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Paul R. Anderson
- Studies of quantum fields in cosmological and black hole spacetimes
Awarded $120,000 for the period 8/1/09 to 7/31/12
Source: National Science Foundation (NSF)
Evidence indicates that, early in its history, the universe expanded or inflated exponentially, and it may be doing so again. Undergraduate and graduate student participants will be trained in numerical and analytical research techniques that will elucidate phenomena ranging from the expansion of the universe to the effects of quantum fields on black holes. If quantum fluctuations destabilize an exponentially expanding universe, predictions of its future and most inflationary scenarios will be affected. If calculations for reheating in some chaotic inflation scenarios are invalidated, then more sophisticated calculations will be necessary. Investigating particle production during and after gravitational collapse will clarify what happens to information about black-hole formation. Finding that zero-temperature black holes do not exist could have important consequences for thermodynamics.
- Studies of Classical and Quantum Effects in Gravity
Awarded $32,198 for the period 4/2/07 to 6/30/08
Current cosmological observations imply that the universe may
have recently begun a second period of exponential expansion. This
project addresses several questions with implications for accepted
theory. First, it will study whether quantum fluctuations
in the density and pressure of matter and radiation might be unstable
during such a period, with serious consequences
for the fate of the universe. The semi-classical approximation
to quantum gravity, at the foundation of most models of inflation,
would be invalid during at least part of this period and would
have to be replaced by some more sophisticated theory.
Second, the project will study whether quantum fluctuations would
be large enough to invalidate the types of calculations that have
previously predicted the amount of particles produced at the end
of inflation in popular chaotic inflationary models. The
amount of particle production determines the temperature to which
the universe reheats after it finishes inflating, which largely
determines its evolution.
Third, the project will develop a new method to compute the
self-force of a particle orbiting a nonrotating black hole and
emitting scalar radiation. If successful, it could be generalized
to the realistic case of a particle orbiting a rotating black hole
and emitting gravitational radiation. One of the primary sources
of gravitational waves for a space-based detector, like LISA,
is a compact object spiraling into a super massive black hole.
Its trajectory is necessary to get the waveform
for the gravitational waves that are emitted and can
be obtained by solving the radiation reaction problem in gravity. To date, the self-force has only been computed in cases of
high symmetry, such as circular orbits or radial infall.
Fourth, the project will investigate the important case of zero
temperature black holes. Due to the Hawking effect, black holes
radiate and can be assigned thermodynamic properties, such as temperature
and entropy. Quantum effects can alter the spacetime geometry
near the event horizon to change its temperature and entropy.If the project finds that zero temperature black holes cannot exist,
results will have important consequences for black hole thermodynamics.
Finally, the project supports undergraduate and graduate student
training in both numerical and analytical research techniques.
- Accelerating Drug Discovery: On-chip selection of DNA-Encoded Chemical Libraries
Awarded $20,000 for the period 7/1/12 to 6/30/14
Source: NanoMedica LLC
- Accelerating Drug Discovery: On-chip selection of DNA-Encoded Chemical
Awarded $100,000 for the period 7/1/12 to 6/30/14
Source: North Carolina Biotechnology Center (NCBC)
This novel, proprietary NextGeneration Sequencing-enhanced drug discovery platform promises to increase throughput of Wake Forest University’s proprietary Lab-on-Bead technology dramatically, while reducing the time required to identify new drug candidates and corresponding labor and material costs. Commercial development targets discovery of new drug leads and diagnostic reagents for treating and managing cancer.
- Cell Mechanics and Protein Mobility during Neoplastic transformation
Awarded: $400,000 for the period 7/15/11 to 6/30/14
Recent reports indicate that cancerous and normal cells have different physical and mechanical properties, but how these properties change for different cancer cells is ambiguous. For example, some researchers report that cancer cells are softer than normal cells, while others report they are stiffer. This project aims to determine whether these cells were at different stages in their progression from normal to cancerous (neoplastic transformation) or different tumor and cell types. Specifically, it will quantify changes in mechanical properties of human mammary endothelial (HME) cells during neoplastic transformation through particle tracking, cell squeezing, and fluorescence recovery after photobleaching (FRAP) of membrane proteins. FRAP will also be used to determine changes in cytoplasmic and nuclear protein mobility. This work will establish how and why the mechanical properties of HME cells change as they progress from normal to cancerous, which may improve cancer diagnosis, treatment, and prognosis.
