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2008 Amgen Faculty

Below is the final list of participating faculty in the University of Washington 2008 Amgen Scholars Summer Program. Click on the names below to learn more.

Paul Amieux - Pharmacology

Website: http://depts.washington.edu/phcol/faculty/amieux.php

Description: Our lab uses mouse molecular genetic techniques to analyze the in vivo physiological functions of the enzyme known as the cyclic AMP-Dependent Protein Kinase (PKA). One major focus of our lab is obesity and body-weight regulation. The international epidemic of obesity and the array of co-morbid conditions that accompany obesity (diabetes, cardiovascular disease, certain type of cancer) has provided strong motivation for conducting research on the fundamental mechanisms underlying the obese phenotype. Our lab has created a mutation in one of the regulatory subunits of PKA (called RII beta) that results in mice that are lean and hyperactive and demonstrate resistance to high fat diet induced weight gain and protection from diabetes. We have now taken advantage of bacteriophage (Cre recombinase) and yeast (FLP recombinase) recombinase enzymes to reintroduce this regulatory subunit in particular locations and neuron populations in the brain responsible for body-weight regulation (the arcuate,lateral and ventromedial hypothalamus). Our goal is to refine our understanding of the underlying neural circuitry that governs food intake and metabolism. We also hope to develop an understanding of how key metabolic hormones involved in body-weight regulation use second messenger systems (like the cyclic AMP-PKA system)to modify the electrical and neurochemical activity of neurons involved in regulated appetite and metabolic rate.

Requirements: It would be helpful if the person had some lab experience in biomedical science, but not essential.

James Bassuk - Program in Human Urothelial Biology

Website: http://www.bassuklab.org/

The proliferation of urothelial cells of the lower urinary tract are controlled by positive and negative regulators. One example of a negative regulator is the matricellular protein SPARC, which is found in cell nuclei during cell quiescence in a form that is bound to DNA. One example of a positive regulator is the paracrine growth factor FGF-10, which is found in cell nuclei when the cell is actively synthesizing DNA and progressing through the cell cycle.

One goal of this project is to identify which genes SPARC binds to and to determine the extent that such genic interaction is relevant to the overall process of shutting down the urothelial cell cycle.

Another goal of this project is to identify which genes FGF-10 binds to and to determine if such genic interaction is what triggers renewed DNA synthesis and progression through the urothelial cell cycle.

Data obtained from this project will provide a state-of-the art training vehicle to Amgen Scholars and lead to a better understanding of how urothelial cell proliferation is regulated in health and disease.

Requirements: The opportunity in my lab requires working knowledge of use of antibodies in western and immunoprecipitations, how secondary antibodies work, use of imaging equipment, and gel electrophoresis of nucleic acids.

James Bryers - Bioengineering

Website: http://depts.washington.edu/bioe/people/core/bryers/bryers.html

Description: Biofilms cause a significant amount of all human microbial infections, according to the Centers for Disease Control and Prevention. Nosocomial infections are the fourth leading cause of death in the U.S. with >2 million cases annually (or ~10% of American hospital patients). About 60-70% of all such infections are associated with an implanted medical device causing >$4.5 billion medical costs in 2002 and ~99 , 000 deaths annually. Well-recognized infections involving biofilms include bacterial endocarditis, cystic fibrosis lung infections, deep wound healing, the current dental caries epidemic, vaginosis, urinary tract infections, chronic middle ear infections, and periodontal disease.

Traditional treatment of medical-device based biofilm infections is based on compounds that kill or inhibit the growth of suspended bacteria. However, “biofilm-bound” bacteria tend to be significantly less responsive to antibiotics and antimicrobial stressors than planktonic organisms of the same species. Consequently, systemic antibiotic treatment of a biomedical device infection inevitably fails and requires removal of the device. Moreover, the risk of antibiotic resistance development is drastically increased.

