Download Description of Potential Projects for Research Semester, Fall 2014

Potential Faculty Mentors, Project Titles and Descriptions for Research Semester 2014
Faculty Mentor
Ahn, Changwoo
Associate Professor
Department of Environmental
Science and Policy
Ascoli, Giorgio
Professor,
Molecular Neuroscience,
Krasnow Institute for Advanced
Study
Baranova, Ancha
Associate Professor,
School of Systems Biology;
Director, Study of Chronic
Metabolic Diseases
and
Birerdinc, Aybike
Research Assistant Professor,
School of Systems Biology;
Assistant Director, Study of
Chronic Metabolic Diseases
Blackwell, Kim L. (Avrama)
Professor,
Molecular Neuroscience,
Krasnow Institute for Advanced
Study
Cox, Daniel
Associate Professor
and Graduate Program Director,
School of Systems Biology and
Krasnow Institute for Advanced
Study
Title of Project and project number
1. Effects of Plant Diversity on Soil Quality Development in
Mesocosm Wetlands
2. Soil Bacterial Community Patterns
3. Hippocampome Project
Contact Information
Changwoo Ahn
[email protected]
Giorgio Ascoli
[email protected]
4. NeuroMorpho.Org
5. Molecular Pathways Involved in the Pathogenesis of NonAlcoholic Fatty Liver Disease and Other Obesity Related
Pathologies
6. Candidate genes in esophageal cancer: Novel Human Tumor
Suppressor Gene Candidates Identified by Exome Sequencing
Baranova, Ancha
[email protected]
Birerdinc, Aybike
[email protected]
7. The Development of In Vitro System for Migraine Studies
NB: Research site - Inova
Hospital on Gallows
Road
8A. and 8B.
Signaling pathways involved in striatal synaptic plasticity
Avrama Blackwell
[email protected]
9. Transcriptional and Cytoskeletal Control Mechanisms of
Dendrite Development
Daniel N Cox
[email protected]
10. Epigenetic Regulation Via MicroRNAs of Class Specific
Dendrite Morphogenesis
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de Mutsert, Kim
Assistant Professor,
Department of Environmental
Science & Policy
Dumas, Theodore
Assistant Professor of Molecular
Neuroscience,
Krasnow Institute for Advanced
Study
11. Genetic Analysis of Pain Sensation in Response to Noxious
Cold Stimuli
12. Fish diets and food webs in tidal freshwater ecosystems
13. The larval fish community composition of tidal freshwater
ecosystems
14. Pharmacological Ignition of Hippocampal Function In
Juvenile Rats
Kim de Mutsert
[email protected]
Theodore C Dumas
[email protected]
15. Synaptic and Cognitive Development in NMDA Receptor
Chimeric Mice
16. Neuronal Silencing the Mouse Hippocampus Using the Fly
Allatostatin Receptor
17. Tardigrades and the Survival of Learned Information in a
Cryogenic Regime (with Dr. Harold Morowitz)
Frankenfeld, Cara
Assistant Professor,
Global & Community Health,
College of Health & Human
Services
Gallo, Sina
Assistant Professor,
Department of Nutrition and
Food Studies
College of Health and Human
Services
Gillevet, Patrick
Professor,
Department of Environmental
Science and Policy
Director,
MicroBiome Analysis Center
18. Nutrition and Environmental Risk Factors for Human
Health Conditions
Cara Frankenfeld
[email protected]
19. Predictors of Adiposity in Preschool-Aged Children
Sina Gallo
[email protected]
20. Metabiome of Human Disease
Patrick Gillevet
[email protected]
21. Microbial Ecology of Environmental Disease
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Grant, Geraldine M.
Associate Professor,
School of Systems Biology
22. Studies of Idiopathic Pulmonary Fibrosis
A. Over expression of KLF4 in Idiopathic Pulmonary Fibrosis
(IPF)
Geraldine M Grant
[email protected]
B. Localization of KLF4 in Idiopathic Pulmonary Fibrosis (IPF)
by immunohistochemistry.
C. Effect of cytokine exposure on the activation status of a novel
human lung fibroblast population.
D. Investigations for novel surface and secreted markers for
human fibroblasts and myofibroblasts in IPF.
23. Tissue Engineering
Hakami, Ramin
Assistant Professor,
School of Systems Biology
Hamdan, Leila J.
Assistant Professor,
Department of Environmental
Science and Policy
Jafri, Saleet
Professor,
Bioinformatics & Computational
Biology, School of Systems
Biology and Krasnow Institute
for Advanced Study
Jones, R.C.
Professor,
Department of Environmental
Science and Policy
24. Exosome-mediated intercellular communication during
bacterial infections.
Ramin Hakami
[email protected]
25. Host signaling during infection with biodefense bacterial
agents.
26. Microbial ecology of the marine deep biosphere
[email protected]
27. Systems Biology Approaches to Understanding Cardiac
Arrhythmias
Saleet Jafri
[email protected]
28. Water Quality and Aquatic Ecology in The Tidal Potomac
River and its Local Tributaries
R Christian Jones
[email protected]
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Kabbani, Nadine
Assistant Professor,
Molecular Neuroscience,
Krasnow Institute for Advanced
Study
Luther, David
Assistant Professor,
Biology Department
Kehn-Hall, Kylene
Assistant Professor,
National Center for Biodefense
& Infectious Diseases,
School of Systems Biology
29. Axon Growth and Regeneration in the Brain
Nadine Kabbani
[email protected]
30. The Evolution of Acoustic Competition in Songbirds
David Luther
[email protected]
31. Novel Therapeutics for Viral Infections
Kylene Kehn-Hall
[email protected]
Paige, Mikell
Assistant Professor,
Department of Chemistry &
Biochemistry
33. Design and Synthesis of Inhibitors of Protein-Protein
Interactions for the Treatment of Cancers
Peters, Esther
Associate Professor,
Department of Environmental
Science and Policy
Pollack, Anna
Assistant Professor,
Global & Community Health
College of Health & Human
Services
Popov, Serguei
Professor,
Center for Biodefense &
Infectious Disease,
School of Systems Biology
32. Secretome of Viral Infections
Mikell Paige
[email protected]
34. Synthesis and Characterization of a Breast Homing Peptide
Conjugate for the Treatment of Breast Cancer
35. Investigating the Pathobiology of Lung Cancer
36. Using Histology to Understand Interactions between
Organisms and the Environment
Esther Peters
[email protected]
37. Environmental Chemical Exposure and Women’s Health
Anna Pollack
[email protected]
38. Novel Aspect of Anthrax Toxicity: Role of Reactive Oxygen
and Nitrogen Species Generated by Bacterial Cells.