- with Eugeny Budyain, Physiology
Mathematical modeling of subsecond dopamine fluctuations in rat
Awarded $12,500; $6,250 Reynolda campus, $6,250 Health
Source: WFU Cross-Campus Collaborative Research Fund
The origin and functional significance of phasic dopamine transmission
in an intact mammalian brain is not clearly understood. This project
aims, first, to develop a mathematical model for the patterns of
subsecond dopamine fluctuations in brain areas that are essential
to the circuitry involved in addiction. Second, a micromotor-driven
manipulator with several significant advantages over current manual
manipulators for obtaining data from ambulatory mammals will be
developed. Results will offer critical insights into the neurobiology
underlying drug abuse and inform the development of therapeutic
agents for addicts.
- Optical Torquing and Nanofluidics
Awarded: $49,771 for the period 1/1/05 to 12/31/06
Source: Research Corporation
Research and technology are driving toward smaller
scales in hope of creating faster and more powerful computers,
more sensitive and
accurate environmental and biological sensors, less invasive
medical instruments, and more effective medicines. This project
laser light to trap and to manipulate very small cylindrical
rods or tubes, rotating them and placing them on specially prepared
that will change their electrical properties. Watching
how their rotation changes as they move close to a surface will
surface interactions. The project will also study how the
properties of the surrounding medium (water, dilute solutions
of flexible rods)
change the nanorods’ rotation. This research will
aid novel nanodevice development, lead to a new understanding
flow near surfaces, and stimulate and guide experimental
and computational work by others. Two undergraduates will learn cutting-edge research. The project
will also greatly improve departmental capabilities in single-molecule
research and encourage collaborations between researchers in different
physics areas and at the Medical School.
- PF-DT WOLED Development
Awarded $200,000 for the period 2/11/13 to 7/31/13
Source: CeeLite Technologies, LLC
This project examines the feasibility and commercial impact of the newly developed WFU PF-BT white-emitting homopolymer family; specifically, its performance in two device architectures: field-induced polymer electroluminescent (FIPEL) and white organic light-emitting diodes (WOLEDs).
- Nanotubes in tumor imaging and therapy
Awarded $20,250 for the period 3/1/11 to 2/29/12
Source: NIH/Wake Forest Baptist Health
Wake Forest investigators have developed prototype multifunctional, multiwalled carbon nanotubes that can image and treat tumors simultaneously. They will fabricate nanotubes of different lengths, architectures, and composition to assess their effectiveness in tissue culture and mouse models. The goal is a therapy that can be precisely directed with low nonspecific toxicity, compatible with standard clinical imaging instruments, and easily cleared by the body.
- Purelux Optimization
Awarded $23,543 for the period 9/1/10 to 6/30/11
Source: PureLux, Inc.
The project uses nanotechnology to produce visible light directly rather than by heating a filament or gas. Very thin, lightweight, and energy efficient, the resulting product could serve a wide range of residential, commercial, and military applications.
- Hybrid Organic-Inorganic Composite Solar Cells for Efficient, Low-Cost, Photoelectric Energy Conversion
Awarded $102,500 for the period 9/1/09 to 8/31/10
Source: US Department of Energy (DOE)/University of South Carolina
This project aims to assemble, fabricate, and test organic photovoltaic devices to serve as solar cells.
- Nanocomposite Distal Tips for Guidewires
Awarded $45,000 for the period 9/25/09 to 9/24/10
Source: Cook Medical
Awarded $18,000 for the period 7/1/10 to 7/31/10
Awarded $2,127 for the period 8/1/10 to 8/16/10
Awarded: $22,595 for the period 8/25/10 to 8/26/10
Source: PureLux, Inc.
The project will use nanotechnology to produce visible light directly rather than by heating a filament or gas. Very thin, lightweight, and energy efficient, it could serve a wide range of residential, commercial, and military applications.
Awarded $200,000 for the period 12/31/09 to 3/31/10
Source: FiberCell, Inc.
