Research in the sciences at Gonzaga University covers a wide range of topics at the cutting edge of science, not just in the traditional definitions of the disciplines, but at the interface of biology, chemistry and physics as well. Below you will find short descriptions of the individual research interests and/or available projects in faculty labs. If you are interested in any of these projects, or even if you simply have questions, please contact the faculty member directly.
For more independent research opportunities, check out our neighbors across the river at WSU-Spokane, particularly in the College of Medical Sciences (http://spokane.wsu.edu/admissions/medical-Sciences ) and the College of Pharmacy (http://www.pharmacy.wsu.edu/ ). Please see descriptions of WSU faculty research below.
If your research will make use of the Gonzaga Greenhouse, you will find more information here.
Student Research Positions
Students interested in applying for a research position must check with specific laboratories below to make sure there is an open position.
Not all faculty have open research positions!
If you are still interested in applying, fill out the application on the Undergraduate Research Main page.
Scroll down to view more detailed information for all faculty members, or click on a faculty member’s name to go to that specific laboratory.
Elizabeth Addis: mechanisms of life history control
Kirk Anders: eukaryotic genetics using yeast as a model organism
Julie Beckstead: interactions between invasive plant species and seed pathogens
Mia Bertagnolli: signaling molecules involved in cell adhesion, migration and disease
Carla Bonilla: molecular mechanisms of bacterial stress response
Shawn Bowers: bioinformatics and biodiversity data discovery
(Dr. Bowers is a member of the Computer Science Department, and has research interests with biological implications.)
Bill Ettinger: regulating photosynthetic carbon fixation
Joey Haydock: reproductive partitioning in the cooperatively breeding acorn woodpecker
Hugh Lefcort: predator/prey relations in aquatic snails (Note: Dr. Lefcort accepts summer students only)
Marianne Poxleitner: evolution of cocaine biosynthesis and genetic enhancement of crops
Nancy Staub: salamander evolutionary biology
Brook Swanson: evolution of complex mechanical systems in animals
Steven Whitfield: disease ecology and global amphibian population decline
Dan Chase: organic synthesis of fluorescent molecules
David Cleary: synthesis and characterization of extended inorganic compounds with applications to chemical sensors, batteries, and catalysis
Matt Cremeens: neuropeptides: neuroscience for the organic chemist
Jeff Cronk: enzymatic and structural studies of β-carbonic anhydrase
Greg Gidofalvi: computational chemistry/electronic structure
Kate Hoffmann: cloning and structural characterization of NIS siderophore synthesis enzymes
Eric Ross: stationary phase development for chromatographic analysis of biomembrane interactions
Jennifer Shepherd: rhodoquinone biosynthesis in parasitic helminths
Joanne Smieja: household water treatments
Stephen Warren: synthesis and development of a diagnostic agent for neurodegenerative diseases and type 2 diabetes
Jeff Watson: mechanism of bacterial HMG-CoA reductase, a target for novel antibiotics
Erik Aver: primordial helium abundance
Weihang Chai: cellular and molecular mechanisms behind the growth of cancer cells, especially the mechanism that regulates telomeres
Theodore Chauvin: Male Reproduction/Sperm Maturation
Leventa Kapás: humoral/hormonal regulation of sleep in rodent models
James Krueger: biochemical regulation of sleep
Éva Szentirmai: the links between sleep and metabolism
Jonathan Wisor: neurobiological basis for sleep, biological rhythms, and sleep disorders therapeutics
WSU College of Pharmacy Faculty
My research is broadly focused on physiological and evolutionary ecology, and specifically on the evolution of mechanisms that control life history strategies. I broadly use vertebrates (currently yellow-bellied marmots and painted turtles) as my study systems because they exhibit a wide range of life strategies that frequently diverge from those of traditional model organisms. Taking a holistic approach, my work combines ecological and hormonal measurements in the field with genetic and hormonal analyses in the laboratory.
I have one open position in my lab for Fall 2014. The student working in this position will assist in several marmot and turtle related projects, but will focus on the following project.
Urbanization of yellow-bellied marmots. Spokane is famous for its marmots. Marmots usually do not live in urban areas, although the prevalence of them is increasing. How can some marmots flourish in urban areas, such as Spokane, while others do not? One avenue that we are exploring is that of diet. Preliminary results suggest that while marmot diet remains the same across urban and rural environments, the availability of preferred food varies. To continue this study, we will be looking at the type of food marmots consume via fecal analysis.
I am interested in genes, chromosomes, and genomes: how they contribute to the traits of an organism, how they are transmitted during replication or cell division, and how they can change from generation to generation. My research makes use of two kinds of life forms: bacteriophages and brewer's yeast. Gonzaga students studying bacteriophages have made a number of fascinating discoveries that I am interested in pursuing. One discovery is a pair of nearly identical phages except one phage is missing five genes that are found in the other phage. Interestingly, these phages have different phenotypes, presenting an opportunity for genetic analysis of the genes to discovery their functions. Another discovery is that phages isolated from the same soils, but at different incubation temperatures, turn out to be unrelated. This has profound implications on our understanding of the diversity of the phage populations that exist in nature. Can we do some deep sequencing of the 100s of phages isolated at GU and learn about the diversity? Can we discover why some clusters of phages grow best at 37C and others are best at 25C? With regard to yeast, I am interseted in understanding a phenotype caused by an extra chromosome when the yeast are aneuploid. We have discovered that the presence of the ACT1 gene on the extra chromosome is necessary for the small colony phenotype of the aneuploid cells and we are trying to understand how the extra gene product is leading to the phenotype.
For students who are interested in bacteriophage research, consider applying to participate in BIOL 405L. For more information, see http://goo.gl/rlcl9T. I will not be taking new students in yeast research this semester.
Projects will focus on microbial ecology, plant-pathogen interactions, and invasion biology. I work on an invasive plant, cheatgrass (Bromus tectorum) that has devastated the Intermountain West. My long-term goal is to eliminate this invasive species and provide land managers with tools to restore cheatgrass-infested natural areas to native plant communities. I currently have two ongoing projects.
One project is to learn more about a seed pathogen that kills cheatgrass seeds and is being investigated as a potential biological control. Student-lead projects may include determining whether this pathogen can also kill other related Bromus species and whether strains on a given species are specifically adapted to that host.
The other project is just beginning but is very exciting. There are naturally occurring die-offs of cheatgrass in the Western United States. Nobody knows who is causing these die offs. We want to figure out if pathogens are involved and how to use these organisms to eliminate cheatgrass and facilitate restoration to native plant communities.
The research work will involve basic microbiology skills (aseptic techniques, making various types of agars, isolation of fungus, and inoculation experiments) as well as seed germination experiments and collecting samples in the field. Preference will be given to students who have completed Ecology (BIOL 102 or 206). Please contact Dr. Beckstead, if you have an interest in working on these projects.
Dr. Bertagnolli is not accepting NEW students for Fall 2014.