Serguei Popov
[email protected]
39. Nanoparticles for Interrogation of the Infectious Disease
Mechanisms
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Van der Ham, Joris
Adjunct Assistant Professor,
Department of Environmental
Science and Policy
40. Biodiversity of Virginia Spring Seeps
41. Succession of Invertebrate Communities in Potomac
Tributaries
Joris Van der Ham
[email protected]
42. Insects of the George Mason University campus
van Hoek, Monique
Associate Professor,
School of Systems Biology
43. Antimicrobial Peptides
Monique Van Hoek
[email protected]
Willett, James D.
Professor and Director,
School of Systems Biology
Wu, Yuntao
Professor,
School of Systems Biology
45. Exploring Metabolic Changes in Very Old Nematodes
Willett Jim
[email protected]
46. Role of Pyk2 activation in HIV infection
Yuntao Wu
[email protected]
44. Novel Antibiotics
47. Role of Jak/Stat pathway in HIV infection
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Description of Potential Projects for Research Semester, Fall 2014
1. Effects of Plant Diversity on Soil Quality Development in Mesocosm Wetlands
This study investigates the nutrient levels in tissues in wetland plants and calculates the ratios of carbon, nitrogen, and phosphorus, aiming to
test if the ratios can be used as an indicator for predicting productivity of a wetland. The project also involves studying the relationship between
plant diversity and productivity in created wetlands.
2. Soil Bacterial Community Patterns
This study investigates soil bacterial community patterns as affected by initial planting richness in three year old mesocosm wetlands. The
student will conduct DNA extraction from mesocosm soil samples and fingerprint them using T-RFLP, and analyze them by different make-up of
wetland vegetation. There is a potential for the student to be trained in molecular analysis of samples at the USGS, Reston, VA.
3. The Hippocampome Project
In the same vein as a genome, the Hippocampome is envisioned as the ultimate knowledge base describing the structure, activity, and function
of the hippocampus, the brain region responsible for processing conscious autobiographic memories and plans. The foundation of this project is
a catalogue of the many classes of neurons found in the hippocampus and the wiring diagram that interconnects all of them. The descriptions of
these classes are distilled from data published in peer-reviewed journals. Compiling and collating all of this knowledge into a single computerized
resource will uncover new correlations and interrelations that will help discover the cellular mechanisms of hippocampal function and
dysfunction. The student will learn to identify dendritic and axonal morphologies, microscopy techniques for their visualization, how they relate
to the surrounding nervous tissue, and their effect on neuronal activity and network function. See also http://hippocampome.org and
http://krasnow.gmu.edu/cn3
4. NeuroMorpho.Org
NeuroMorpho.Org is a central, one-of-a-kind online neuroscience resource that provides free worldwide access to 3D digital reconstructions of
neurons. Neurons are traced from microscopy imaging in many types of research laboratories, from the study of pharmacology to that of
development. These same data can be reanalyzed for additional discoveries, including computational models of brain function. Data are
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deposited in NeuroMorpho.Org from various species ranging from flies, to rats, to humans, to elephants. Millions of neurons have been
downloaded in more than 100 countries. NeuroMorpho.Org is a leading project in the emerging trend of data sharing in the neuroscience
community that aims to maximize the research potential of collected data. The student will learn to identify dendritic and axonal morphologies,
microscopy techniques for their visualization, how they relate to the surrounding nervous tissue, and their effect on neuronal activity and
network function. See also http://NeuroMorpho.Org
5. Molecular Pathways Involved in the Pathogenesis of Non-Alcoholic Fatty Liver Disease and Other Obesity Related Pathologies
Obesity is the abnormal or excessive increase in adiposity. Lately, obesity has got attention as the state of low grade chronic inflammation
characterized by both macrophage infiltration of AT and increased production of pro-inflammatory cytokines that play a role in insulin resistance
(IR). Non-alcoholic fatty liver disease (NAFLD) is a common disease that comprises a morphological spectrum of liver pathologies ranging from
simple triglyceride accumulation in hepatocytes (fatty liver or hepatic steatosis) to inflammatory conditions (non-alcoholic steatohepatitis;
NASH), eventually leading to fibrosis and cirrhosis.
The major goals of the proposed studies are designed to provide novel insight into the molecular mechanisms by which adipose tissue of obese
individuals promotes the development of secondary complication of obesity.
Techniques: ELISA assays, Bio-Plex assays, qRT-PCR, Cell culture
6. Candidate genes in esophageal cancer: Novel Human Tumor Suppressor Gene Candidates Identified by Exome Sequencing
Eleven NGS exome sequences have been performed on patients with genetic predisposition to esophageal cancer, from the same
region. I have long lists of variations, and I will need a student to analyze these variations for their functional meaning and narrow
down candidate gene lists for further studies. Preliminary work will be performed in the Spring 2014 semester. The Fall student will
pick up where the other student leaves off and proceed with experimental studies of select candidates in a cell-based system.