Our goal is to develop a new non-antibiotic based concept in biomaterials design that will, for the first time, promote a short-term defense and long-term immune response to specific bacterial colonization. For short-term immediate defense, model biomaterials will immediately release upon implantation fusion protein complexes - artificial opsonins - designed to enhance the coupling of pathogenic oral bacteria to monocyte-macrophage (MØ); thus promoting phagocytosis. For long-term protection, the biomaterial will transfect antigen-presenting cells (specifically dendritic cells - DCs) to produce T- and B-cell memory and antibody expression.

Requirements: Preferably Molecular biology, microbiology, and/or biochemistry courses with associated lab experience.

Daniel Chiu - Chemistry, Biophysics, Nanotechnology

Website: https://depts.washington.edu/chiugrp/

Description: Chiu lab is focused on developing new methods for probing complex biological processes at the single-cell and single-molecule level, and on applying these new techniques for addressing pressing biological problems. New methods in development include new microfluidic platforms and advanced microscopy techniques.

Requirements: Have completed at least first year General Chemistry courses.

Valerie Daggett - Bioengineering

Website: http://depts.washington.edu/daglab/

Description: We perform molecular dynamics computer simulations of proteins involved in amyloid diseases. One disease we focus on transmissible spongiform encephalopathie, including mad cow disease. We are working to characterize the conformational/structural changes associated with pathology and in designing therapeutic and diagnostic agents against these diseases based on the computer models.

Trisha N. Davis - Biochemistry

Website: http://faculty.washington.edu/tdavis/

Description: Errors in chromosome segregation lead to aneuploidy, which results in birth defects, cancer or cell death. Accurate chromosome segregation is performed by a large molecular machine called the mitotic spindle. The mitotic spindle contains many smaller machines including the centrosome, the microtubules themselves, the kinetochores where the microtubules attach to the chromosome and a multitude of microtubule motors. The ultimate goal of mitotic spindle assembly is to arrange each chromosome with its sister chromatids attached to opposite poles via microtubule fibers. This ensures that when anaphase occurs, the two sister chromatids are pulled apart and partitioned one into each daughter cell. The kinetochore is a part of the mitotic spindle with a critical task. It attaches the chromsomes to the dynamic microtubule fibers and must do so against ~20 pN of force, much more than is required to drag a chromosome through the cellular milieu. All chromosome segregation depends on this connection. We are studying the kinetochore as a molecular machine. The Amgen Scholar would work with two graduate students who are reconstituting the kinetochore from purified components. The student would learn protein purification and quantitative microscopy techniques and would have their own project as part of this larger endeavor.

Requirements: A biology lab course and introductory biology course would be very helpful. A cell biology or biochemistry course would also be helpful.

Horacio de la Iglesia - Biology

Website: http://depts.washington.edu/hacholab/research.php

Description: Research Interests

Research in our laboratory is guided to understand the neural basis of behavior. Specifically, we are interested in biological timing, which can be studied at different levels of organization, using different approaches and throughout the phylogenetic tree.

Biological timing in mammals

Virtually all living species have biological clocks that generate and control the daily cyclic variations in physiology and behavior, such us rhythms in locomotor activity, temperature and hormonal secretion. In mammals, the master control of these so-called circadian rhythms is exerted by a biological clock located within the suprachiasmatic nucleus (SCN) of the brain. We use behavioral, physiological and molecular techniques in order to understand how the SCN generates and orchestrates this array of circadian rhythms.

Biological timing in intertidal crustaceans

Species of the intertidal zone show behavioral and physiological rhythms synchronized to the tidal cycle. These circatidal rhythms also rely on biological clocks and a second line of research in our laboratory is directed to identify the molecular mechanisms and neural pathways by which these clocks are able to sustain rhythms in decapod crustaceans. For this project we study organisms from a unique community of crustaceans distributed throughout the intertidal habitats of our beloved Pacific Northwest.

