect’s peripheral system to selectively detect and rapidly inactivate minute amounts of odorants. Reception of odorants is mainly mediated by three olfactory proteins, namely, odorant-binding proteins (OBPs), odorant receptors (ORs), and odorant-degrading enzymes (ODEs). OBPs are involved in the uptake, transport and delivery of odorants to ORs. By using biochemical, electrophysiological, RNAi, and kinetic studies we have demonstrated that OBPs are essential for the sensitivity of moth’s olfactory system. In collaborations with structural biologists, including UC Davis colleagues, we study the molecular mechanisms of odorant binding, release, and transport, including novel, pH-dependent conformational changes in moths and mosquitoes. By comparative kinetic studies of odorant degradation by recombinant and native enzymes we have demonstrated for the first time that ODEs are involved in the fast inactivation of odorants. Using bioinformatics and molecular approaches coupled with the Xenopus oocyte recording system we investigate how ORs contribute to the selectivity of the insect’s olfactory system.
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jaleary@ucdavis.edu
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Molecular & Cellular Biology
Lab
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CURRENT RESEARCH
My current research interests include four main areas:
- Structural characterization of proteoglycans and protein:carbohydrate binding partners involved in immunology and infectious disease
- Differentiation of Protein:Protein and Protein:Ligand complex conformations including proteomics as it applies to analysis of viral recruitment of the human ribosome/eukaryotic initiation factors and mapping of the protein modifications of the ribosomal protein subunits
- Determination of mechanisms of enzyme catalysis via measured kinetic constants and examination of enzyme-substrate and enzyme-inhibitor complexes particularly those involved in sulfation and phosphorylation
- Analysis of virulence factors associated with M. tuberculosis
(This research is currently supported by 5 NIH grants; Two RO1 for which I am PI, one PO1 for which I am a co-PI (Doudna PI – U.C. Berkeley) and two subawards (Bertozzi PI – U.C. Berkeley and Moore PI – Oklahoma Medical Research Foundation). Additionally, last year I obtained funding ($500,000) for a new campus high resolution mass spectrometer that is housed in the Satellite Facilities, for which I am Campus Director through the office of the Vice Chancellor for Research.)
GLYCOCHEMISTRY IN IMMUNOLOGY AND INFECTIOUS DISEASES
Research currently being conducted in my group includes the use of both Fourier transform ion cyclotron resonance (FTICR), ion trap mass spectrometry in combination with collision induced dissociation (CID) and Ion Mobility MS (IMS) for probing molecular structure and conformational changes. These techniques are used in the development of novel methodology for the characterization of carbohydrate structure in a variety of biological systems. My group and I have developed several software programs that allow for carbohydrate sequencing and compositional analysis in tandem with new methods that we developed for structurally characterizing proteoglycans. This research has advanced now to the area of protein-carbohydrate interactions in which we are analyzing chemokine-glycosaminoglycan non-covalent complexes involved in chemotaxis and inflammation. Specific goals include:
- Sequence and compositional analysis of heparin/heparan sulfate derived from the extracellular matrix of various healthy and diseased cells specifically as it relates to structure-function relationship. Particular emphasis is on GAG:Chemokine, Chemokine:G-protein coupled receptor and GAG:Chemokine:Receptor interactions.
- Investigation of mycobacteria cell constituents including development of methods for the analysis of virulence factors associated with M. tuberculosis.
Chemokines, small chemotactic proteins, have been shown to bind GAGs both in vitro and in vivo, and recently it was demonstrated that this interaction is required for their function in vivo. Immobilization of chemokines on GAGs is thought to enhance their local concentration and facilitate the formation of chemokine gradients to guide the migration of cells, especially under flow conditions. GAG-binding may also help recruit chemokines to specific populations of cells, thereby contributing to the control of cell migration in a receptor independent way. An emerging hypothesis is that glycosaminoglycans (GAGs) play a role in the in vivo function of chemokines, and that specificity in these interactions could alter the apparent redundancy of the chemokine:receptor interaction.
In this particular area of research we are developing and utilizing mass spectrometric techniques that will allow us to analyze the non-covalent complexes of GAG-Chemokine, Chemokine-Receptor and eventually GAG-Chemokine-Receptor assemblies. (At left is a crystal structure we solved showing the binding site of the GAG drug, Arixtra bound at the dimer interface of eotaxin, a known chemokine upregulated in asthma.) Specific questions we will address include:
- Do different chemokines bind GAG’s with different affinity?