7. The Development of In Vitro System for Migraine Studies
Migraine is a painful neurological disorder that affects 16% of the general population. Most commonly known triggers include
sensory stimuli (light, smell), stress, changes in sleeping pattern or environment and certain foods. Serum levels of CGRP (Calcitonin
Gene Related Peptide) are elevated in patients during migraine and cluster headaches. The ability of injected CGRP to induce
migraine like headaches and of a CGRP receptor antagonist to provide relief in migraine clinical trials has established the
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involvement of CGRP in migraine. The aim of this/the project is to determine the expression of Cgrp in CA77 cells after exposure to
potential migraine provoking food compounds. The cell line used for research is thyroid C-cell line, CA77 that is derived from
calcitonin secreting endocrine cells of neural crest origin. CA77 cells possess neuronal properties. RT-qPCR will be used to monitor
the CGRP expression to identify the chemicals that affect the development of migraine. This research project would generate and
characterize a valuable model that will eventually help to understand the effect of exposure to various triggering food components
on the pathogenesis of migraine. This research study is focused on the screening of migraine-provoking food compounds. We
expect to quantify expression levels of Cgrp in the CA77 cells before and after exposure to a number of potential migraine provoking
foods and measure the Cgrp expression by using qPCR technique.
8. Signaling Pathways Involved in Striatal Synaptic Plasticity
The striatum is a brain structure that governs habit and skill learning. In addition, Parkinson’s Disease and Huntington’s Disease are
neurodegenerative diseases that involve the striatum. In this structure, the main neurons are the medium spiny projection neurons (MSPNs).
They receive both excitatory inputs from the cerebral cortex, and dopamine inputs. Learning occurs when the cortical inputs and dopamine
inputs are activated with appropriate temporal interval. We are studying the mechanisms that produce the plasticity underlying learning in
striatal neurons.
8A) One project involves behavioral and electrophysiological experiments. The student will train rats to learn that turning in one direction is
rewarded. Early in training this task requires the hippocampus, but later in training, when it has become a habit, the task requires the striatum.
In addition, the student will learn to do electrophysiology, and evaluate the conditions that produce plasticity. Specifically, the student will
investigate the dependence of plasticity on dopamine receptors and also acetylcholine receptors.
8B) A second project involves computer modeling. The student will develop biochemical kinetic models of signaling pathways underlying striatal
synaptic plasticity. Knowledge of calculus and computer programming is advantageous but not required. The student will learn how
experimental design applies to computer simulations.
9. Transcriptional and Cytoskeletal Control Mechanisms of Dendrite Development
The major goals of the proposed studies are designed to provide novel insight into the molecular mechanisms by which transcriptional and
cytoskeletal regulation mediate class-specific dendrite homeostasis. We have identified a broad set of transcription factors that exhibit
differential gene expression among distinct subclasses of neurons via class-specific microarray analyses and have been demonstrated to function
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in the specification of differential dendrite morphology. Specific functional areas of interest that are under transcriptional control include:
autophagy, ribosome biogenesis, and cytoskeletal regulation. This project will afford students the operate to explore one or more of these
questions using novel genetic tools and state-of-the-art cellular imaging techniques. This project likewise offers opportunities for students
interested in genomic analyses and computational modeling/modeling.
Techniques: advanced genetics for temporal and spatial control of gene expression, phenotypic analyses of living neurons in real time, molecular
biology, three-dimensional confocal laser scanning microscopy, and quantitative digital reconstructions of neuronal morphology.
10. Epigenetic Regulation via MicroRNAs of Class Specific Dendrite Morphogenesis
The major goals of the proposed studies seek to investigate the regulatory and epigenetic effect of microRNAs (miRNA) on differential dendrite
morphogenesis within distinct neuronal subtypes. miRNAs play a critical role in post-transcriptional regulation of gene expression within the
genome and we have demonstrated via miRNA microarrays that there is differential expression of miRNAs in different neuron subclasses.
Moreover, through a genome-wide screen we have identified and initially characterized >75 miRNAs that regulate this process. The proposed
project will further explore the effects of of these miRNAs and their regulatory mRNA targets in Drosophila sensory neurons and examine in
living organisms how these miRNAs mechanistically control unique aspects of dendrite development.
Techniques: advanced genetics for temporal and spatial control of gene expression, phenotypic analyses of living neurons in real time, molecular
biology, three-dimensional confocal laser scanning microscopy, and quantitative digital reconstructions of neuronal morphology.
11. Genetic Analysis of Pain Sensation in Response to Noxious Cold Stimuli
Elucidating the cellular and molecular mechanisms that regulate somatosensory signaling is critical in identifying and implementing novel
strategies for the treatment of pain. Nociception, the process of encoding and transmitting noxious stimuli within the nervous system is
essential for organism survival, however can also manifest as undesirable pain sensation. The proposed studies will explore the cellular and
molecular bases of noxious cold nociception under acute conditions using the fruitfly Drosophila melanogaster as a model system. While select
members of the Transient Receptor Potential family of ion channels have been implicated in noxious thermosensation, our understanding of the
mechanisms and signaling pathways by which these channels function in cold transduction, as well as the identity of cold sensing nociceptors, is
far from complete. Using our newly developed behavioral response assay for noxious cold transduction in Drosophila larvae, we will employ in
vivo genetics and transgenic tools to identify and molecularly characterize cold sensing nociceptors.
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Techniques: advanced genetics for temporal and spatial control of gene expression, phenotypic analyses of living neurons in real time, threedimensional confocal laser scanning microscopy, behavioral assays, high-resolution Ca2+ imaging, and quantitative digital reconstructions of
neuronal morphology.