As a cell biologist, I am interested in signaling pathways involved with cell adhesion and migration, and how alterations in these processes lead to disease. For example, many individuals with colon cancer have mutations in the Adenomatous Polyposis Coli (APC) gene, which affects cell adhesion and migration and ultimately results in tumor formation and metastasis. Patients with diabetes have altered signaling pathways that result in tissue injury. Using cells cultured in the lab, we can manipulate the genetic and/or physical environment of the cells to mimic the conditions they would experience in patients with these conditions and then study specific parts of signaling pathways that are altered by these conditions. Undergraduate students who participate in these projects become independent in the research laboratory and are exposed to basic laboratory skills as well as more advanced techniques such as cell culture and sterile technique, microscopy, gel electrophoresis and Western immunoblotting. Students typically take Cell Biology (BIOL 201) prior to working in my lab.
This project will focus on original experiments designed to study signaling molecules involved in pathways that lead to tissue injury in diabetes. Control epithelial cells grown in culture will be compared to those that are given high levels of glucose, similar to the conditions found in diabetic patients. Cell morphology, growth rate and adhesion will be analyzed under these conditions. In addition, the distribution of signaling molecules thought to be involved in diabetic pathways will be compared. Laboratory techniques used in these experiments include growing cells in culture, microscopy (both light microscopy and fluorescence microscopy), and image analysis. In addition, the student will gain significant experience in experimental design and data analysis, and the opportunity to interact with collaborators at the Providence Medical Research Center in Spokane.
Dr. Bonilla is not accepting NEW students for Fall 2014.
I am fascinated by the ability of bacteria to survive in all kinds of environments. My research focuses on studying the response to environmental changes of the soil bacterium, Bacillus subtilis; that allow it to survive stressful conditions. B. subtilis is the model Gram positive organism because of its ease of genetic manipulation, sequenced genome and conservation with other pathogenic bacterial species. Bacteria, pathogenic and nonpathogenic, live in complex environments and must monitor their surroundings for nutrients, noxious chemicals, predators, etc. They accomplish this by using proteins that sense the environment (sensor proteins) and proteins that enact changes in gene expression (transcription factors) that alter the physiology of the cell to accommodate the changing conditions. I am interested in understanding the proteins involved in this bacterium’s stress responses at a molecular level.
Student projects will include testing the role of these sensor proteins and transcription factors using in vivo assays such as 1) bacterial survival after exposure to stress on solid and liquid media and 2) understanding the role of sensors proteins in biofilm formation, a form of stress response, by assaying mutants for their ability to form biofilms. Other projects are molecular in nature and include 3) measuring gene expression of stress responsive genes using RT-PCR of different mutant B. subtilis strains and 4) biochemical characterization of sensor proteins in the presence of stress signal molecules to identify activating and regulatory step
My research and each project below is focused on developing informatics tools and approaches related to ecology and biodiversity data discovery and integration.
In collaboration with UC Davis and Arizona State University, we are developing approaches for describing and reasoning over alignments between biological and phylogenetic taxonomies. We have developed a set of tools (collectively called Euler) for describing mappings between two taxonomies and then determining whether the result "makes sense" (is consistent) and if so, to compute the resulting taxonomy induced by the alignment. Given this, there is still a need for developing meaningful visualizations of the resulting taxonomies, developing approaches for explaining (and visualizing) why an alignment is inconsistent (as well as why the alignment produced a certain result), benchmarking different algorithms/tools for performing the alignment, and optimizing the underlying alignment algorithms. Other topics for potential student projects include looking at standard taxonomy revision techniques ("splitting" and "lumping") as well as specific properties of phylogenetic trees to enhance the alignment approach.
Another area for student projects concerns automating the development of ontologies for annotating ecological data sets. This work is in collaboration with UC Santa Barbara (NCEAS) through a variety of ongoing informatics projects to support ecology data management. Ontologies provide structured and controlled vocabularies for describing data sets and can be used to improve the precision and recall of data discovery queries. As an earlier pilot project, we developed a set of scripts to automatically extract and analyze relevant terms from a corpus of ecology papers. We would like to further analyze the results and extend the approach to find richer relationships between terms (which can further improve precision and recall). For example, it may be possible to use co-occurrence or other standard information retrieval approaches to discover relationships among terms. Another approach would be to look at external sources that already provide some term relationships (such as GBIF or WordNet) to "seed" relationships and discover new ones. A similar project would be to extend the approach to consider a wider range of information sources, including ecology metadata repositories (such as the KNB).
The research work described above will involve computer programming skills, primarily focused on developing and running basic scripts (in Python or R) to carry out experiments and to implement relevant tasks. It is anticipated that students will learn a variety of new skills as part of each of the above projects. Students will also potentially collaborate with computer science students working on related topics.
The landscape of Spokane County is a blend of urban and non-urban habitats. The species that live here can respond in different ways to urbanization. Our research team focuses on understanding the contrasting response of a weed, Dalmatian toadflax, and its biological control agent, an herbivorous weevil, to Spokane's landscape. In short, the weed is more abundant in urban areas while the weevil is more abundant in non-urban areas, and we are trying to explain why.
During Fall 2013, our research will proceed in two directions. First, we will analyze data collected in the field this past summer. The other direction will be in developing a theoretical model of weevil and toadflax populations that focuses on connecting larger-scale patterns to events in individual habitat patches. Ideally, prospective students should brainstorm some of their own hypothetical explanations for the patterns in weed and weevil abundance, and then visit me in person to discuss how a model might influence their ideas.
Note: Dr. Dunn is joining our Biology Department in Fall 2014.
Cystic fibrosis (CF) is primarily a fatal respiratory desease that results from a mutation in the CF transmembrane conductance regulator gene (CFTR). The most common mutation in the CFTR gene is called F508del. This mutation produces a protein that does not fold into his proper 3D shape and is therefore rapidly destroyed by cells before it can be used. If F508del-CFTR protein could be induced to fold correctly, individuals with CF could potentially be cured because the mutant protein is functional. In the lab, adding the drug VX-809 can stimulate correct F508del-CFTR folding. However, the exact mechanism leading to proper folding is currently not known. A protein X-ray crystal structure (like the ones you have seen in your textbooks) with this drug bound to F508del-CFTR showing how these molecules interact at the atomic level would greatly aid in understanding how this drug facilitates protein folding. So far, no one has obtained a protein crystal structure for the CFTR protein (normal wild-type or mutant).
One method for producing proteins to be used in protein crystallography (such as CFTR) is to genetically engineer yeast to synthesize the protein. A collaborator has successfully expressed several different proteins in yeast. However, the yeast strain used, Pichia pastoris, has a robust endogenous drug transport mechanism that is able to rapidly eliminate drugs such as VX-809 from the yeast. This natural ability of the yeast makes studying the effect of drugs on proteins synthesized by the yeast difficult and cost prohibitive.
The aim of this project is to delete three different genes coding for putative transcription factors (genes that regulate other genes) in Pichia pastoris. The regulatory genes to be deleted are thought to turn on the expression of drug transport proteins made by this yeast to expel drugs from the yeast. After obtaining genetic evidence for gene deletion, functional assays will be carried out to determine the effect of gene deletion on the yeast's ability to transport drugs.