- What role does multimerization play in GAG binding?
- Is there GAG sequence specificity in binding?
- What are the structures of the GAG:Chemokine complexes?
- How do these interactions affect inflammation and disease in vivo?
- What, if any, conformational differences of the GAG or Chemokine are critical to binding?
A considerable amount of productivity has also ensued on structural elucidation of mycobacterium (tuberculosis and other strains) virulence factors. Strong collaborations exist with the Bertozzi (UC Berkeley), Cox (UCSF) and Carroll (U. Michigan) laboratories in which our lab is responsible for all methods development for the successful analysis of lipid metabolites as well as identifying enzyme binding partners involved in virulence pathways. A recent publication of ours appeared in Chemical Biology in which we have determined the complete structure of a Vitamin K, menaquinone derivative that is clearly related to virulence. A podcast taped by the journal can be accessed through the journal.
(This research is currently funded by NIH R01 GM47356 and R01 AI51622)
ENZYMOLOGY AND PROTEIN-LIGAND INTERACTIONS
Sequencing of the human genome, and the genome of numerous pathogens, has resulted in an explosion in the number of studies aimed at identifying potential drug targets. A key step in this effort, and one of the significant challenges, is to identify and characterize disease-associated proteins and enzymes, and, for the latter, to understand their specific mechanisms of action. This information is crucial for the discovery and optimization of lead molecules that target these proteins, as is the development of high throughput screening methods aimed at identifying substrates and inhibitors.
We are developing direct, mass spectrometry-based assay methods that are very sensitive, require no additional time or effort than traditional UV based methods, and eliminate the need for a chromophore or radiolabel. The major areas currently being investigated include:
- Enzyme immobilization and multiplex screening of combinatorial libraries of possible enzyme inhibitors.
- Determination of kinetic parameter such as Km, and kcat of specific enzymes as they relate to various substrates using a novel mass spectrometric method.
- Determination of Ki values for inhibitors identified in the screening process and simultaneous determination of mechanisms responsible for inhibition.
- Protein expression and unambiguous determination of the mechanisms (i.e. random, sequential, Ping-Pong) associated with various enzymes. Our new MS methods include isolating and identifying any intermediates using both digestion and stable isotope labeling techniques.
- Isolation and investigation of the enzyme-ligand non-covalent and covalent complexes and calculation of Kd values using gas-phase and solution phase data.
Non-covalent complexes of the enzyme with both substrate and inhibitor are also being generated and analyzed using mass spectrometry and Kd values measured for both the substrate-enzyme and the inhibitor-enzyme complexes. The ratio of dissociation constants determined from the gas phase data matches that of the solution values thus suggesting that the solution complexes can be measured directly using mass spectrometry. We anticipate that the significant progress made in this area will lead to investigations of protein-protein interactions and thus will aid in answering important questions about this area of biochemistry. (This research is currently funded by NIH R01 GM63581 and RO1 HD056022)
RIBOSOME RECRUITMENT BY VIRUSES AND ATTENDING PROTEIN MODIFICATIONS
The ribosome, the cellular catalyst of protein synthesis, is one of the largest and most complex biological macromolecules. We are currently involved in a collaborative research project to test the hypothesis that the ribosome and its component subunits exist in multiple functional states in human cells. Preliminary evidence suggests that distinct forms of the ribosome, differing by one or a few component proteins, may play critical roles in the control of gene expression during viral infection. Upon infection by viruses such as hepatitis C, an internal ribosome entry site (IRES) RNA binds to host cell ribosomes and recruits them for viral protein synthesis. Ribosome-IRES complexes are separated from ribosomes incapable of IRES recognition, and the components of each sample analyzed by ESI-FTICR and HD-MS Ion Mobility mass spectrometry.
These MS methods are used to probe protein complexes that comprise mammalian ribosomes, and the accompanying initiation factors, both before and after infection with Hepatitis C virus. The post-translational modifications found to protein complexes have been extremely interesting, particularly those showing phosphorylation and sulfation. One of our recent manuscripts published in Nature Methods, describes a first time protocol for detecting tyrosine sulfation and determining the temporal resolution of sulfation on N-terminal GPCR. As part of this project, I installed a new design mass spectrometer (Waters Synapt HDMS), capable of detecting megadalton protein complexes. This particular instrument was the first of its kind installed in the United States. This instrument has allowed for the analysis of protein:protein and protein:carbohydrate binding partners. The eukaryotic initiation factor 3, shown above, is one such complex with a mass of 800,000 Da which we have successfully analyzed and determined the subunit interactions.