Wake Forest and New Mexico State University scientists will improve the efficiency of solar cells based on a novel architecture that uses nanotechnology and optical fibers.
- Hybrid Organic-Inorganic Composite Solar Cells for Efficient, Low-Cost, Photoelectric Energy Conversion
Awarded $99,999 for the period 9/1/08 to 8/31/09
- Nanocomposites for energy utilization
Awarded $11,400 for the period 11/16/08 to 11/15/09
Source: Thai Government
- Targeted CNx NAnowire-Drug Complexes for Enhanced Chemotherapeutic Efficacy
Awarded $ for the period 9/1/08 to 9/30/09
Source: Congressionally Directed Medical Research Program
- Conference for Nanomedicine
Awarded $5,000 for the period 11/1/07 to 4/8/08
Source: North Carolina Biotechnology Center (NCBC)
The Focused Workshop in NanoMedicine: Therapeutic Hyperthemia Problems will bring approximately 100 scientists, engineers, medical researchers, and nanopharmaceutical representatives together for a three-day forum. Twelve invited and 24 contributed talks will discuss the development of nanotherapeutics used in hyperthermia treatments of disease and how it might be guided by traditional pharma. To our knowledge, this workshop will be the first nationwide that is designed to understand the integration of therapeutic development and scientific innovation for an entire class of therapeutics.
- MURI: Self-Assembled Soft Optical NIMS
Awarded $115,677 for the period 10/1/09 to 9/30/10
Source: Air Force Office of Scientific Research (AFOSR)/Kent State University
Negative Index Materials (NIMs) promise a wide variety of exciting applications, such as flat, apertureless lenses; “perfect” lenses with subwavelength resolution; novel antennas; new beam-steering devices; sensor protection strategies; novel band-gap materials; and high-density optical storage. They do not occur in nature, but inherent obstacles have been overcome using such structures as split-ring resonators, which have large negative magnetic susceptibility in the frequency range of interest. To avoid scattering, their linear dimensions must be smaller than a wavelength. Great interest is focusing on VIS NIMs, which operate in the visible range of the spectrum, but the difficulty of creating the appropriate resonant structures on the required nanometer lengths has impeded development.
This multidisciplinary team aims to realize NIMs in the VIS-IR range. The materials will consist of oriented dispersions of metallic nanoparticles, forming a liquid crystal phase, in a host matrix that may also be liquid crystalline. They will be created via self-assembly of the nanoparticles with functionalized surfactant/tethers and processed to form large, thick, 3D films. As liquid crystals, these NIMs will be soft and responsive, allowing easy processing and switching.
- Characterization of the Potential Toxicity of Metal Nanoparticles in Marine Ecosystems Using Oysters
Awarded $66,336 for the period 4/05/07 to 3/04/09
Source: Environmental Protection Agency (EPA)/UNC Charlotte
- Targeting the Glycocalyx (capsule/exopolysaccaride) to Reduce
Awarded $39,696 for the period 7/1/06 to 6/30/08
Source: Orthopaedic Research Education Foundation
NANOTECH will collaborate with the WFUHS Department
of Orthopedic Surgery.
- Novel Carbon Nitride (CNW) Conjugates for Breast Cancer
Awarded $91,055 for the period 8/15/06 to 8/14/07
Source: Department of Defense, Congressionally Directed Medical
Research Programs (CDMRP)
Recently, single-walled carbon nanotubes (SWNT) and Ag nanoshells
have been shown effective in photo-ablating cultured cells. In
both cases, penetrating infrared light generates heat in the nano-object
to raise the temperature in surrounding cells. While promising,
the applicability of these approaches to real therapeutics is limited
because, in both cases, high amounts of light are required to initiate
cell death in tissues. Further, these nanocarriers lack specificity
or targeting modalities.
Carbon-based nanoparticles can be chemically modified
to selectively target breast cancer cells, and when coupled to
nanotube variants, the resulting conjugates can be activated
to photo-ablate tumors with an extraordinarily small amount of
This program will test the concept that carbon nitride nanowires
(CNWs), conjugated to Herceptin, a therapy for certain breast
cancers, can selectively target and photo-thermally ablate HER2-positive
breast cancer tissues, using penetrating near-infrared radiation.