12. Fish Diets and Food Webs in Tidal Freshwater Ecosystems
Reconstruct the complex food web of Potomac River tributaries through stomach content analysis. The study will include fieldwork to collect
fish, and lab work during which the diet items will be identified. In combination with stable isotope analysis, this work will help determine if the
association of fish with specific habitats or locations will be reflected in their diet, and what consequences habitat alterations have for Potomac
River food webs.
13. The Larval Fish Community Composition of Tidal Freshwater Ecosystems
This project will aid in the understanding of spawning patterns of fish in freshwater tidal ecosystems. Lab work will include analyzing
ichthyoplankton samples collected in Gunston Cove and Hunting Creek to identify the species and determine abundance. Research questions can
include: what is the seasonal spawning pattern of fish in these environments? What is the community structure and abundance of larval fish in
Gunston Cove and/or Hunting Creek? How does this relate to the abundance and community composition of adult fishes in these environments?
How important is Gunston Cove as larval fish habitat as compared to Hunting Creek? What environmental factors could be responsible for
potential differences?
14. Pharmacological Ignition of Hippocampal Function in Juvenile Rats
Episodic memories are memories of one's personal experience. The hippocampus is the primary brain structure involved in forming episodic
memories. How hippocampal neurons operate to encode episodic memories is presently unclear, but appears to involve activity-dependent
functional alterations at synapses, the communication points between neurons. Interestingly, episodic memories are not formed until late in the
postnatal period across mammalian species, suggesting delayed development of the hippocampus. As such, the developmental emergence of
episodic memory presents a valuable model for understanding the neuronal properties that are critical for memory formation. We have found
that excitatory synapses in the rat hippocampus are weak in their ability to activate postsynaptic neurons until the end of the third postntatal
week. This is the same age at which hippocampal-dependent learning and memory abilities are first observed in this species, suggesting that
insufficient synaptic excitation limits memory formation or retrieval. Drugs that cause excitatory synaptic responses to last longer also increase
postsynaptic activation in juvenile rats. We have delivered the same drugs to behaving animals and examined their ability to learn hippocampaldependent maze tasks. We have preliminary evidence that suggests that prolonging excitatory synaptic responses improves memory in
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juveniles. Current experiments test the impact of prolonged synaptic excitation on synaptic plasticity and network activity patterns during maze
exploration.
15. Synaptic and Cognitive Development in NMDA Receptor Chimeric Mice
Neural network development and information processing in the brain both require synaptic plasticity. As circuits in the mammalian forebrain
mature, synaptic plasticity is adjusted to better suit information processing. Disruption of this process has been implicated in various
neurodevelopmental disorders, including autism spectrum disorders. In the rodent hippocampus, this transition happens late in postnatal
development, culminating in the emergence of hippocampal-dependent learning and memory abilities at the end of the third postnatal week.
This research aims to explore the molecular determinants of the developmental alterations in synaptic plasticity and emergence of cognitive
abilities. Forebrain glutamatergic N-methyl-D-aspartate receptors (NMDARs) exist primarily as quatramers with two NR1 and two NR2 subunits.
Auxiliary NR2 subunits regulate numerous facets of receptor function. Conductance regulating domains exist in the extracellular amino and
transmembrane regions while synaptic targeting and intracellular signaling domains exist in the intracellular carboxy terminus. At hippocampal
Schaffer collateral (SC-CA1) synapses, NMDARs contain predominantly NR2B subunits during early postnatal development and NR2A subunits
after the end of the third postnatal week. As such, the developmental NR2 subunit switch produces numerous changes in NMDAR function.
Interestingly, the shift in NMDAR composition parallels developmental changes in the ability to induce activity-dependent synaptic plasticity and
completion of the shift marks the onset of adult-like spatial navigation. We have generated transgenic mice that express NMDARs with chimeric
NR2 subunits at SC-CA1 synapses, which allows for separation of the NR2-dependent conductance and intracellular signaling properties. We are
currently conducting research the molecular, physiological, and behavioral level to better understand which NMDAR properties are most closely
related to the age-related changes in synaptic plasticity and in learning and memory abilities
16. Neuronal Silencing the Mouse Hippocampus Using the Fly Allatostatin Receptor
Your brain is made up of billions of neurons each having thousands of communication contact sites. As such, the complexity of brain circuitry is
amazing complex. This complexity makes it difficult to draw precise relationships between neuron function and behavior. Traditionally, this has
been attempted with lesion studies to eliminate small regions of the brain prior to maze training. Unfortunately, virtually all lesions procedures
lack the precision to eliminate specific subpopulations of neurons interspersed with other neuron types and are permanent. Recent advances in
genetic tools have produced the ability to functionally silence highly specific subsets of neurons in a reversible manner. This allows for noninvasive circuit analysis in awake behaving mice. One of these methods involves expression of the fly allatostatin receptor (AlstR). When
activated, this receptor maintains neurons in a hyperpolarized state, in essence, functionally removing them from ongoing activity. We are
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examining the impact of AlstR expression and activation in specific sets of hippocampal neurons to better relate their function to specific aspects
of hippocampal-dependent learning and memory abilities.
17. Tardigrades and the Survival of Learned Information in a Cryogenic Regime
Memory refers to the storage of information across time. Historically, information storage in a biological system has been seen as
requiring either a persistent structural or functional change at the cellular level. Whether a memory relies on a structural or
functional alteration in neurons is a difficult question to address in most model systems as one cannot fully separate structure from
function at the cellular and molecular levels. In this regard, tardigrades of the genus hypsibius (water bears) become an important
neuroscience subject. Tardigrades are microscopic multicellular organisms with a nervous system. They are special organisms in that
they can survive absolute zero and a complete vacuum by taking on a "tun" state in which metabolism ceases. Tardigrades can be
used to separate the structural and functional contributions to memory because all neuronal dynamics can be stopped and restarted
during the storage phase. We train tardigrades in chemoaversive or chemoattractive tasks and then dessicate them and store them
at ultracold temperatures. Upon revival, we test them to see if they remember what they learned prior to being freeze dried.