Students in my lab will have the ability to grow and culture yeast, isolate genomic DNA from yeast, and run PCR reactions to confirm gene deletion work done by previous undergraduate students. Research students will also be working to make a double gene knockout yeast strain, and a triple gene knockout yeast strain. Thirdly, students will be conductiong functional assays on the mutant yeast strains to test for effects on drug transport. Finally, students will have the opportunity to help research, plan, and design some of the experiments and methods.
"Students in my lab do not need to have Genetics; I would be happy to have sophomore, junior or senior students. Enthusiasm for research is as important as courses completed."
Contact Dr. Dunn
Several different lines of evidence suggest that changes in calcium concentration in the chloroplast may have a role in regulating photosynthetic carbon fixation (dark reactions). To test this theory, Dr. Ettinger is in the process of measuring the levels of calcium inside different compartments of the plant chloroplast. Many different ion selective electrodes or fluorescent metal binding dyes lack the ability to effectively discriminate between calcium and magnesium ions. The calcium sensitive biolumenescent protein aequorin has been routinely used to measure calcium in biological systems. The protein emits photons in proportion to the calcium activity in solution. A recombinant DNA vector (pMAQ6) has been developed that directs the expression of aequorin in the plant chloroplast stroma. Dr. Ettinger and his students are transforming common wall cress Arabidopsis thaliana with pMAQ6 with the hopes of measuring calcium concentrations in the chloroplast stroma, and is developing other vectors to direct the expression of aequorin and direct its alternate localization to the thylakoid lumen and the plant cytosol. This research requires skills developed in quantitative analysis (CHEM310, or CHEM240), and genetics and evolution (BIOL202) or molecular biology.
My students will be working on our project to measure Ca2+ concentrations in living plant chloroplasts. We are using calcium-sensitive proteins as in-vivo probes of calcium concentrations. One such probe, Aequorin is a bioluminescent protein that luminesces in direct proportion to the amount of calcium present in solution. My collaborator, Carl Johnson, previously created an RBCS:aequorin construct to study calcium concentrations in the chloroplast stroma. Last summer my students modified Dr. Johnson’s vector to create two thylakoid-localized versions of Aequorin; one with an OE23 transit peptide, and the other with an OE17 transit peptide. The OE23:Aequorin and OE17:Aequorin chimeric genes have been successfully transformed into Arabidopsis thaliana plants. We have performed subcellular localization studies on the transgenic plants and have demonstrated that the plant transformed with the OE23:Aequorin construct is expressing Aequorin and localizing the protein to the thylakoid. We need to do further studies to assess the localization of the OE17:Aequorin protein product. Furthermore, many of the localization studies have been performed on Tobacco plants. We greatly desire to create transgenic tobacco plants using our vectors. This would enable us to perform much more comparative studies.
Another Calcium-sensitive protein probe we are working on is YC3.6, which is calcium-sensitive fluorescent protein. We have designed vectors that should express YC3.6 in plant cells and target the protein selectively to the chloroplast stroma using a transit peptide from the small subunit of Rubisco (RBCS), or to the thylakoid lumen using the transit peptides from either OE17 or OE23. The RBCS:YC3.6 construct was recently created and we are attempting to transform Arabidopsis thaliana plants with that construct. My students will also be working on cloning the YC3.6 gene into an E.coli expression vector. Overexpressing YC3.6 in E. coli will allow us to purify significant amounts of YC3.6 to be used in the study of the pH and oxygen sensitivity of the protein.
The general goal of the project has been to explicitly test hypothesis concerning reproductive partitioning in the cooperatively breeding acorn woodpecker, which have been under study at Hastings Natural History Reservation in central coastal California since 1971. What is cooperative breeding and what is reproductive partitioning? Cooperative breeding refers to social species in which the parents as well as other individuals in the social group provide care for offspring (termed alloparental care). Reproductive partitioning refers to distribution of parentage in social groups in which more then one breeder of each sex competes to breed. In most cooperatively breeding birds, social groups only contain a breeding pair and their offspring that do not breed, at least in part due to incest avoidance, so reproductive partitioning is not an issue. Acorn woodpeckers are unusual among cooperatively breeding birds in that social groups can consist of up to seven males that are unrelated to up to three females within a single social group, in addition to their offspring that are also group members. Thus, reproductive partitioning, which can range from egalitarian with each individual obtaining about equal reproductive success to high skew where a single individual of each sex monopolizes breeding, becomes an important component of each individual’s fitness. Several hypotheses have been proposed that make predictions for the amount of skew, based on factors including within sex relatedness, competitive ability and probability of successfully dispersing to another group. The goals off my students have involved collecting parentage information to test a specific one of these hypotheses.
A critical question to understanding the fitness costs and benefits of sociality in acorn woodpeckers is to obtain parentage information on reproductive partitioning within groups that contain at least two potential breeders within a sex. Because group structure varies considerably (number of potential breeders, age structure, genetic relatedness, and genealogical relationship), information on many groups is required to build a complete picture.
Previous work with students from Gonzaga University has produced the development and optimization of microsatellite primers to determine parentage as well as individual genotypes for 800 individuals (on up to 12 loci). My students have worked on relatively small sets of groups that are similar in structure (e.g. 2 potentially cobreeding males and a single female breeder) addressing specific hypotheses. Despite the wealth of data produced thus far, more data is needed, especially in complex social groups (see project 2 below). In addition, I hope to begin development of a new technique that will allow for the determination of mating success among cobreeding males by detection of sperm in the perivitelline layer of eggs (see project 1 below).
Proximate mechanisms of sperm competition and skew. The eventual goal will be to determine potential proximate mechanisms by which skew is maintained and paternity determined by genotyping sperm present on the perivitelline membrane of eggs. The idea behind this relatively new technique is to identify the sperm trapped between the ovum’s perivitelline layers as an allelic record of sperm competition close to the time and place of fertilization. It involves the relatively simple procedures of collecting eggs either prior to or immediately after the start of incubation and removing the perivitelline membrane. The technical hurdles involve eliminating the maternal and/or embryonic DNA attached to the membrane that, due to their higher concentration, can potentially confound PCR amplification of the sperm DNA, and matching the remaining DNA to potential sires. In collaboration with Dr. Bart Kempenaers of the Max Planck Institute, I hope to have a student working on refining this technique and overcoming the technical hurdles mentioned above. In the case of acorn woodpeckers, the application of this technique over the next few years offers the opportunity to infer information about the mating history of females that, because copulations are almost never seen, cannot be obtained observationally. This will be particularly valuable in the following contexts: (a) Is sperm from both males in groups with 2 cobreeder males (and a single breeder female) generally present at fertilization, even though almost two-thirds of nests are sired by a single male? If not, then it would suggest that females copulate with only a single male for each clutch, in which case it is plausible that males could adjust their behavior according to copulatory access (e.g. for degree of effort in feeding nestlings) If sperm from both males is generally present, the question remains as to why one of the males is generally so much more successful at gaining paternity and has implications for breeders not knowing actual paternity; (b) Do sperm present differ between sequential nests involving the same coalition of males? If so, this would suggest that females copulate with a different male for each clutch, offering a mechanistic explanation for the observed switching of paternity between successive clutches; (c) In large, complex groups containing 2 joint-nesting females and/or 4+ cobreeder males this technique will be especially informative, particularly when such coalitions include younger sons that appear not to achieve their fair share of paternity (based on previously collected data). d) Do sperm present differ in sequential nests involving the same coalition of males and breeder females? If so, this would suggest that females are not consistent with what males they copulate with, again offering a mechanistic explanation for the observed switching of paternity between successive clutches.