Initial results suggest that CNWs are far superior to SWNTs
silver nanoshells due to their metallic nature and aspect ratio.
This unique property of CNWs opens a new therapeutic application
at depths more clinically relevant than the simple subcutaneous
limits of previous approaches and with reduced dermal injury.
They can also carry multiple functionalities, such as contracting
for imaging the target area, which will allow them to be locally
- Assessment of Status and Opportunities in Nanophase Transition
Metal Oxide Coatings for Air Pollution Control and Mitigation
Awarded $15,000 for the period 7/20/06 to 11/21/06
The project will generate a report on the state-of-the-art in
nanoscale photocatalytic coatings based on transition metal oxides.
This analysis of the literature and intellectual property should
answer the following questions:
• What advantages does nanotechnology offer in developing efficient
photocatalysis of pollutants?
• What mechanisms benefit from small size, surface proximity, high
fields, defect exclusion, surface trapping, and extended coherence
of excited states?
• Can nanotechnology enhance cross-sections, separate charges, or
mitigate well-known tendencies toward poisoning of the catalyst
in realistic environments?
• Can we conclude that current engineering technologies for broad
area thin film fabrication are sufficient for practical implementation
of such nanophase materials?
The answers to these questions will identify
both the opportunities and bottlenecks to implementing such technologies
in air pollution
control/mitigation. The project will significantly enhance
knowledge base in this important science field, and the product
will serve the strategic planning process as a screening tool
for future research and future NCER and SBIR solicitations.
- Self-Assembled Soft Optical NIMs
Awarded $115,677 for the period 10/1/06 to 9/30/07
Source: AFOSR, MURI
Negative Index Materials (NIMs) promise a wide variety of
exciting applications, such as flat, apertureless lenses; “perfect” lenses
with subwavelength resolution; novel antennas; new beam-steering
devices; sensor protection strategies; novel band-gap materials;
and high-density optical storage. They do not occur in nature,
but inherent obstacles have been overcome by the use of specially
constructed resonant structures, such as split ring resonators,
that have large negative magnetic susceptibility in the frequency
range of interest. To avoid scattering, their linear dimensions
must be smaller than a wavelength. Their tremendous scientific
and technological potential has generated great interest
in VIS NIMs, which operate in the visible range of the spectrum,
none have been yet realized, due to the difficulty of creating
the appropriate resonant structures on the required nanometer
lengths. The multidisciplinary team aims to realize NIMs in the VIS-IR
range. The materials will consist of oriented dispersions
of metallic nanoparticles, forming a liquid crystal phase,
host matrix that may also be liquid crystalline. They will
be created via self-assembly of the nanoparticles with functionalized
surfactant/tethers and processed to form large, thick,
This strategy will optimize the materials’ response
to competing factors of index magnitude, loss, dispersion,
As liquid crystals, these NIMs will be soft and responsive,
allowing easy processing and switching.
- Charge-Transfer Nanocomposites: The Effects of Scale Hierarchy
Awarded $151,000 for the period 1/1/06 to12/31/06
This research program will first quantify charge-transfer
mechanisms and time scales relevant to nanoparticulite/electro-active
blends (charge-transfer nanocomposites). These features will
be correlated with induced morphological modifications, modifications
to optical absorption cross-sections, and localization effects.
The program will then examine electronic and optical phenomena
associated with degrees of matrix order and disorder, or scale
hierarchy, to determine if nanotube/host interactions are modified
when the nanoparticles are ordered over length scales commensurate
with polarons/excitons or the wavelength of incident light. Finally,
the program will integrate nanotube-based matrix composites into
organic photovoltaic devices and organic optical sensing devices,
such as CCDs (charge-coupled devices), which are used in digital
and video cameras and optical scanners, and photodiodes.
- with Joel Stitzel, Biomedical Engineering,
Development of Electrospinning Apparatus for Tissue Engineering
Awarded $14,700 for the period 5/6/05 to 5/15/06
Source: WFU Cross-Campus Collaborative Research
The team aims to purchase a negative pressure glove
box with an antechamber and to fabricate an electrospinning apparatus
for the development of vascular scaffolds. These vascular scaffolds,
when seeded with endothelial or other appropriate cells, hold promise
as vein and potential organ replacements. The investigators propose
(1) to generate vascular scaffolds from several types of protein
components by electrospinning; (2) to optimize the synthesis of
these scaffolds; and (3) to test the mechanical strength, biocompatibility,
and biochemical characteristics of the synthetic scaffolds compared
to decellularized scaffolds or native vascular vessels.