Norm Dovichi - Chemistry

Website: http://faculty.washington.edu/dovichi/

Description: This laboratory develops and applies tools for the ultrasensitive characterization of biological molecules and are supported by four NIH grants. These projects include three undergraduates, and it may be best to describe their work, which provides examples of work available to our students. One project is to develop an automated tryptic digestion system on a microscale. This device will be employed as part of an on-line protein characterization system, which will couple the digester with capillary electrophoresis and MALDI mass spectrometry. The undergraduate working on this project is evaluating reaction conditions using a fluorogenic substrate, which requires use of a fluorescent microtiter plate reader. The second project employs capillary electrophoresis and laser-induced fluorescence to characterize protein expression in single breast cancer cells. This project has resulted in one publication for Joan Bleeker, an undergraduate in my group. The third project studies stochastic gene expression in the bacterium D. radiodurans using a wide suite of bioanalytical tools, including flow cytometry, confocal microscopy, and capillary electrophoresis with laser-induced fluorescence. This project has resulted in three publications for Vanessa Palmer, another undergraduate in my lab.

Requirements: A strong background in chemistry or biochemistry.

Stan Fields - Genome Sciences and Medicine

Website: http://depts.washington.edu/sfields/

Description: Ubiquitin is a 76 amino acid protein that is an essential signaling molecule in nearly every pathway in eukaryotic cells. Ubiquitin is attached to other proteins only after it has been activated by a cascade of three proteins known as E1, E2 and E3 enzymes. There are many E3 enzymes (called ubiquitin ligases) and they determine the target substrate specificity of this cascade. E3s are critical enzymes: several human diseases, including types of cancer and Parkinson's disease, are caused by mutation of genes that encode E3 enzymes. The goal of this project is to develop a new technology to enable easy and rapid identification of substrates for ubiquitin ligases, from yeast to man.

One way to systematically identify targets for an E3 would be to mutate the enzyme and to mutate ubiquitin so that only the single mutant E3 would be able to transfer the mutant ubiquitin. However, identifying such a mutant combination would be extremely difficult. Evolution has solved this problem for us, because there are several ubiquitin-like proteins that are attached to substrates using enzymes that are very similar to the ubiquitin E1, E2 and E3s. The student will engineer a yeast ubiquitin E3 to enable it to transfer a human ubiquitin-like protein to its substrates. This project will teach molecular biology techniques along with biochemistry, and if all goes well, identification of peptides by using tandem mass spectrometry. The project aims to solve an important biological problem (the elucidation of enzyme-substrate relationships for E3 enzymes) by developing an innovative new technology.

Requirements: Some basic biology coursework.

Michael Gale - Immunology & Virology

Website: http://depts.washington.edu/immunweb/faculty/profiles/gale.html

Description: The research project is focused on understanding how hepatitis C virus regulates intracellular innate immunity to infection. The project will involve the production HCV protein expresssion constucts and testing them in cultured human liver cells. The project will not involve student handling of infectious material. The work will examine the processes by which HCV suppresses signaling through the cellular RIG-I pathway.

Requirements: Applicant must have taken an undergraduate course in biochemistry and molecular biology. Courses in virology and immunology are highly recommended.

Cecilia Giachelli - Bioengineering

Website: http://depts.washington.edu/bioe/people/core/giachelli/giachelli.html

Description: There are two possible projects:

  1. Mechanisms of Vascular Calcification: Understanding basic cellular and molecular mechanisms controlling inappropriate calcification of tissues and medical devices.
  2. Role of osteopontin in inflammatory disease and response of biomaterials to implantation.

Requirements: Biology, Bioechemistry and Molecular Biology courses are recommended.

Jens Gundlach - Physics

Website: http://www.npl.washington.edu/nanopore/index.htm

Description: We are working on a new and direct technique for sequencing DNA. In this technique, single-stranded DNA molecules are driven through a biological pore where they produce a measurable obstruction of an ionic current that also flows through the pore. In collaboration with a microbiologist we are mutating a naturally occurring pore protein to make it suitable for this sequencing technology.