Reproductive partitioning in complex groups. The other students working in my lab will continue to investigate the patterns of reproductive bias in large male coalitions (one student) and among complex social groups containing joint-nesting females and large male coalitions (a second student). While only 12% of groups between 2004 and 2008 involved 3 or more cobreeder males, 27% of breeder males lived in coalitions of 3 or more and are thus important to estimating the direct and indirect fitness benefits of cobreeding. Similarly only 15% of groups contain joint-nesting females, but 23% of breeder females live in coalitions. Preliminary data from the complex social groups suggest that nests produced by joint-nesting females are more likely to be multiply-sired than nests of single females and that there is no difference in the frequency of multiple paternity between nests with small vs. large coalitions of cobreeder males. Both of these patterns will be addressed in these student projects.
Please note that Dr. Lefcort accepts applications for summer research positions only.
This research comes about due to the threat of high levels of carbon dioxide that humans are releasing. Carbon dioxide in water is converted to carbonic acid. Sea water that is more acidic lowers calcium and aragonite saturation states which make it harder for organisms to calcify their shells and skeletons. Most attention has been directed at marine creatures where a 0.1 increase in ocean water acidity since the industrial revolution has been noted. Although this value appears small, the change has occurred 10 times faster than at any time in the last 50 million years.
While much attention has been given to marine systems, CO2 may also affect freshwater aquatic systems. Lake acidification gained attention during periods of worry in the 1980’s over acid rain but few studies have explored the effects of CO2 on aquatic systems.
My lab studies the ecological and behavioral effects of heavy metal pollution on populations of Physella columbiana and Lymnaea palustris aquatic pulmonate snails. I am looking for two students to explore how atmospheric CO2 increases may affect snail ecology. In partial collaboration with Dr. Cleary (Chemistry), my students and I will bubble CO2 into pond water and then look at the effects of acidic water on snail anti-predatory behavior.
Although most of the work will be in the laboratory the students need to be prepared to work outside to gathering snails from the field.
I currently have two projects underway in my lab. The first is using bacteriophage as a biocontrol to fight Crown Gall disease. The second is a bioinformatics project to finish and annotate the genome of a chloroplast from Erythroxylum coca.
Bacteriophages are viruses that infect and kill bacteria. We are isolating phage specific for the bacteria Agrobacterium tumefaciens, which causes Crown Gall Disease in horticultural crops. Each isolated phage is purified and assessed for its ability to control Crown Gall Disease in Solanum lycropersicum (tomato) and Vitis vinifera (grapes) Effective phage will be used to creat a biological control agent for crop plants to reduce economic losses due to the disease.
The second project uses bioinformatics techniques to evaluate the newly sequenced Erythroxylum coca choroplast. This project began by isolating Erythroxylum chloroplasts and sequencing them via Solexa 454 technology. Thsi sequence was finished via Sanger sequencing and the complete genome annotated using common bioinformatics programs. The genome will be compared to other chloroplast genomes in the Order Malpighiales to identify differences. These differences will be used to create more accurate phylogenies describing the evolutionary relationships of the order.
Salamanders communicate via pheromones. My research focuses on understanding the structure, function, and evolution of pheromone-producing glands. Salamanders are known for their moist glandular skin, yet little is known about which glands actually produce pheromones other than the well-studied courtship glands on the male chin (known as the mental gland). While pheromones from the mental gland have been well studied, little is know about the pheromones that females produce or about the pheromones that males produce from non-mental glands sources. Interestingly, males of some species lack the pheromone-producing mental gland that is supposedly so important for courtship. Do they produce pheromones from other glands? While the mental gland is known to be controlled by androgens, little is known about the control of other glands. Our current projects focus on understanding androgen control of pheromone production in non-mental glands.
Projects for Fall 2014:
Using immunohistochemistry, we will address questions such as
1) Which glands have receptors for androgens?
2) Is there sexual dimorphism in androgenic control of modified granular glands?
3) How does androgen receptor distribution vary between different types of skin glands? Specifically, are the putative courtship glands the only glands with androgen receptors?
The Swanson Lab studies how complex mechanical systems evolve in animals. Specific current projects include: a study of the swimming performance costs of sexually selected male ornamentation in sword-tail fish, a study of the microstructure and impressive material properties in crustaceans, and a study of the effects of heavy metal pollution on fish feeding and swimming performance. Research students are involved in experimental design, data collection (in the field and in the lab), data analysis and presentations.
Amphibian populations on several continents have been decimated by the emerging infectious disease chytridiomycosis, and as a result it has been estimated that more than 100 species of amphibians worldwide may have been driven extinct by declines associated with this disease. Chytridiomycosis is caused by the chytrid fungal pathogen Batrachochytrium dendrobatidis (Bd), which infects skin tissues of adult frogs. Few mitigation strategies exist to prevent these disease-associated extinctions, but in the last few years research has identified symbiotic cutaneous bacteria living on the the skin of frogs that can inhibit the growth of Bd, and these symbiotic bacteria are now viewed as a leading mitigation strategy for preventing further Bd-associated extinctions. I am seeking students that can help to assess inhibition of this fungal pathogen via symbiotic bacteria collected from amphibian populations in Costa Rica. Research for Spring 2014 will likely involve standard microbiological techniques working with fungal and bacterial cultures. The ultimate goal of this research is to develop biocontrol programs via bacterial probiotics that may lead to large-scale conservation solutions to global amphibian declines.
Highly efficient and tunable organic fluorescent molecules are a growing area of chemical interest as there is significant push for their incorporation into a variety of materials applications such as organic light-emitting diodes, molecular and ionic sensors, and stains for biological markers. One notable example is the 4,4-fluoro-4-bora-3a,4a,diaza-s-indacene core, better known as BODIPY. BODIPYs exhibit remarkable qualities such as intense UV-absorbing and emitting capabilities, high quantum yields, and general insensitivity to a variety of chemical environments. However, the main disadvantage associated with BODIPYs is that they typically absorb and emit between 500-530 nm and possess generally low Stokes shifts of 15-20 nm (600-800 cm-1). Strategies to combat this issue typically involve the installation of secondary and tertiary fluorophore units with different absorption and emission wavelengths. While somewhat successful, such molecules are complex and often require long synthetic routes. An alternative solution to this issue involves a desymmetrization of the BODIPY core to create more energetically discrete ground and excited states. This project aims to expand the scope of fluorescent molecules that exhibit optoelectronic properties akin to BODIPYs but with enhanced Stokes shifts and near-infrared emitting capabilities.
Students working on this project will have the opportunity to learn the following techniques: organic and organometallic synthesis, air-free chemical manipulation via a Schlenk line and/or Glovebox, TLC and column chromatography, 1H and 13C NMR spectroscopy, UV-visible spectroscopy, fluorometry, and mass spectrometry.
Students who are interested should contact Dr. Chase.