Experiments are underway which involve denaturing the human ribosome complexes and analyzing the constituent proteins by LC-ESI-FTICR and IM mass spectrometry using both a bottom up and top down approach. Data thus far collected indicate all 32 proteins from both the native and IRES recruited 40 S ribosome have been identified; many contain various post-translational modifications. The eIF3 complex of the IRES recruited ribosome has also been investigated and sites of phosphorylation have been unambiguously identified. Equally important is the fact that we have probed the interaction of the various subunits and are now looking at conformational differences/folding and unfolding during complex disruption. Technology developed in the course of this project will be valuable to the study of many macromolecular complexes that play central roles in the control of gene expression. (This research is currently funded by NIH PO1 GM073732)
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jian-jian.li@ucdmc.ucdavis.edu
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slin@ucdavis.edu
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Microbiology and Molecular Genetics
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Molecular mechanisms of Calorie Restriction and Aging
Regulation of NAD+ metabolism
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yflin@ucdavis.edu
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Anesthesiology & Pain Medicine
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Cellular and molecular physiology of ion channels: structure-function relationship and modulation
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bliu@ucdavis.edu
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Plant Biology
Lab
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Cell biology of the cytoskeleton and intracellular motility in plant and fungal cells. The dynamics of microtubules and actin microfilaments during plant cell division and cell growth. Roles of kinesin motor proteins in mitosis and cytokinesis. Molecular mechanisms of cytoskeleton-mediated hyphal growth in filamentous fungi. Arabidopsis thaliana, Oryza sativa (rice), and Gossypium hirsutum (cotton) as model systems for plant studies, and Aspergillus nidulans as a model for fungal studies.
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shlo@ucdavis.edu
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Biochemistry and Molecular Medicine
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Our overall research interests are to understand the molecular mechanisms that underlie the structure and function of focal adhesions. Focal adhesions are integrin-mediated junctions that attach a variety of different cell types to their underlying substratum. They are signal transduction organelles and play a major role in diverse biological processes, including cell growth, attachment, migration, death, polarization, and differentiation. As such, focal adhesion dysfunction is known to have profound repercussions in embryogenesis, tissue development and repair, as well as in many pathological conditions including various forms of cancer.
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selott@ucdavis.edu
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Evolution and Ecology
Lab
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Our research focuses on how genetic variation in translated through the developmental process into phenotypes, and how these phenotypes evolve. The importance of sequence changes that affect development to morphological evolution has been well established. But the phenotypic consequences of mutations that alter developmental regulators are often muted by the systems that buffer development against variation encountered in ontogeny. By studying the relationship between mutation and developmental phenotype, we gain insight into both the molecular forces that drive and constrain phenotypic evolution and the systems that keep development robust. To pursue these questions, we use a combination of genetic, genomic, computational, and imaging techniques, primarily in the model system of Drosophila.
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aylouie@ucdavis.edu
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Biomedical Engineering (Grad)
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Molecular imaging, cellular imaging, development of diagnostic and therapeutic agents, magnetic resonance imaging, novel contrast agents, fluorescence microscopy, multimodal imaging and imaging agents. Applications to cardiovascular, pulmonary and other disease systems.
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vmartinezcerdeno@ucdavis.edu
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Pathology - Medicine
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Stem and progenitor cell properties and behavior in the normal and pathogenic developing cerebral cortex, with an emphasis in autism. Stem and progenitor cells as treatment for traumatic and neurodegenerative diseases. Stem and progenitor cell role in the evolution of the cerebral cortex.
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fjmcnally@ucdavis.edu
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Molecular & Cellular Biology
Lab
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Meiosis is a process by which animals, plants and fungi reduce chromosome number four-fold to produce haploid gametes. In females of both plants and animals, only one of four sets of chromosomes segregated during meiosis is inherited by a gamete. In animals, this asymmetric inheritance is mediated by asymmetric meiotic spindle positioning and highly asymmetric cell divisions that yield a large haploid egg. We are interested in the mechanisms that mediate these asymmetric divisions and utilize C. elegans because both meiotic divisions can be filmed in utero using fluorescent protein fusions and time-lapse imaging. We use a combination of classical genetics, RNAi and biochemistry to elucidate the roles of proteins that regulate microtubule-based motility, microtubule organization and microtubule dynamics in meiotic cell division.