Terrance Kavanagh - Environmental Health

Website: http://depts.washington.edu/envhlth/faculty.php?Kavanagh_Terrance

Brian Kennedy - Biochemistry, Molecular Biology

Website: http://depts.washington.edu/biowww/faculty/kennedy.html

Description: A major focus in my research group is to understand the mechanisms which control aging. We use yeast, worms and mice as models organisms for aging research and have identified genes which modulate the aging process. In an intensive research program a summer student would be given a project related to one of these aging genes and conduct experiments to determine the function(s) of that gene that important for the control of aging. Dietary restriction is one intervention that results in life span extension in every model organism tested. Many of the genes we study are important to mediate the downstream effects of dietary restriction and understanding the mechanisms by which dietary restriction extends longevity is a primary goal of our aging research.

Lih Y. Lin - Electrical Engineering

Website: http://www.ee.washington.edu/research/photonicslab/

Description:

  1. Sorting DNA without touching: Participate in the DEP-FFF DNA sorting project to separate DNA with different lengths using dielectrophoresis (DEP) field-flow fractionation (FFF).
  2. Moving micro/nano particles with a laser: Participate in the opto-plasmonic tweezers project to characterize trapping and rotation of micro/nano particles using laser induced plasmonic radiation.
  3. Measuring light from the invisible: Characterize the optical properties of 3-dimensionally confined nanocrystals.

Dustin Maly - Biochemistry

Website: http://depts.washington.edu/chem/people/faculty/maly.html

Description: Cells are able to integrate an enormous array of environmental information and convert these signals into complex behaviors such as growth, differentiation, and motility. This relay of extracellular stimuli into a phenotypic response involves the transfer of information through complex signal transduction networks that are precisely regulated, both spatially and temporally. Determining how these signal transduction networks are able to turn simple inputs into complex behavior is one of the greatest challenges in modern biology and will provide valuable insight into the cause and treatment of many diseases such as cancer, diabetes, and inflammation. Our group studies how cells sense and respond to their environment, by developing new biochemical and chemical tools that allow a greater quantitative understanding of cellular signaling than is possible with currently available methods. Using the tools of organic synthesis and protein biochemistry we are generating cell permeable small molecules that allow the activation or inactivation of specific signaling enzymes in living cells. While we are interested in studying the function of a number of protein families that are involved in signaling, our initial efforts are focused on enzymes that mediate intracellular phosphorylation (the protein kinases and phosphatases). These studies focus on three main areas: 1) The location-specific function of kinases and phosphatases. 2) The quantitative characterization of specific intracellular phosphorylation events. 3) The conformational plasticity of signaling enzymes.

The specific project within these areas will depend on your interests and prior research experience.

Requirements: Completion of an introductory organic chemistry course (and any associated laboratory courses).

Alex Merz - Cell Biology

Website: http://faculty.washington.edu/merza/

Description: We are a cell biology research group in the Department of Biochemistry at the University of Washington's School of Medicine. Our goal (and that of many other labs) is to understand the fundamental, evolutionarily conserved mechanisms of membrane organization in eukaryotic cells - ultimately in sufficient detail that this aspect of biology will morph into an engineering discipline. We focus on mechanisms of membrane docking, fusion, and repair in living cells and intact organelles. Technologies that we will use include:

  • microscale device fabrication (patterned surfaces, supported membranes; with the UW Center for Nanotechnology)
  • yeast genetics & high-throughput genomics
  • cell-freee biochemical assays
  • protein biochemistry
  • fluorescence spectroscopy
  • ultrasensitive fluorescence microscopy
  • structural biology: cryo electron microscopy of (with Tamir Gonen's group)

The specific project depends on your experience, interests and goals. Please visit our web site: http://faculty.washington.edu/merza.

Requirements: We strongly prefer undergraduates who have taken at least one year of General Chemistry with laboratory. Biologists, chemists, engineers, and other interested students are encouraged to apply.