18. Nutrition and Environmental Risk Factors for Human Health Conditions
Epidemiology is the study of the distribution and determinants of disease frequency in human populations and the application of
this study to control health problems. Student/s will analyze existing human data to evaluate nutritional and environmental risk
factors, including phytoestrogens, environmental toxins, or geographic location. Work may involve analyzing nutrient intake from
dietary records, evaluating dietary and environmental biomarkers from existing data, or comparing different methodologies.
Specific diseases and health conditions that student/s may evaluate include obesity, metabolic syndrome, or other chronic health
conditions. Student/s will integrate biology knowledge with the application of epidemiological and biostatistical concepts.
19. Predictors of Adiposity in Preschool-Aged Children
Childhood obesity has tripled among US youth in the last three decades. There are immediate and long term consequences for obese children
including increased risk for developing metabolic and cardiovascular diseases. The critical periods of pregnancy, infancy and early childhood may
be a crucial time for interventions. In particular, behaviors formed during the preschool years have the potential to prevent obesity in the short
term and even into adulthood. The student will work on data that has been collected over the summer 2014 to identify individual and social
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predictors of adiposity in 2-5 year old children attending daycares in Northern Virginia. Particularly, assess the prevalence of overweight/obesity
and describe body composition in this age group. Utilize diet analysis software to assess nutrient intake and compare to national guidelines. Use
advanced statistical modeling techniques to examine the relationship between lifestyle, contextual factors (e.g., parental stress, socio-culturaleconomic factors) and obesity among pre-school aged children.
20. Metabiome of Human Disease
We have been applying a systems biology approach to characterize the Metabiome of these host and microbial communities (microbiome) to
determine which features are associated with the disease state. We define the Metabiome as all the interactions between the host and the
microbiome. The initial thrust is based on Knowledge Discovery to define the correlations between features and disease classes but the ultimate
goal is to develop new hypothesis that can then be tested using traditional hypothesis driven experimental procedures. We are looking at a
number of human diseases that are associated with dysbiosis of the bacteria community in the human gut. These include Alcoholic Liver
disease, Inflammatory Bowel Disease, Autism, and Colon cancer. Students will have the opportunity to work in the wet lab using NexGen
sequencing, metabolomics, and transcriptomics technology and state-of-the-art bionformatics pipelines.
21. Microbial Ecology of Environmental Disease
We have been applying a systems biology approach to characterize microbial communities in the natural environment. These studies involve
characterization of complex microbial commnities and natural environments and looking at metabolic and expression functionality of these
system. We are looking at a number of diseases or conditions that are driven by environmental factors such as Coral Diseases and Lobster Shell
disease. We are also look at bioremediation processes in oil spills and the biogeochemistry of natural cold seeps. Students will have the
opportunity to work in the wet lab using NexGen sequencing, metabolomics, and transcriptomics technology and state-of-the-art bionformatics
pipelines.
22. Studies of idiopathic pulmonary fibrosis
Idiopathic Pulmonary Fibrosis is a fatal interstitial lung disease that kills over 40,000 individuals each year – more than die from
breast cancer. Currently there are not therapies and no cure for this disease and patient survival time post diagnosis is less than 5
years. There are a number of projects currently available in my lab to investigate the potential role of particular proteins in IPF.
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A.
B.
C.
D.
Localization of Krupple like transcription factor 4(KLF4) in Idiopathic Pulmonary Fibrosis (IPF) The exact location of KLF4
within the IPF lung is not known. This project will use immunohistochemistry on IPF and normal fixed tissue slices to
locate KLF4 in this tissue in addition its association with another factor associated with IPF.
Over expression of Krupple like transcription factor 4(KLF4) in Idiopathic Pulmonary Fibrosis (IPF) While we know that KLF4
is over expressed in IPF fibroblast, we do not know what contribution this makes to IPF. This project will involve
overexpressing KLF4 in Normal human lung fibroblasts and documenting the resulting in change in phenotype in these
cells.
Effect of cytokine exposure on the activation status of a novel human lung fibroblast population. Cytokine exposure plays
a major role in the differentiation of human fibroblasts in the wound response – the pathway which is believed to be out
of control in IPF. Transforming growth factor beta – TGFB1 is the most prevalent cytokine expressed in IPF and is capable
of transforming normal fibroblasts into their activated wound repairing myofibroblast phenotype. We have isolated a
novel population of Normal and IPF fibroblasts. The response of these cells to TGFbeta and any other IPF related cytokine
is unknown. This project involves the exposure of these cells to TGFb1, IL1beta, PDGF and TNFalpha.
Investigation for novel surface marker for human fibroblasts and myofibroblasts. Fibroblast biology and investigations are
marred by the lack of a suitable marker for their isolation. At present fibroblasts are isolated by outgrowth from tissue
pieces…a procedure that results in loss of phenotype and dedifferentiation of cells to a “fibroblast-like” phenotype. The
only currently accepted marker for fibroblasts is expression of alpha smooth muscle actin (alpha-SMA) – an internal
marker and of no use in isolation of fibroblasts in mixed cell culture. We have isolated a novel population of fibroblasts by
differential binding from both IPF and normal tissue. In addition, we have carried out extensive genomic analysis. This
project will involve analysis of large genomic data sets to derive a candidate list for common surface markers between
both populations AND exclusive surface markers that may serve as a biomarkers and tools for isolation
23. Tissue Engineering
Tissue engineering is a rapidly expanding area with great potential. In vitro engineering of chondroctyes, the cells responsible for
cartilage is of paramount importance for autologous transplantation – therapy available for those with cartilage defects and injury.