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mmudryj@ucdavis.edu
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Microbiology - Medicine
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Prostate cancer, Retinoblastoma (RB) E2F transcription factors, Androgen Receptor
Prostate carcinoma is the most commonly diagnosed cancer in men, and the second leading cause of death due to cancer in Western civilization. Androgen ablation therapy is effective in treating androgen-dependent tumors, but eventually, androgen-independent tumors recur and are refractory to conventional chemotherapies. Tumor recurrence is often due to reactivation of androgen receptor (AR) signaling but is also accompanied by deregulation of cell cycle and proliferative controls. The mechanism by which AR promotes proliferation has not been established. The RB/E2F pathways has been shown to be deregulated in prostate tumors, but recent studies indicate that E2F3 overexpression is predictive of a poor clinical outcome. However it is currently unknown how E2F3 contributes to tumorigenesis. My lab is dedicated to defining the molecular mechanisms that govern tumor progression. We currently have three main projects in the lab:
1. Regulation of AR dependent gene expression and cellular proliferation in prostate cancer
2. The interplay between E2F3 overexpression, RB deregulation and the AR in prostate tumorigenesis
3. The role of E2F3B isoform in prostate tumorigenesis
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jenatzle@ucdavis.edu
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Molecular & Cellular Biology
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Gene regulation, especially steroid hormone regulation of gene expression in Drosophila. Molecular mechanisms of morphogenesis and differentiation of epithelia during embryogenesis and imaginal disc development at metamorphosis. Drosophila developmental biology and developmental genetics. Identification and characterization of steroid biosynthesis pathways in insects.
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lonavarro@ucdavis.edu
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Microbiology and Molecular Genetics
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jan.nolta@ucdmc.ucdavis.edu
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jmnunnari@ucdavis.edu
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Molecular & Cellular Biology
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My laboratory is interested in the mechanisms that govern the behavior of mitochondria in cells.
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meodonnell@ucdavis.edu
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Physiology and Membrane Biology
Lab
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Stroke, cerebral edema, diabetes, estrogen, brain microvascular endothelial cells, astrocytes, Na transporters
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reparales@ucdavis.edu
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Microbiology and Molecular Genetics
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Bacterial degradation of aromatic hydrocarbons and man-made environmental pollutants. Bacterial chemotaxis to pollutants and man-made chemicals.
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japayne@ucdavis.edu
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Physiology and Membrane Biology
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Ion and water homeostasis of excitable cells
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david.pleasure@ucdmc.ucdavis.edu
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Neurology - Medicine
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My laboratory uses cell and molecular biological techniques to study the development and regeneration of the nervous system. Our current focus is on mechanisms of death and regeneration of oligodendroglia, the myelin-forming cells of the central nervous system, that take place during experimental autoimmune encephalomyelitis.
Genetic and epigenetic regulation of neural stem cell lineages
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jspowell@ucdavis.edu
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Hematology-Oncology (Int Med)
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tpowers@ucdavis.edu
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Molecular & Cellular Biology
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Mechanisms that regulate cell growth in the model eukaryote, the budding yeast S. cerevisiae, with emphasis on the TOR (target of rapamycin) signal transduction pathway. We are particularly interested in how this pathway regulates gene expression in response to intracellular as well as environmental cues.
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mlprivalsky@ucdavis.edu
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Microbiology and Molecular Genetics
Lab
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Our research focuses on understanding how cells regulate their proliferation and differentiation and the aberrant events which lead to neoplasia. Our specific goal is a better understanding of the actions of the nuclear receptors (also known as nuclear hormone receptors) in normal cells and in disease. Nuclear receptors are a family of hormone-regulated transcription factors, and include the steroid, retinoid, and thyroid hormone receptors; collectively they play critical roles in vertebrate homeostasis, differentiation, and reproduction. Nuclear receptors bind to specific target genes and modulate gene expression in response to hormones of extracellular origin, Intriguingly, these receptors can either repress or activate transcription by recruiting partner proteins denoted corepressors and coactivators. An alpha-helical domain (helix 12) at the C-terminus of these receptors functions as a hormone-regulated “molecular toggle switch;” by altering its conformation, helix 12 determines whether a corepressor or a coactivator is recruited to the nuclear receptor.