Click here to download a description of Dr. Cleary's research interests.
Contact Dr. Cleary
Dr. Cremeens will be on sabbatical during the 2014-2015 academic year, and is not accepting new research students until Fall 2015.
Like serotonin, neuropeptides are signaling molecules within the brain and gastrointestinal tract. Problems with signaling often cause health problems. Despite the prevalence of neuropeptides within the brain and their importance, they are often poorly characterized under physiological conditions. Our research aims to provide key structural characteristics of neuropeptides under physiological conditions for the sake of aiding the rational design of therapeutics.
Neuropeptides are found within neural tissue and bind to transmembrane G-protein coupled receptors (GPCRs). A given neuropeptide may interact with multiple receptors, each inducing unique effects within the nervous system. That they function as ligands to GPCRs, despite their often unstructured or only partially structured nature, is impressive. Whether or not the partially structured site displays a recognition motif is an open question. Directly identifying the functionally important characteristics of a given neuropeptide has been difficult because under physiological conditions they are primarily unstructured, which makes it rather challenging to obtain structural information for rationally designing therapeutics.
This research will target neuropeptides where a fundamental structural question relates to the cis-trans isomerization of an amino acid (proline). For example, under physiological conditions, endomorphin structural characteristics are unknown, and cis-trans proline isomerization might play an important role in receptor binding. Site-specific carbon-deuterium (C-D) labeled neuropeptides will be synthesized by solid-phase peptide synthesis and undergo spectroscopic characterization (IR, circular dichroism, and NMR). The insights gained from these studies will help unravel the complex nature of neuropeptide structure and specificity, which would ideally translate into more facile design of highly selective agonists and antagonists.
The carbonic anhydrases (CAs) catalyze a reaction of fundamental biochemical and physiological importance, the interconversion of carbon dioxide and bicarbonate ion
All CAs are zinc-dependent enzymes and a well-established mechanistic paradigm requires the coordination of substrate to the catalytic zinc ion (Zn2+). The structures determined for the b class carbonic anhydrases (β-CAs), common in plants and bacteria, generally fall into two distinct subclasses based on the observed coordination of zinc. One subclass of β-CAs coordinate Zn2+ tetrahedrally with four protein-derived ligands, and in this configuration access of substrate to the zinc coordination sphere is apparently blocked. The ability of substrate to coordinate to zinc is observed in the other structural subclass. The available evidence supports the hypothesis that the blocked configuration, as seen for example in ECCA, a β-CA from Escherichia coli, represents an inactive conformation of the enzyme, and that all such β-CAs can undergo a transition to an active conformation. In addition, a unique, non-catalytic binding mode for the substrate bicarbonate was discovered in ECCA that appears to stabilize the blocked, inactive form of the enzyme and seems to represent a regulatory mechanism.
This project specifically aims to characterize the allosteric bicarbonate site that is likely shared by many eubacterial β-CAs, including a number of pathogens (e.g., Mycobacterium tuberculosis, Salmonella typhimurium). The structural and functional effects of its disruption by targeted mutagenesis are to be investigated by the primary method of X-ray crystallography, supported by kinetic measurements. In view of its potential as a site for therapeutic intervention, the characterization of the allosteric site will be furthered, in collaboration with Stephen Warren and coworkers, by a virtual screen for potential non-substrate ligands and subsequent determination by crystallography of the structures of the binary complexes. Finally, the relationship between allosteric bicarbonate binding and the hypothesized structural transition in ECCA will be probed by testing the effects of mutations designed to shift the conformational equilibrium, The two observed structural subclasses serve as an explicit two-state model for regulation.
This project will be attractive to students with interest in biochemistry, particularly protein structure and enzymology. It integrates a textbook example of an extremely fast enzyme with allosteric regulation of enzyme activity. The project also emphasizes computational methods, including molecular graphics, modeling, and informatic methods of drug discovery.
A second project that is getting underway is a systems biology investigation of the effects of β-CA knockouts or attenuation of enzyme activity on metabolic flux and expression profiles in prokaryotic cells. The substrates of carbonic anhydrase are hubs in a metabolic network, and limitation of the rate of CO2/HCO3- interconversion is likely to have significant effects on a number of cellular systems. Existing methods of metabolic modeling, such as flux balance analysis, will be applied to these systems to predict the effects of loss of CA activity, and eventual comparison with systems data obtained for wild-type and knockout strains. The development of inhibitors, the goal of the first project, will in principle allow titration of CA activity, in order to examine the effects of varying levels of CA activity on the systems properties of the affected cells. This project will be mainly computational and curational in its early stages, and will be blended with experimental data as progress permits.
With recent advances in the computational resources available to chemists, computational methods that describe the motion of the electrons in atoms and molecules (aka electronic structure methods) have become an increasingly useful tool for understanding/interpreting molecular properties as well as the energetics and dynamics of reactions. Nonetheless, to establish electronic structure theory as a truly predictive tool in chemistry, the development of more accurate and cost-effective methods is desirable. Research in our group aims to address this goal on two fronts. Recently, we have been able to reduce the computational cost of existing models (without a significant loss in accuracy) by developing a systematic procedure for the construction of natural orbitals. In conjunction with collaborators at Argonne National Laboratory, we are also actively pursuing the development of the Graphically Contracted Function approach for electronic structure theory; this method, although still in its infancy, has the potential to significantly improve the cost-effectiveness and accuracy of current state-of-the-art computational models.
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Bacterial pathogens must scavenge iron from their host for growth and proliferation during infection. They have evolved several strategies to do this, one being the biosynthesis and excretion of small, high-affinity iron chelators known as siderophores. Two general pathways for siderophore biosynthesis exist: the well-characterized nonribosomal peptide synthetase (NRPS)-dependent pathway and the NRPS-independent siderophore (NIS) pathway, which relies on a different family of understudied and novel synthetases. NIS synthesis enzymes fall into at least four distinct families (A, A’, B, and C,) based on substrate specificity, and are associated with some of the most virulent and persistent bacterial infections (staph, anthrax, plague) We are initially interested in contributing new structural information for this understudied family of enzymes, as the only two examples of structurally characterized NIS synthetases revealed a novel-binding fold and unique enzyme chemistry. Further structural information, both within types A and C, and new structures of types B and A’, as well as clear information about the secondary substrate binding pocket, and higher oligomerization state, are the primary goals for our work.
Since NIS sythetases fall into four types, we have identified a member of each type, and are pursuing structural characterization as well as developing functional assays. Beginning with two identified siderophore synthesis pathways, we will structurally characterize the type A enzyme DesD from Streptomyces coelicolor (a benign soil bacteria which has been the source of a majority of known natural product antibiotics.) We are also studying the vibrioferrin synthesis pathway out of Vibrio haemolyticus (shellfish food poisoning) by studying PvsB (type B) and PvsD (type A) and Francisella tularensis type A’ protein FslA (which causes the veterinary infection of tularensemia).
Currently several projects in the lab have been optimized for overexpression and purification, and we have begun crystallization trials. Future work for the year will include co-crystallization with substrates or substrate mimics, and the development of functional assays to allow us to quantify the behavior in solution. All of these studies are designed to provide novel structure/function information for uncharacterized subtypes of NIS synthetases, which we intend to use to begin a long-term program exploring not only possible therapeutics for bacterial infection, but also to the better understanding of new enzyme chemistries.