However these cells when grown in the lab – a step required for this treatment, dedifferentiate. The resulting cells are chondrocyte
like, but do not behave exactly as normal chondrocytes would. One gene expression that is lost during growth in the lab is Krupple
like factor 4 (KLF4). This protein has many roles, however its loss in culture suggest its importance for chondrocyte health. This
project involves reintroducing KLF4 by transfection into normal articular chondrocytes and observing the changes that occur in these
cells.
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24. Exosome-mediated intercellular communication during bacterial infections
Exosomes are small membrane bound extracellular vesicles that carry biological macromolecules from the site of production to
target sites either in the microenvironment or at distant sites away from the origin. Recent studies have demonstrated that
exosomes play a significant role in cell-cell signaling, cancer progression, host immune responses, infectious diseases, and even as
carriers of prions, and The role of exosomes during the progression of infection is a subject that has garnered enormous interest in
recent years. The focus of our research is to understand the fundamental mechanisms of how exosomes are involved during
infection with pathogenic bacteria or viruses, including infection with the biodefense agents Yersinia pestis (Yp) and B. pseudomallei
(Bp). We have examined various purification strategies for isolation of CD63+ exosomes released from a human monocytic cell line
infected with Yp, and have performed a comparative analysis of exosomal miRNA profiles between infected and uninfected cells.
Our results have shown that distinct exosomal populations are released from cells and have also demonstrated the enrichment of
specific miRNAs within exosomes obtained from infected cells. Students on this project will perform functional studies of specific
miRNAs that show strong enrichment in exosomes derived from infected cells. During the course of this project students will learn
several main and important microbiology-related techniques, including culturing bacteria, measuring bacterial growth, setting up
infection experiments, tissue culture techniques, protein analysis techniques such as Western blot analysis, cell staining, and
microscopy techniques. In addition, students will learn the techniques for isolation and characterization of exosomes.
25. Host signaling during infection with biodefense bacterial agents.
New drugs with greater potency against bacterial infections are urgently needed in order to combat bacterial infections more
efficiently and to counter naturally occurring and man-made antibiotic resistant strains. One main focus of our research is discovery
of new measures to combat the biodefense agents Y. pestis (Yp) and B. pseudomallei (Bp), two agents for which effective
therapeutic measures are needed. Yp is a model organism for pathogenic gram-negative bacteria and is the etiological agent of the
plague. Yp can cause high mortality rates, especially in pneumonic form. Plague is now categorized as a reemerging disease given the
rise in the number of reported human cases during the past two decades and the reappearance of outbreaks in various countries
after decades of quiescence. Yp is also of great concern given the documented history of its use in biowarfare and the potential for
its use for bioterrorism considering its high lethality and relative ease of production. Similar to Yp, Bp is a gram-negative biodefense
agent. Bp can cause disease in both humans and animals and can infect a wide range of animal species, including mammals, bird,
and shellfish. In humans, Bp causes melioidosis, often characterized by fever, cough, and chest pain in patients that present with the
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active form of the disease. Discovering host signaling pathways of importance that are engaged by dangerous pathogens such as Yp
and Bp could lead to discovery of novel and potentially multiagent therapeutic measures that are immune to development of
antibiotic resistance mechanisms. To address this critical need, students will perform functional studies of host signaling proteins
that are involved during Y. pestis and B. pseudomallei infection, in order to understand the roles that these proteins play during
infection. Only highly attenuated strains of Yp and Bp (approved for BSL-2) will be used. The important host proteins that have been
identified and selected using a novel protein microarray platform called RPMA will be studied for their roles during infection.
Students will learn several main and important microbiology-related techniques, including culturing bacteria, measuring bacterial
growth, setting up infection experiments, tissue culture techniques, protein analysis techniques such as Western blot analysis and
immunoprecipitation, cell staining, and microscopy techniques.
26. Microbial ecology the marine deep biosphere.
The marine deep biosphere (MDB) is the area in the ocean that exceeds 200m water depth. The MDB includes vast tracts of water
and subsurface sediments. Because of its tremendous volume it is estimated that 92% of Earth’s microorganisms are found in the
MDB. This environment is difficult to access, and as a result is poorly understood. However, recent studies demonstrate that the
MDB is highly diverse, and contains microorganisms uniquely suited to live in permanently dark, cold and deep locations. This
project will use existing samples from the MDB to study microbial community composition, biodiversity, function and density.
Molecular and microbiological approaches will be utilized to provide a comparison of microbial communities from various locations
around the world to determine the features that shape microbial communities and their biogeography.
27. Systems Biology Approaches to Understanding Cardiac Arrhythmias
In this project the student will use computer simulation to study how molecular level events lead to cardiac arrhythmias. This multi-scale
approach allows a quantitative study that integrates experimental information as different levels to get a systems perspective on cardiac
arrhythmias. The project will involve interacting closely with experimental scientists. A desire to do computer programming is required.
28. Water Quality and Aquatic Ecology in the Tidal Potomac River and its Local Tributaries
Specific topics available include: water quality monitoring, E. coli monitoring, stream macroinvertebrates and periphyton, river plankton
dynamics, and harmful algal blooms.
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29. Axon Growth and Regeneration in the Brain
Our laboratory studies the molecular mechanisms by which nicotinic acetylcholine receptors (nAChRs) signal and operate in the developing and
adult brain. We are investigating how nAChRs direct neuronal development by examining the role of nAChRs in growing axons and growth
cones. Growth cones are important developmental structures that play a role in neuronal survival and target selection within the developing
brain. We have developed a neuronal culture system to examine the contributions of nAChRs in growth cones of neurons from the
hippocampus and cortex. We are currently investigating the mechanisms driving growth and movement of axons.