Notably, defects in the operation of the helix 12 toggle switch result in aberrant corepressor and coactivator acquisition and, as a result, human disease (including both endocrine and neoplastic disorders). Our research seeks to employ these aberrant receptors as tools to determine the molecular pathways that operate in human diseases and to elucidate the actions of the normal receptors in the normal cell. We are currently investigating the contributions of nuclear receptor function in normal adipose cell differentiation, in thyroid hormone resistance, in leukemia, and in renal clear cell and hepatocellular carcinomas.
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rhrice@ucdavis.edu
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Environmental Toxicology
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Biochemistry and expression of specific markers in epidermal cells and appendages
Mechanisms of action of toxic and physiological agents affecting keratinocyte growth and differentiation
Metabolic activation of toxic agents in keratinocytes
Evolution of keratinocyte differentiation markers
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abrose@ucdavis.edu
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Molecular & Cellular Biology
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The effect of introns on gene expression.
Introns are often dismissed as junk DNA, but they can have huge effects on gene expression through mechanisms that are not yet understood. I am investigating this interesting phenomenon in plants using molecular genetics, and by testing bioinformatic insights generated by Dr. Ian Korf and his group.
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lsrose@ucdavis.edu
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Molecular & Cellular Biology
Lab
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Developmental and cell biology of C. elegans, with an emphasis on the control of cell division patterns and polarity.
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jmscholey@ucdavis.edu
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Molecular and Cell Biology, University of California at Davis, California, USA.
Lab
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Molecular Cell Biology. Mitosis, ciliogenesis, intracellular transport and motor protein functions. Specific Projects: 1. Mechanisms of mitosis and chromosome segregation in the Drosophila embryo (funded by NIH grant GM55507): 2. Kinesin-2 motors, intraflagellar transport and sensory cilium biogenesis in C. elegans neurons (funded by NIH grant GM50718). Technical approaches; molecular biology and protein biochemistry; light microscopy and the elucidation of protein dynamics and function in cells; quantitative modelling.
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djsegal@ucdavis.edu
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UC Davis Genome Center
Lab
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• Engineered DNA-binding proteins as therapeutics and molecular tools for genomics.
Almost every disease has a genetic component. Often this information is used only to determine how condemned a person is to develop disease. We would like to use the genetic information to fix the disease. A guiding principle for our work has been to study how nature does what it does, then attempt to use that knowledge to make useful tools to improve public health, either through increased knowledge or therapeutic intervention. Specific research foci in the Segal Lab revolve around engineering custom zinc finger DNA-binding proteins for specific applications. We also continue to make methodological improvements, many of which have been widely adapted in the field.
Specific research foci in the Segal Lab revolve around engineering custom DNA-binding proteins for the following applications:
• Genetic variation and human diseases: SNP functions in Coronary Artery Disease
• Gene therapy: epigenetic therapy for Angelman and Rett Syndromes
• Gene therapy: permanent disruptors of the HIV genome
• Zinc finger and TAL effector proteins: targeted nucleases, transposases, transcription factors.
• Biology of human zinc finger transcription factors: role of genetic variation
• Probes and diagnostic tools of genetic and epigenetic information
Structure/function of DNA-binding proteins and their application in functional genomics and gene therapy; protein engineering of sequence-specific therapeutics and molecular tools that can modify target genes in the human genome.
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email: kshiozaki(at)ucdavis.edu
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Microbiology and Molecular Genetics
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My laboratory utilizes fission yeast as a genetically amenable model system to elucidate the regulation and function of the stress MAPK cascade and the TOR (Target Of Rapamycin) signaling pathway.
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mhsinger@ucdavis.edu
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Microbiology and Molecular Genetics
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Microbial development, gene regulation, and transcriptional control of gene expression.
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jvsolnick@ucdavis.edu
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Infectious Diseases (Int Med)
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dastarr@ucdavis.edu
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Molecular & Cellular Biology
Lab
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There are many examples throughout development where nuclei or other organelles migrate to a new position in the cell. Once the nucleus has migrated to the correct location, there are mechanisms to anchor the nucleus there. Defects in nuclear positioning can lead to developmental defects and diseases such as Lisencephaly and Muscular Dystrophy. However, very little is known about the mechanisms of nuclear positioning. We are using the Nematode Caenorhabditis elegans as a model organism to study how nuclei and other organelles are positioned within a cell. We use genetic, biochemical and molecular approaches to study this basic problem in cell biology.