Our research involves developing materials and methodologies for chromatographic analysis of adsorption, binding, and partition events at lipid bilayers. Such interactions can, among other things, influence a drug’s activity and toxicity, affect the activity of membrane proteins, and determine the bioaccumulation of environmental chemicals. Furthermore, lipid bilayers are integral components in many biosensing and liposome-based delivery strategies and the characterization of solute adsorption behavior is crucial to the development and application of these technologies.
In general, high performance affinity chromatography (HPAC) techniques seek to relate the retention of a substance on a packed column to the strength of its specific interaction between the stationary and mobile phases of the column. In principle, this approach to characterizing bioaffinity interactions can offer a number of analytical advantages over other techniques; however it does require the establishment of stable and immobilized biological “films” or “layers” on micro-particulate materials to serve as the stationary phases. The lack of such materials has been a significant impediment to the application of HPAC to biomembrane interactions.
Recent work in our lab has produced materials and methods for assembling lipid bilayers on nanometer-scale silica colloids which we are now using to create lipid bilayer-based stationary phases for liquid chromatography. Preliminary results with the materials are very promising, particularly with respect to evaluating weak and moderate affinity interactions such as those between metal ions and ionophore receptors and channels. Low affinity interactions are particularly difficult to analyze by other techniques and thus the development of materials and methodology that can reliably do so may have particularly broad impact in the field.
Ongoing development of the lipid-silica materials and their application in studies of membrane interactions are the current foci of our research. Projects are available that pertain to the biophysical characterization of lipid bilayers supported within porous silica particles, developing thin organic films for the purpose of affecting lipid-particle interactions, assembling and characterizing new capillary chromatography instrumentation configurations with new pumps and detectors, and chromatographically analyzing molecular interactions with lipid bilayers.
Dr. Shepherd is on sabbatical and is not accepting NEW research students in Fall 2014.
Dr. Shepherd’s research seeks to elucidate the biosynthetic pathway of rhodoquinone (RQ, 1 in Figure 1) which will later be used as a target for the development of new anti-parasitic drugs. RQ is an essential electron carrier used in the anaerobic energy metabolism of species such as the parasitic helminths, the free-living nematode Caenorhabditis elegans (C. elegans), and the purple non-sulfur bacterium, Rhodospirillum rubrum (R. rubrum). RQ is not synthesized or used in humans and other mammals with a primarily aerobic energy metabolism. However, RQ is structurally similar to ubiquinone (coenzyme Q or Q, 2 in Figure 1), an important lipid component involved in electron transport in the aerobic respiratory chain, and the biosynthetic pathways of RQ and Q are proposed to be similar. The biosynthesis of Q has been well-characterized in both prokaryotic and eukaryotic species.
It has recently been shown by Dr. Shepherd’s laboratory that catabolism of Q is required for RQ biosynthesis in R. rubrum. A mutant strain (F11) of R. rubrum has also been identified which can synthesize Q, but not RQ, and therefore cannot grow anaerobically. After sequencing the whole genome of F11, and a spontaneous revertant (RF111), we identified a new gene, rquA, which is the first known gene required for RQ biosynthesis. We are currently working on the expression, purification and characterization of the gene product (RquA). Using bioinformatics and RNA sequencing data, we have also identified four new candidate genes that may be involved in RQ biosynthesis in R. rubrum. We are in the process of preparing gene knock-out mutants to determine the necessity of these genes for RQ biosynthesis. In addition, we have begun work with the C. elegans worm model using RNAi gene knock-downs to identify further candidates required in the RQ biosynthetic pathway. Characterization and regulation of unique enzymes in the RQ biosynthetic pathway will provide a novel target for antihelminthic drug discovery.
Figure 1. Schematic representation of potential ways RquA acts in the biosynthesis of RQ. Pathway A represents the methylation of DMeQ to form a pool of Q reserved for the biosynthesis of RQ. Pathway B represents a complex in which RquA acts in conjunction with other enzymes to act as an amidotransferase to substitute Q’s methoxy group with an amino group on RQ
According to the most recent assessment by the World Health Organization, 884 million people around the world lack access to “improved water supply” and more than 2.5 billion lack access to “improved sanitation”. The health consequences of inadequate access to improved water and sanitation include an estimated 4 billion cases of diarrhea and 1.6 million deaths each year, mostly among young children in developing countries. My projects involve the development and optimization of sustainable, household water treatments for the removal of biological pathogens and naturally occurring inorganic contaminants such as arsenic and fluoride.
I am looking for a student to determine whether or not charred cow bone will effectively remove fluoride ions from natural waters.
The world, especially the industrialized world, is facing 2 emerging epidemics. These epidemics will create significant medical needs that will negatively impact health care systems and the economies of the world if a proactive approach is not taken towards new solutions. One of these emerging epidemics is Type 2 Diabetes which is impacting a growing percent of our population. The other epidemic is the result of the steady increase in the average age of the population world wide (which is projected to continue) coupled to the exponential link between increasing age and the incidence of neurodegenerative disease. Biochemical changes in the metabolism of cell types involved in both of these diseases have been noted.
Lactate has been considered a dead-end waste product of anaerobic metabolism since the 1930's. However, new evidence has emerged showing that lactate is an important energy source that is shuttled between cells and throughout the body. Lactate is being shown to play an important role in muscle and brain metabolism, with the associated implications for diseases in which these tissues form an important component. Muscle metabolism and its alteration have large implications in Type 2 Diabetes. Biochemical changes in the metabolism of the heart muscle are also implicated in congestive heart failure.
In brain metabolism, glucose has traditionally been thought to be the exclusive energy source. However, new hypotheses are emerging that the preferred energy substrate for neurons is not glucose but may instead be lactate. This has wide implications for the study of brain function and diseases as monitored by energy usage. For example, in Alzheimer's disease it has been reported that metabolic deficits often precede the appearance of first symptoms. A probe that could monitor the Krebs cycle could give early indication of decrease in neuronal metabolic activity and neuronal death. This could be an invaluable research tool and diagnostic for neurodegenerative diseases including Alzheimer's and Parkinson's disease.
A specific aim of this research is to develop a probe that monitors lactate's function as an energy substrate while minimizing the number of assumptions and measurements needed to account for the other activities of the molecule and its metabolites. The goal is to monitor some of lactate's functions, but not all of them. To this end lactate analogs have been selected and will be synthesized and evaluated based on their potential for being trapped in the Krebs cycle where it is likely that rate and/or amount of accumulation can be correlated to the rate of activity for the cycle, thus providing a diagnostic indicator for many diseases where energy usage is altered. While currently there is no direct way to monitor aerobic metabolism in vivo at the cellular level,these analogs have this potential when developed as Positron Emission Tomography probes. This is timely and critical research that could advance our understanding of the diagnosis and treatment of energy dependent diseases.
I am looking for a motivated independent student to evaluate lactate analogs for their lactate dehydrogenase activity.