- Agile Response Coatings
Awarded $1,443,000 for the period 4/1/05 to 3/31/08
For twenty years, US forces have increasingly been required to
respond to asymmetric situational threats, and Air Force technologies
must perform multirole surveillance and tactical tasks. Reliance
on slower, long-term, unmanned platforms with search-and-destroy
capabilities like the Global Hawk system and stealth insertion
using manned vehicles like the F-117 and B-2 demands agile coloration
that can sense ambient thermal and lighting conditions; novel
materials solutions to deterioration in aging and long-term deployed
systems; and the ability to monitor all operational aspects of
vehicle integrity, including structural and air frame components
during flight.The Agile Response Coatings (ARC) program aims to develop a single
coating system that biomimetically responds to its surroundings
and airframe integrity, using sensing and electromagnetic modulation
technologies based on novel nanostructured materials. The program
has four specific task areas:
1. Electromagnetic Modulation.
Novel electrochromic polymers will be coupled with metamaterial
functionalities, agile coloration, and reflective technologies to
respond to ambient thermal, lighting, and threat conditions in real
2. Sensor Embed Technologies. Nano-engineered material
will be used to create novel, high-sensitivity sensor systems with
self-diagnostic functions, including the ability to sense strain,
corrosion, and IR, locally and globally, and pressure transduction.
3. Macro-electronic, distributed connectivity. Organic
macro-electronics will create a networked interconnectivity among
sensors, allowing the coating system to respond autonomously to
a wide variety of stimuli.
4. Tangential functionalities. Several tangential
functionalities will be added to the coating system, including corrosion
retardation and active vibration damping.
The program teams Dr. Carroll with investigators from the University
of Florida and New Mexico State University and corporate partners
Foster Miller, Inc., and International Technology Corporation.
Coordinated through WFU, each site is responsible for developing
and integrating a component into the final coating system. The
“distributed” management structure will enhance synergistic
and shared activities among team members and rapid response to
Samuel Cho (see also COMPUTER SCIENCE)
Extrapolating the concept of protein corona for understanding nanoparticles at large
Awarded $93,491for the period 8/15/12 to 7/31/15
Source: National Science Foundation (NSF)/Clemson University
These studies aim to decipher the basic mechanisms of biocorona formation using molecular dynamics (MD) simulations (Cho lab) validated by experiment (Ke lab). Results will translate well-established theoretical and simulation approaches from protein folding to NanoEHS for great educational, economic, and environmental benefits. The Cho lab develops and performs MD simulations to examine the formation of AgNP-biocoronas at molecular resolution and to define the main determinants, such as time, free energy, and stability. Their GPU-optimized approaches perform 10-100x faster than traditional CPU approaches that preclude simulations at the relevant time and length scales. The Ke lab will validate these calculations experimentally; then additional simulations will guide the design of new NP-biocorona simulations. The Cho lab will also model NP binding interactions with proteins and glucose.
Gregory Brown Cook
- Quasi-equilibrium BH-BH and NS-BH binary Initial Data
Awarded $35,000 for the period 10/8/08 to 10/31/09
The collision of a pair of compact objects, either black holes
or neutron stars, is a dramatic event that gravitational wave observatories,
such as LISA and LIGO, hope soon to detect. The simulations to
be performed in this project, starting from compact binary initial
data, will provide the theoretical foundation for interpreting
much of the data these observatories obtain. This work aims to
improve the techniques and numerical tools for constructing compact
binary initial data, to explore the space of interesting solutions,
and to train undergraduate and graduate students.
Jacquelyn Fetrow (see also Computer Science)
- Analysis of redox-modulated signaling networks in response to ionizing radiation
Awarded $11,209 for the period 3/1/10 to 2/28/13
This project applies advanced systems biology methods to define the consequences of combined kinase mutations in head and neck squamous cell carcinomas (HNSCC). It tests the hypothesis that subsets of kinase mutations, unique to each patient, rewire the signaling pathways that modulate responses to radiation and drug therapies and could point to patient-tailored therapies with higher cure rates and lower toxicity.