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casweeney@ucdavis.edu
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Biochemistry and Molecular Medicine
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Receptor tyrosine kinases in breast tumor progression and therapeutic resistance
Tumor suppressors & oncogenes in breast cancer
Mouse models of breast cancer
Impact of psychosocial stress on breast tumor initiation, progression, regression & recurrence
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ftablin@ucdavis.edu
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Vet. Anatomy & Cell Biology
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ytakada@ucdavis.edu
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Dermatology - Medicine
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aftarantal@primate.ucdavis.edu
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Pediatrics - Medicine
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Regenerative Medicine,
Gene Therapy,
Stem/Progenitor Cells and Transplantation,
Fetal:Maternal Microchimerism,
In vivo Imaging for Translational Research
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smtheg@ucdavis.edu
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Plant Biology
Lab
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Protein translocation across biological membranes, with a focus on chloroplast membranes. Mechanism of multimeric protein complex assembly. Chloroplast bioenergetics.
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ltian@ucdavis.edu
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Plant Science
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Phytonutrient biochemistry and physiology; Biosynthesis, accumulation and function of carotenoids and polyphenols in plants; Targeted improvement of crop phytonutrient composition and content for enhanced nutritional and medicinal values.
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lintian@ucdavis.edu
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Biochemistry and Molecular Medicine
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The goal of our research is to invent new molecular tools for analyzing and engineering functional neural circuits. We also leverage these tools, combined with optical imaging techniques, to study molecular mechanisms of neurological disorders at system level and to empower searching for novel therapeutic treatments. One of the primary challenges in neuroscience is to link complex neural phenomena to the structure and function of their composite neural circuits. Addressing this problem requires a thorough understanding of patterns of neural activity, and the ability to relate this to physiological processes, behavior and disease states. An essential step towards this goal is the simultaneous recording of neural activity in large, defined populations, ideally in intact circuitry. Traditional electrophysiological approaches provide excellent sensitivity and temporal resolution, but are limited in the number of cells that can be recorded simultaneously.
Fluorescent protein based biosensors can transfer changes in neural state (e.g. membrane potential or essential ion flux or enzyme activity) to fluorescence observables. They are genetically encoded, and can thus be used to label large populations of defined cell types and/or sub-cellular compartments. Combined with modern fluorescence imaging techniques, these probes allow us observe and track how neural networks are established or modified in time and space and find out what goes wrong in diseases. Our lab used a variety of techniques (computational protein engineering, rational design, molecular evolution, chemical synthesis) to develop genetically encoded imaging probes, such as calcium indicators, neurotransmitter sensors and kinase sensors. We also explore strategies for better targeting these sensors to small compartments in the nervous system, such as axon terminals, and for longer expression with reduced cytotoxicity in vivo.
We also integrate our imaging probes to induced pluripotent stem cells (iPSCs)-derived neurons and glias to create a platform for studying psychiatric diseases in vitro. Such cultured human neuronal networks will enable us to visulize how the precise, guided communication in neurons develops, and how it breaks down in diseases. With this system we can test a library of drugs to identify ones that can correct the communications defects in a patient-specific manner; such a drug screening would not be possible on living patients.
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jtrimmer (at) ucdavis (dot) edu
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Neurobiology, Physiology and Behavior
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Cell signaling in mammalian neurons, neuronal cell biology, membrane protein trafficking and function
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rptucker AT ucdavis.edu
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Cell Biology & Human Anatomy
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jlturgeon@ucdavis.edu
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Endocrinology (Internal Med)
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cavandevoort@ucdavis.edu
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Obstetrics & Gynecology - Med
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Primate reproductive physiology, including oocyte maturation, embryonic stem cells and ovarian toxicology.
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andrew.vaughan@ucdmc.ucdavis.edu
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Radiation Oncology
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Cancer Biology
My research interests are centered on mechanisms driving DNA aberration formation. These may lead to both neoplastic changes such as leukemia’s and solid tumors as well as lethal changes that kill the cell. Such alterations are being studied using both molecular biology tools as well as array technology and massively parallel sequencing.
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avazquez@ucdavis.edu
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Otolaryngology - Medicine
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jcvoss@ucdavis.edu
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Biochemistry and Molecular Medicine
Lab
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We are interested in the structure and conformational switching of membrane and lipid binding proteins. Our approach utilizes magnetic resonance of site-directed spin labels to observe protein structure and dynamics. For more information, visit:
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dave@alanine.ucdavis.edu
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Molecular & Cellular Biology
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Structural biology of enzymes and protein-protein interactions. Projects include 1) protein engineering of enzymes involved in a xylose assimilation (XXX) pathway 2) structure- and combinatorial-based drug design targetting apicomplexan parasitic infection and 3) characterizing the structure and function of WD-repeat domains in protein-protein interaction. Our primary research tool is x-ray crystallography but we usually complement this with biochemical and genetic experiments.