Danilo C. Pozzo - Chemical Engineering

Website: http://faculty.washington.edu/dpozzo/

Description: Electrophoresis, the motion of charged particles due to an externally applied electric field, is routinely used to separate biomolecules (e.g. DNA, Proteins) from complex mixtures (e.g. human plasma). Besides its paramount importance in most biological fields, electrophoretic separations are also used in diagnostic applications and in biosensors. This research aims to improve electrophoretic bio-separations through the use of nano-structured materials that have not been traditionally applied in this area. These materials include new surfactants and surfactant mixtures, structured sieving matrices (e.g. micelle crystals) and/or non-traditional electrolytes. We will make use of fundamental principles in colloid and polymer science to correlate the physics of the system to the overall efficiency of the separation. Leading edge electrophoresis techniques (e.g. microfluidics, capillary electrophoresis) will be used in conjunction with in-situ characterization experiments to probe the structure and conformation of biomolecules during the separation. Students working in this project will also be exposed to a wide variety of cutting-edge experimental techniques including scattering methods and spectroscopy.

Requirements: Interested students must have completed all of the basic Chemistry courses as well as Organic Chemistry and Physics. Basic laboratory experience is also essential. Students from Chemical Engineering Departments are especially encouraged to participate.

Suzie Hwang Pun - Bioengineering

Website: http://faculty.washington.edu/spun/

Description: The Pun Lab develops nanoparticles for delivery of genes, siRNA, and molecular imaging agents. Applications for these delivery vehicles include siRNA to the central nervous system, cancer therapy, and tissue engineering. Researchers in our lab learn techniques related to mammalian cell culture, nanoparticle formulation and characterization, and gene transfection assays.

Christine Queitsch - Quantitative Genetics, Biochemistry, Genomics, Plant Biology

Website: http://www.gs.washington.edu/labs/queitsch/

Description: Natural selection acts on phenotypes rather than on genotypes. Our lab is interested in identifying molecular mechanisms that rapidly generate selectable phenotypic variation. One potential mechanism of great interest is highly conserved DNA Tandem Repeats (TR). These can expand and contract rapidly thereby creating shorter or longer proteins or regulatory regions. In yeast and for some human diseases phenotypic consequences of length polymorphisms in these TR have been demonstrated for some genes. We have undertaken a systematic approach to the genome of the plant Arabidopsis thaliana and have identified many such variable TR across 50 genetically divergent Arabidopsis populations and we found correlations to previously identified phenotypes. This summer project encompasses generating transgenic plants with variable repeat lengths in a control background to establish causality of repeat length and phenotype. Work will include plasmid construction, plant transformation, phenotypic analysis, and statistical analysis of phenotypes.

Requirements: Lab experience and/or computational background desirable but not required.

Marilyn Roberts - Microbiology, Public Health, Environmental Health

Website: http://faculty.washington.edu/marilynr/

Description: My laboratory is interested in the mechanisms of bacterial antibiotic resistance, the genes coding for resistance and mobile elements that carry these genes. How these genes spread in bacterial communities and the overlap between human, animal and environmental ecosystems. The current projects include

  1. Characterization of the unique antibiotic resistance genes from in environmental Clostridium perfringens, which produce a toxin that causes life-threatening sepsis, gangrene, food-poisoning diseases in man and animals and are commonly found in the environment, determine whether these bacteria can act as a reservoir for these genes for unrelated bacteria;
  2. Characterization of acquired macrolide resistance genes in Haemophilus influenzae isolates from cystic fibrosis patients and how this has varied over time in the Seattle area;
  3. Characterization of acquired macrolide resistances genes in Neisseria gonorrhoeae, a sexually transmitted pathogen;
  4. Characterization of water isolates from rural Uganda water sources; and
  5. Collaborating on a project to determine if agricultural-related exposures to enteric pathogens for farm workers and their families. The student would work on one or more of these projects.

Alexander Rudensky - Immunology

Website: http://pilgrim.immunol.washington.edu/

Description: Our research is focused on understanding the molecular mechanisms governing the development and function of CD4 T lymphocytes and their role in T cell mediated immunity. CD4 T cells recognize foreign and self protein antigens in the form of relatively short peptide fragments associated with MHC class II molecules displayed on the surface of antigen-presenting cells and play a central role in regulation of adaptive immune responses to infection and the maintenance of tolerance to self.

Requirements: I would like students to have taken an undergraduate immunology class, a class in molecular/cell biology, and a class in genetics. Previous lab experience is a plus.