The Watson lab studies the enzyme HMG-CoA reductase and its role in the physiology and pathogenesis of the bacterium Burkholderia cenocepacia, an opportunistic lung pathogen that is naturally resistant to most known antibiotics and a major cause of fatality in cystic fibrosis patients. There are many unusual aspects of this enzyme, from its fundamental biochemistry to its evolutionary history, that suggest it may be a highly regulated enzyme in the bacterium and therefore maybe a new target for future antibiotics. We employ protein chemistry, spectroscopy, molecular biology and bioinformatics techniques to understand the molecular mechanisms by which this unusual enzyme performs its function.
Primary projects include: enzyme kinetics, fluorescence spectroscopy and circular dichroism spectroscopy under changing conditions of pH, enzyme concentration and substrate concentration to identify key structural changes in the enzyme; site-directed mutagenesis of potentially key amino acids in the structure and function of the enzyme and characterization of the mutant enzymes; bioinformatics and evolutionary studies of a newly identified class of bacterial HMG-CoA reductases; generation of plasmid vectors for HMGR gene knockouts in Burkholderia cenocepacia. Students typically have completed at least CHEM 331 and BIOL 105-106 before joining the lab, but exceptions can be made.
My research is on the Primordial Helium Abundance. The focus is on determining the amount of helium produced in the very early universe (3 minutes after the Big Bang) by analyzing the spectral emissions of dwarf galaxies.
In addition to an introduction to Astrophysics and Cosmology, the research involves widely applicable skills such as computer programming, statistical analysis, and model evaluation. Beyond an eagerness to learn, no prior experience in any of those areas is required.
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Get more information on the Aver Lab.
For information on research in the Chai lab, please visit her homepage at WSU.
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Successful fertilization of the egg requires sperm capable of motility and possessing the ability to undergo an acrosome-reaction upon contact with the egg; defects in these sperm functions contribute significantly to male infertility. Sperm gain the ability to swim and to fertilize an oocyte during their transit through the epididymis. Epididymal sperm maturation is characterized by changes in both protein and lipid composition of the sperm. The research in my laboratory investigates the molecular function of sperm maturation, with specific focus on how lipid synthesis and maintenance occur. The laboratory employs various molecular biology and biochemical techniques to investigate the maturation process, with hopes of understanding male infertility and possibly finding a contraceptive target.
Chauvin T.R., Xie F., Liu T., Nicora C.D., Yang F., Camp II, D.G., Smith R.D., and Roberts, K. A Systematic Analysis of a Deep Mouse Epididymal Sperm Proteome. Biology of Reproduction 2012; 87:141, 1-8
Chauvin, T.R., Herndon, M.K. and Nilson, J.H. Cold-Shock-Domain Protein A (CSDA) Contributes Post- Transcriptionally to Gonadotropin-Releasing Hormone-Regulated Expression of Egr1 and Indirectly to Lhb. Biology of Reproduction 2011; 86:53, 1-10
Chauvin, T.R. and Griswold, M.D. Identifcation of Regulated Genes in the Murine Epididymis Using Oligonucleotide Microarrays. Biology of Reproduction 2004; 71:560-569.
Chauvin, T.R. and Griswold, M.D. Characterization of the Expression and Regulation of Genes Necessary for myo-Inositol Biosynthesis and Transport in the Seminiferous Epithelium. Biology of Reproduction 2004; 70:744-751.
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We are interested in understanding the relationship between the regulation of sleep and metabolism. We study the role of metabolism- and feeding-related humoral and neuronal signals in the regulation of biological clocks, sleep-wake activity and arousal. Also, we investigate the effects of clocks and sleep, and the impairments thereof, on metabolism, eating and thermoregulation. We use integrative approach, in vivo rodent models, with simultaneous measurements of the amount and intensity of sleep, oxygen uptake, carbon dioxide production, food intake, body temperature, locomotor and wheel running activities supplemented by blood sampling for hormone measurements.
Contact Dr. Kapás
My laboratory is concerned with the biochemical regulation of sleep. We described the somnogenic actions of many cytokines and showed that interleukin-1 (IL1) and tumor necrosis factor (TNF) are involved in physiological sleep regulation. Our second interest deals with sleep and infectious diseases. Bacterial, protozoan, fungal and viral infectious agents greatly alter sleep. In the case of bacteria we worked out the molecular steps responsible. Currently we are focusing our efforts on the mechanisms involved in influenza virus – induced sleep. In this case, viral double-stranded RNA, released from infected cells, seems responsible for initiating the sleep cascade. Very recently we showed that in mice challenged intranasally with influenza virus, the virus is found within hours in the olfactory bulb where it enhances brain production of cytokines. A third interest of my laboratory is with sleep function and the brain organization of sleep. In short, we hypothesized that neuronal assemblies are the organizational level at which sleep is initiated and that local sleep at this level is dependent upon prior activity within the local network. Thus, we showed that extracellular ATP, released by active glia and neurons enhances expression of TNF and IL1 that in turn drive increases in NREMS locally. TNF expression by neurons is enhanced in the somatosensory cortex if afferent input induced by whisker twitching is increased. Further, individual cortical columns such as somatosensory barrels alternate between functional states, one of which is usually associated with organism sleep and that the sleep-like functional state is induced by TNF. In collaboration with Drs. Sandip Roy, (Engineering) and Hans Van Dongen (Sleep and Performance Research Center) this view of sleep is being mathematically modeled.
The focus of my research is how sleep, metabolism and body temperature regulation are related. In the laboratory, we work with laboratory animals, with rats and mice. A student who is interested in this type of research can participate at many levels, from doing surgeries on animals through data collection, to data analysis.
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For information on research in the Wisor lab, please visit his homepage at WSU.
Contact Dr. Wisor
Research at WSU College of Pharmacy
For research with the following faculty send an e-mail to:
Dr. Andrea Lazarus
Assistant Vice President for Research
WSU College of Pharmacy
Name the faculty with whom you are interested in doing research and briefly explain your interest. Also, please cc Dr. Glass.
Mike Gibson, Ph.D: The focus of this laboratory is understanding the pathophysiology of Mendelian disorders of metabolism, and developing novel pre-clinical treatment approaches with translational relevance. His laboratory employes pharmacological, cellular and dietary treatment approaches in disorders such as succinic semialdehyde dehydrogenase deficiency, phenylketonuria, maple syrup urine disease, galactosemia and transaldolase deficiency, a defect of the pentose phosphate pathway. His training is in protein chemistry, molecular and neurobiology, neuropharmacology and genetics, and various analytical methodologies. His laboratory is actively interested in hepatic biology and novel approaches to liver regeneration.
Sue Marsh, Ph.D: This laboratory is focused on understanding how the heart responds to exercise, diabetes and diet. Dr. Marsh's group has examined the role or post-translational modification of proteins in exercise-induced cardioprotection, as well as investigating the cardiac response of the O-GlcNAc pathway to high fat diets and diabetes. The aim is to understand how post-translational modifications of proteins and their regulatory pathways alter gene regulation of proteins that modulate or contribute to the ability of the heart to remodel or grow in response to various interventions.