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mjwood AT ucdavis DOT edu
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Environmental Toxicology
Lab
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Biochemical & structural mechanisms of environmental gene regulation
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ykxiang@ucdavis.edu
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Pharmacology - Medicine
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The overall goal of my research is to understand cellular and molecular mechanisms on neurohormonal action in heart and brain and the dysregulation of these mechanisms in heart failure and Alzheimer’s disease. We focus on adrenergic receptors (ARs), a family of G-protein coupled receptors (GPCRs). Activation of adrenergic receptor signaling cascades is involved in modulation of cardiovascular function and metabolism during exercise as well as “fight or flight” responses. Adrenergic signaling pathways also regulate memory and learning, pain, emotion, and stress responses in the central nerve system. Dysfunction of receptor signaling pathways are linked to a variety of diseases including heart failure and Alzheimer's disease, and the receptors are the major therapeutic targets in a wide range of clinical conditions. We aim to use integrated approaches that include single molecule analysis, live-cell imaging, and transgenic animals to understand the fundamentals of adrenergic signaling and functions, and its roles in the pathogenesis of heart failure and Alzheimer’s disease. We would like to identify novel therapeutic strategies and targets for drug screening and for treatment of these diseases. Thus far, our studies have provided new insight for treating heart failure and offer a novel therapeutic target for Alzheimer’s disease.
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lfxu@ucdavis.edu
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Microbiology and Molecular Genetics
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Telomeres are the protective nucleoprotein structures at the ends of linear eukaryotic chromosomes. Telomere dysfunction contributes to cancer progression and aging. Our laboratory employs molecular and cytological approaches to study telomere maintenance in human normal cells and cancer cells.
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syamada@ucdavis.edu
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Biomedical Engineering (Grad)
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Cell adhesion, traction force analysis, cadherin, cytoskeletal dynamics, 3D culture, live-cell imaging
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yoko@ucdavis.edu
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Biomedical Engineering (Grad)
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kzarbalis@ucdavis.edu
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Pathology - Medicine
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minzhao@ucdavis.edu
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cjzhou (AT) ucdavis.edu
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Cell Biology & Human Anatomy
Lab
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We are interested in morphogenetic signaling mechanisms of mammalian organogenesis, stem cells, birth defects/congenital diseases, and regeneration
We study morphogenetic signaling regulation in mammalian development and regeneration. We are primarily interested in tissue/organ morphogenesis that is regulated by several inductive factors such as Wnts. Incorrect activity and timing of morphogenetic signaling during development frequently result in embryonic death or severe birth defects. Currently we are investigating the molecular and cellular mechanisms of several developmental disorders and their prevention strategies using Wnt signaling mutants as the research model. We are also investigating the role of Wnt signaling in tissue/organ-specific stem cells and related regeneration processes to enhance their therapeutic potential.
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kzito (at) ucdavis (dot) edu
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Neurobiology, Physiology and Behavior
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The goal of our research is to understand at the cellular and molecular level how synaptic connections form during development of neural circuits in the mammalian cortex. Most of the excitatory synaptic connections in the cortex occur on dendritic spines, tiny protrusions that extend from the dendritic membrane. Dendritic spines are highly dynamic during development both in vitro and in vivo; periods of high motility coincide with synapse formation. Spine motility, driven by actin dynamics, is thought to allow the postsynaptic neuron to explore and sample presynaptic partners. In addition, alterations of spine dynamics and stability have been observed in response to sensory experience, leading to the hypothesis that these anatomical changes underlie the adaptive remodeling of cortical circuits. The identification and characterization of the molecules and mechanisms that control spine morphogenesis will be a crucial step toward understanding the formation and plasticity of cortical circuits. Our approach to this problem combines time-lapse imaging to observe nascent spine formation, and fluorescence recovery after photobleaching (FRAP) to measure protein dynamics, with molecular manipulations of synaptic proteins to decipher their roles in the growth of dendritic spines and synapses. In addition, we use physiological measurements in combination with two-photon uncaging of glutamate to examine the function of nascent synapses at the single synapse level.
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