Hannele Ruohola-Baker - Biochemistry

Website: http://depts.washington.edu/taneli/

Hong Shen - Chemical Engineering

Website: http://www.cheme.washington.edu/people/faculty/shen.htm

Our laboratory focuses on developing technologies to probe and intervene the immune and nervous system.

1. Engineering immune cells for the development of single-cell based biosensors;
2. Developing molecular probes for monitoring chemical reactions of intracellular compartments;
3. Developing modular delivery systems for mediating functions of immune cells and nerve cells.

Jay Shendure - Genome Sciences

Website: http://www.gs.washington.edu/faculty/shendure.htm

Description: A new generation of technologies is poised to reduce the cost of DNA sequencing by over two orders of magnitude. However, the routine sequencing of full human genomes will continue to be prohibitively expensive in the context of studies that require even modest sample sizes. However, it is frequently the case that investigators are interested in identifying germline variation or somatic mutations in a particular subset of the genome. Examples of genomic subsets that are highly relevant in the context of specific studies include: (a) a locus to which a disease phenotype has been mapped (i.e. a contiguous genomic region); and (b) the exons of genes belonging to a specific disease-related pathway (i.e. a large set of short, discontiguous sequences). Such subsets total to megabases in length, raising the question of how they can be efficiently isolated without performing hundreds to thousands of PCR reactions per genome. Our ability to take advantage of the power of next-generation sequencing technologies is markedly impaired by the lack of a corresponding targeting method, analogous to PCR, that is matched to the scale at which the new sequencing platforms will routinely operate. To address this critical need, we are exploring several novel strategies for "genome partitioning". Our goal is to develop these strategies into broadly available methods that enable the selective and uniform amplification of complex, arbitrary subsets of a mammalian genome in a single reaction.

Working with a post-doctoral fellow or graduate student in the lab, specific projects on which an Amgen Scholar might participate include: (1) development of an enzymatic method for the uniform amplification of large sets of exon sequences from a human genome; (2) development a hybridization-based method for the selective amplification of contiguous megabase-scale regions from a human genome; (3) integration of these methods with next-generation sequencing technologies, validating their utility by performing targeted variation discovery in a small number of individuals. Depending on interest and skill, the Scholar's project might include experimental and/or computational work.

Requirements: Course work and lab experience in molecular biology or bioinformatics would be very helpful but is not neccesarily required.

Kristin Swanson - Pathology, Mathematics, Applied Mathematics, Neural Pathology

Website: http://www.amath.washington.edu/~swanson/

Description: The Swanson research lab is located in the University Medical Center, and focuses on mathematical modeling and the analysis of quantifiable data obtained through medical imaging such as MRI, PET, and CT. With our convenient location in the UMC, we are in a unique position to compare model results and predictions with data obtained from real patients receiving care at the University. Student researchers necessarily learn aspects of neuro anatomy, tumor evolution and biology, medical imaging, computational and data processing methods. Individualized projects are chosen to best meet the student's interests and abilities, while at the same time serving the overarching goals of the lab.

The lab's current focus includes, but is not limited to, the modeling of brain tumor growth, evolution and response to therapy, and comparisons of information obtained from superficially disparate imaging modalities such as MR and PET. This modeling effort provides many interesting avenues for student research: from data acquisition and processing to investigation and development of new mathematical models of tumor processes.

Our lab is truly interdisciplinary: with over a dozen members with backgrounds ranging from biology to applied mathematics and computer programming, we are able to determine suitable research projects for just about anyone with a scientific background. A vast majority of our lab members are pre-med, providing a stimulating environment with many resources for information and opportunities.

Students are supervised daily by the lab manager, with at least once weekly lab meetings involving progress reports to Dr. Swanson.

Requirements: The student should be have a strong interest and background in either mathematics or medical imaging, and be in good academic standing. Student should have intermediate to advanced computer experience and be comfortable spending extended periods of time at a computer. A background in mathematics including a full calculus sequence, differential equations and linear algebra, and/or experience with computer programming in any form is a plus, although not necessary.