30. The Evolution of Acoustic Competition in Songbirds
Just as the ecological theory of niche competition applies to food resources it can apply to other resources. In this project we use
niche competition to assess acoustic signals, bird songs and frog calls, to investigate if they avoid having similar signals at the same
time and location which would reduce competition and improve signal detection. Results of the project will focus on the ecology and
evolution of animal communication and how species interactions can influence animal communication strategies. This project will
also be in conjunction with research from the National Park Service Soundscape division as recordings from Teton National Park will
be used for the project. The student participating in this project will learn to identify a variety of bird songs and frog calls based on
acoustic and visual cues. The student will also become proficient at using Raven a sound analysis program as well as participate in
collaborative statistical techniques and meetings with scientists from the National Park Service. Finally the student will be asked to
participate in writing a scientific paper based on the results of the project.
31. Novel Therapeutics for Viral Infections
Currently there are no therapeutics for Rift Valley Fever Virus (RVFV) or Venezuelan Equine Encephalitis Virus (VEEV). These two viruses are
transmitted by mosquito, emerging infectious diseases and biological threat agents. Students will be assigned compound(s) and will explore
their toxicity and efficacy against VEEV and RVFV. Vaccine strains of the viruses (BSL-2) will be utilized for these studies. Students will learn
techniques such as cell culture, viral infections, plaque assays, q-RT-PCR assays, and cell viability assays.
32. Secretome of Viral Infections
Nanoparticles will be utilized as a way to capture and characterize various antigens that are released from infected cells. Rift Valley Fever Virus
(RVFV) or Venezuelan Equine Encephalitis Virus (VEEV) infected cells will be studied. These two viruses are transmitted by mosquito, emerging
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infectious diseases and biological threat agents. Vaccine strains of the viruses (BSL-2) will be utilized for these studies. Students will be
responsible for standardizing the nanoparticle capture of selected viral antigens and secreted host proteins. Students will learn techniques such
as cell culture, viral infections, western blot analysis, and protein purification. Students will also have the opportunity to assist with mass
spectrometry analysis.
33. Design and Synthesis of Inhibitors of Protein-Protein Interactions for the Treatment of Cancers
Protein-protein interactions are an attractive target for cancer treatment. However, several challenges still exist in designing a small molecule
drug that interrupts protein-protein interactions. Protein-protein interactions usually involve binding at shallow surfaces between the two
proteins. The inherent difficulty to bind a small molecule to a shallow protein pocket limits the ability to design a high affinity drug. Therefore,
we propose to use a multivalency approach to bind multiple shallow surfaces of the protein. Incorporating a bivalent interaction has been shown
to afford an exponential increase in binding affinity for compounds that would normally have very low binding affinity when interacting at one
site of the protein. This strategy will be used to block oncogenic protein-protein interactions with potentials in treating cancer.
34. Synthesis and characterization of a breast homing peptide conjugate for the treatment of breast cancer
Despite the tremendous successes in chemotherapy for treating cancer, chemotherapy is a very harsh treatment option for many patients. This
project involves the synthesis of an organ-specific delivery system to reduce the systemic toxicity of chemotherapeutic agents. The use of a
peptidic system will enable the inclusion of a reporter group that can be used to monitor the effectiveness of the delivery system in real time.
The goal of this project is to show specificity a classic chemotherapeutic agent conjugated to a breast homing peptide in comparison with the
chemotherapeutic agent in the absence of the breast homing peptide.
35. Investigating the Pathobiology of Lung Cancer
Smoking is strongly correlated with lung cancer. However, not all smokers develop lung cancer. The population of smokers that develop COPD
have an increased risk of eventually developing lung cancer. We intend to explore the association of endogenous small molecule metabolites
with the development of lung cancer. This strategy has the potential to provide a diagnostic method for determining lung cancer risk in patients.
36. Using Histology to Understand Interactions between Organisms and the Environment
The study of cells, tissues, organs, and organ systems is critical not only to learn about the physiology and metabolism of an organism, but to
gain knowledge of that organism's relationships with other organisms (e.g., viruses, bacteria, protozans) and the impacts of environmental
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changes that the organism experiences. Alterations in the cells and tissues from exposure to biotic and abiotic stressors can lead to disease,
impairment in the organism’s vital functions, organs, or systems. The GMU Histology Laboratory supports research on non-human diseases,
systematics and taxonomy, physiology, microbiology, molecular biology, or other areas, using light microscopy to learn how changes in structure
affect function. Projects undertaken in the laboratory include microbial diseases of corals, effects of ingested metals in drinking water on rats
and mice, reproduction in local fish species, distinguishing species of invasive gastropods, and digestion in fireworms. The student will learn
histological techniques to mount tissue sections of samples from field or laboratory experiments (either a current lab project or one of their
choice) and basic slide reading skills to gain an appreciation of the power of this field in organismal and environmental research. The student will
also conduct literature research and prepare a short report on their observations.
37. Environmental chemical exposure and women’s health
Environmental epidemiologists are interested in the study of disease in populations of people and how modifiable exposures may influence
population health. Exposure to environmental chemicals within personal care products are widespread and may lead to adverse health effects.