Mary Paine, Ph.D, RPh: This laboratory is applying a translational research approach, guided by pharmacokinetic and pharmacodynamic modeling and simulation, to address real-world challenges. Specifically, they are developing novel methodologies to evaluate drug-dietary substance and herbal-supplement interactions prospectively. The lab is also advancing the development of promising orally-active antiparasitic agents for treatment of African sleeping sickness.
Grant Trobridge, Ph.D: Research in the lab is focused on developing retroviral vectors for gene therapy and using vectors as tools for cancer research. The student will have the opportunity to choose a project developing safer retroviral vectors, performing bioinformatics to assess the unwanted side-effect of vector genotoxicity, or using vectors to identify cancer genes by mutagenesis and high-throughput sequencing.
Zhenjia Wang, Ph.D: This laboratory is focused on using nanotechnology and super-resolution optical imaging to investigate the trafficking of cellular compartments. They are developing therapeutic nanopatricle carriers that can cross endothelial barriers in vivo to specifically and effectively deliver therapeutics to activated neutrophils in inflammation. They recently developed a novel method to make 100 nm-sized protein nanoparticles that were loaded with fluorescent dyes or small-molecular-weight drugs. Using real-time and multi-color fluorescense intravital microscopy, they observed that only activated neutrophils internalized protein nanoparticles. In contrast, resting neutrophils, monocytes and endothelial cells did not take up the nanoparticles, indicating that protein nanoparticles as drug carriers can be used to effectively treat neutrophil-mediated inflammatory diseases.
Philip Lazarus, Ph.D: The carcinogenic activity of tobacco carcinogens can often depend on the cellular composition/expression/activity of enzymes that are involved in the activation or detoxification of many tobacco carcinogens or the repair of the DNA adducts they induce. The expression and/or activity of these enzymes may be a critical determinant of individual risk for tobacco carcinogen-induced damage. Studies from this laboratory have identified function/expression-altering genetic polymorphisms for a number of these enzymes, and have shown that they may play a role in increased risk for certain cancers. Current studies are focused upon the identification of high-risk genotypes important in risk for other cancers including colon, esophageal and breast cancer, identification of novel chemoprevention agents, and enzyme promoter characterization and induction mechanisms.
David Liu, Ph.D: The focus of this laboratory is to understand the signaling mechanisms that control proliferation and survival of cancer cells. One goal is to understand how ATF5, a bZIP protein of the ATF/CREB family of transcription factors, promotes survival of cancer cells but is dispensable in normal cells. Studies have revealed that survival of cancer cells (including breast, colon, brain, pancreatic, and lung cancers among others), but not non-cancer cells, requires ATF5 function. It was recently shown that the abundance of ATF5 in cancer cells is critically regulated by both caspase-dependent and proteosome-dependent protein degradation processes. It may be possible to exploit this "vlunerability" of cancer cells for their selective elimination.
Gary Meadows, Ph.D., RPh: This laboratory is focused on how chronic alcohol consumption compromises the anti-tumor immunity and on selecting appropriate targets counter the negative effects. They have shown that chronic alcohol consumption compromises CD8+ T cell function. CD8+ T cells are the key players in anti-tumor immunity and in controlling the survival of the tumor-bearing host. The function of CD8+ T cells are regulated by several immune regulatory cells including the myeloid-derived suppressor cells (MDSC), tumor associated macrophage (TAM), regulatory T cells (Treg), NKT cells, and B cells. They also showed that chronic alcohol consumption increases MDSC and NKT cells, decreases B cells, and shifts the NKT cell cytokine profile from Th1 (anti-tumor) to the Th2 (tumor-evasive). Chronic alcohol consumption does not alter TAM or Treg in the tumor-bearing mice. Two potential projects are examining the signaling pathways that are modulated by chronic alcohol consumption and tumor cells to 1) regulate B cell circulation and 2) alter the cytokine profile of NKT cells.
Jiyue Zhu, Ph.D: This laboratory studies the epigenetic and chromatin regulation of the human telomerase reverse transcriptase (hTERT) gene, which plays critical roles in stem cell self-renewal, aging, and cancer. Whereas telomerase mutations causes premature aging, its activation leads to limitless cell proliferation, a hallmark of all cancers. The ongoing projects focus on the identification of epigenetic elements and regulatory proteins involved in telomerase regulation during stem cell differentiation, nuclear reprogramming, and tumorigenesis, using models of normal and cancer cells, adult stem cells, embryonic stem cells, induced pluripotent stem cells (iPSCs), and transgenic mice.
Salah Ahmed, Ph.D: This laboratory studies the mechanisms behind the development of rheumatoid arthritis, a chronic imflammatory joint disorder, by using synovial fibroblasts isolated from patients with rheumatoid arthritis. These patients also tend to develop cardiovascular complications so Dr. Ahmed is investigating the role of pro-inflammatory cytokines and downstream inflammatory mediators in the manifestation of cardiovascular complications. This work has led to the development of potential new anti-inflammatory molecules that will be tested in clinical studies for the treatment of rheumatoid arthritis and other inflammatory autoimmune diseases.
Sayed Daoud, Ph.D: The focus of this laboratory is on translational cancer therapeutics, with an emphasis on using high-throughput genomic and proteomic approaches for biomarker discovery and classification. One area of interest is determining the biological basis for racial disparity in liver cancer outcomes bewteen African-Americans versus Caucasian Americans. At least 32 proteins have been identified that exhibit differential expression between the two races, and four of these proteins have been targeted for further study to shed light on differences in disease progression or treatment response.
Kathryn Meier, Ph.D: This laboratory studies the molecular and cellular aspects of signal transduction, with a focus on the interface between phospholipid metabolism and protein phosphorylation. One area of interest is the role of lysophosphotidic acid (LPA), a ligand for G protein-coupled receptors, as a paracrine mediator of growth and inflammation. Another area of interest is in the role of phospholipase D2 (PLD), a nutrient sensor that regulates the mTOR pathway, in cancer cell signaling. Other interests include proteins involved in adhesion signaling and their regulation by LPA, epidermal growth factor, and other growth factors. The effects of dietary supplements on cellular signal transduction pathways are also an ongoing area of research.
Gregory Poon, Ph.D., RPh: This laboratory is interested in the molecular mechanism of gene activation by the ETS family of transcription factors. ETS transcription factors, in particular PU.1, are evolutionarily-conserved and widely distributed in virtually all animal species, and are involved in a number of critical cellular functions, making them attractive targets for drug discovery. The development of both innate and adaptive immunity requires the time-and-concentration-dependent activity of PU.1, and the deregulation of PU.1 leads to various types of leukemia and severe immune deficiencies. The activity of PU.1 is mediated by binding to sequence-specific DNA binding sites that exhibit substantial variability, and understanding the physical basis for this sequence selectivity is essential to completely understand its molecular mechanism of action. ETS proteins are involved in a large array of physiological and disease processes, including cancer, and understanding the molecular mechanism of PU.1 has broad potential for understanding PU.1 paralogs in humans and orthologs in other animals. Another research area of interest is developing novel targeting and delivery systems to improve the specificity of drugs for cancer cells and suppressing the emergence of drug resistance. Current studies focus on engineering protein-based bioconjugates for targeted intracellular delivery and effector proteins for gene therapy.