Exposure to chemicals in personal care products, diet and lifestyle factors and are not entirely understood. In particular, the chemicals of
interest include phenols such as: bisphenol A and triclosan, and parabens. These chemicals have chemical structures that enable them to impact
hormonal binding in experimental settings. These chemicals are included in a class of chemicals known as endocrine disruptors, which have
health implications on reproductive health, cancers, and possible links to obesity and diabetes. Their possible health effects in humans are an
ongoing area of research. As people are exposed to multiple chemicals and there are multiple factors that combine to cause disease processes,
it is necessary to implement statistical modeling to appropriately understand the exposure-disease relationship of interest. The student will learn
statistical modeling necessary for epidemiologic research and the project will focus on phenol and paraben chemical exposures, predictors of
exposure (including diet and lifestyle factors) and insulin resistance in a population of premenopausal women. Insulin levels are a risk factor for
metabolic syndrome and diabetes, important public health problems.
38. Novel Aspect of Anthrax Toxicity: Role of Reactive Oxygen and Nitrogen Species Generated by Bacterial Cells
We recently found that B. anthracis is able to release superoxide radical and nitric oxide as toxic species killing the host cells.
You will study the mechanism of the accumulation of toxic species during infection and carry out their identification using biochemical methods
and mass spectroscopy.
39. Nanoparticles for Interrogation of the Infectious Disease Mechanisms
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In collaboration with the GMU’s Center for Applied Proteomics and Molecular Medicine we develop approaches to investigate changes in the
host proteome during infectious process and to deliver specific treatments using of nanoparticles.
You will be involved in one of the aspects of our current research in which we use nanoparticle technology is applied to harvest the proteins of
the lymph, identify the proteins by mass spectroscopy, and to deliver immunomodulating substances to the lymph nodes in the course of
anthrax infection in mice.
40. Biodiversity of Virginia Spring Seeps
Spring seeps are small isolated freshwater springs, typically located in undisturbed forested areas. In these springs a constant flow of
groundwater comes to the surface, which quickly disappears underground again, resulting in a small wetland habitat. These spring seeps are
inhabited by a wide array of invertebrate species, including molluscs, insects, and crustaceans. Because of the unexplored and isolated nature of
spring seeps, the biodiversity of this habitat has yet to be thoroughly investigated. For example, which species occur in spring seeps, or which
environmental variable determines the species richness, are all questions that are open for study.
Students who are interested in exploring the biodiversity of spring seeps will have the opportunity to participate in fieldwork, process and sort
samples, identify invertebrate species, and contribute to our understanding of the spring seep habitat.
41. Succession of Invertebrate Communities in Potomac Tributaries
Over the last decades some tributaries of the Potomac River have experienced great improvements in water quality. These tributaries were once
devoid of vegetation and now harbor vast beds of submerged aquatic vegetation. At the start of the spring season this vegetation is nearly
absent, but grows to large abundances over the summer. During the fall season the vegetation decomposes and disappears. During its
succession, this aquatic vegetation serves as habitat for many fish and invertebrates. If and how the invertebrate community responds to this
vegetative succession is not fully understood.
Students who are interested in exploring the ecological relationship between the succession of submerged aquatic vegetation and invertebrate
communities will have the opportunity to participate in fieldwork, process and sort samples, analyze data, and contribute to our understanding
of the community ecology of Potomac tributaries.
42. Insects of the George Mason University Campus
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Habitat fragmentation plays a determining role in biological community composition. Fragmented habitats consist out of habitat-patches that
differ in size and isolation. According to conventional ecological theory, the size of these patches will have an effect on the biodiversity that
occur in these patches, where larger patches typically have higher levels of biodiversity. Small patches, however, may represent a unique type of
habitat with special ecological functions and may therefore contain an unusual collection of species. The Fairfax campus of George Mason
University represents a collection of fragmented forest patches. Numerous insect species (including beetles, ants, wasps, etc.) inhabit these
forests patches, and presents a great opportunity to test the ecological effects of habitat fragmentation.
Students who are interested in exploring the role of habitat fragmentation on insect communities will have the opportunity to participate in
fieldwork, process and sort samples, analyze data, and contribute to our understanding of the effects of habitat fragmentation. Findings of these
studies may have implications for the sustainability policy of GMU.
43. Antimicrobial Peptides
Antimicrobial peptides are small peptides that act against bacteria. Students will be assigned a peptide and will explore its activity against
various pathogens, including multidrug resistant bacteria. Students will also design rational variants of their peptide in order to improve its
performance characteristics. Skills taught will include (1) bacterial culturing, McFarland standards, CLSI standards. (2) antimicrobial peptide
assays (3) biofilm assays (4) hemolytic assays (5) cytotoxicity assays (6) advanced data analysis (IC50 plots, etc), (7) bioinformatic analysis of
peptide sequence and prediction of structure. This project can accommodate more than one student; each student will study a different
peptide.
44. Novel Antibiotics
Novel antibiotics are critically needed. Students will be assigned candidate compounds which have potential to be antibiotics to explore their
activity against various pathogens, including multidrug resistant bacteria. These may be natural products or chemically synthesized molecules.
Students will also design checkerboard assays to determine synergistic or antagonistic activity. Skills taught will include (1) bacterial culturing,
McFarland standards, CLSI standards. (2) MIC assays (3) biofilm assays (4) cytotoxicity assays (5) advanced data analysis (IC50 plots, etc), (6)
bioinformatic analysis of bacterial genomes to identify possible drug targets (7) advanced literature searches to develop the background of the
antibiotic and its potential mode of action. This project can accommodate more than one student; each student will study a different antibiotic.
45. Exploring Metabolic Changes in Very Old Nematodes
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What happens as late stage robust adults transition into that terminal state preceding death? Do metabolic markers correlate with the
phenotypic changes so characteristic of senescence? Altered locomotion, increased cellular fragility and accumulation of cellular pigmentation
are characteristic of senescence in most animals, including ourselves.
46. Role of Pyk2 Activation in HIV Infection: Consult with Dr. Wu for description
47. Role of Jak/Stat PATHWAY in HIV INFECTION: Consult with Dr. Wu for description
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