- Integrin Function in Cartilage
Awarded $1,459 for the period 8/1/11 to 7/31/12
These studies will provide new information on the molecular mechanisms by which chondrocyte integrin receptor signals regulate production of enzymes that cause excessive degradation of the cartilage matrix in arthritis to develop novel therapeutic targets.
- A systems biology approach for discovery of novel pathways in osteoarthritis
Awarded $27,947 for the period 8/1/09 to 7/31/10
Source: Arthritis Foundation/WFUHS
- WFU Older Americans Independence Center, Molecular Science Resource Center
Awarded $15,295 for the period 6/1/09 to 7/31/10
- Computational modeling of dendritic cell maturation
Awarded $84,112 for the period 5/1/10 to 4/30/11
Dendritic cells (DC) activate the adaptive immune system to clear infections. First, however, their potency must increase in a tightly regulated process termed maturation that involves gene expression changes, intracellular trafficking, cytoskeletal modifications, and mobilization to lymphoid organs. Very few studies have examined the full time-course of this process, and none have attempted to model it. This project aims to explain DC maturation at a systems level. First, following treatment with a model viral infection, significantly expressed DC genes will be identified and clustered over time to assess the dynamics. Second, the relationships between significantly expressed genes will be studied to identify networks of interactions. Finally, genes involved in subnetworks will be modeled to identify cause-and-effect, rather than merely correlative, relationships. Because DC maturation is so pivotal to protective immunity, a broader understanding of its gene expression program and the comprehensive transcriptional regulatory network underlying it is necessary for the design and development of vaccines and therapies against infectious agents.
- with David J. John, Computer Science, and Edward E.
Algebraic and Statistical Models of Redox Signaling
Awarded $123,379 for the period 4/1/08 to 3/31/09
An interdisciplinary research group spanning the Reynolda and Health Sciences campuses aims to develop theory, algorithms, computational tools, and research methodologies for network modeling of redox-regulated events in human cells. Recent research indicates that redox-regulated networks are central to cellular communication under a variety of normal and diseased conditions, including cancer, neurodegenerative diseases, and aging. This project will (1) identify a comprehensive set of cellular proteins modified at cysteine residues as a result of redox-dependent signaling; (2) correlate the concentration of a given cellular perturbant and its associated redox signal; 3) associate networks with particular perturbants; and 4) produce both topological and dynamic models of the cellular network associated with these pathways. These models will then be compared to other data on protein/protein interactions and kinase cascades to produce a more comprehensive model of cellular regulation and its biological outcomes.
- Integrated Process for Functional Site Feature Analysis
Awarded: $167,800 for the period 8/1/07 to 7/31/08
Sequence and structural genomics projects have identified and predicted
molecular functions in proteins, yet researchers still cannot determine
the biological mechanisms of, for example, catalysis or substrate
specificity or inhibitor binding, without detailed biochemical and
biophysical analysis of each protein. While structural genomics projects
are providing the necessary data, they are not being used to reveal
the general principles underlying biological mechanism.
This project uses sequence, structure, bioinformatics, and biophysical
to characterize the molecular function sites of 6 protein superfamilies,
with the following objectives: 1) characterizing the sequence and
structure of functional site features and using the results to develop
methods for clustering the peroxiredoxin family; 2) analyzing the
electrostatics at peroxiredoxin functional sites and testing them
experimentally; 3) integrating electrostatic, sequence, and structural
information to create a robust profiling method that can identify
peroxiredoxin subfamilies; and 4) using it to create active-site
signatures and profiles for a well-studied and important set of protein
superfamilies. The data will be made widely available.
This detailed functional site analysis of 6 superfamilies will
yield insights into biological mechanisms, leading to hypotheses
be experimentally tested. In the long term, the methods will enable
more accurate functional site identification from sequence. The
development of general concepts for identifying and classifying
site features will advance the design of enzymes with improved,
altered, or novel activity and inhibitors (or lead compounds),
an early step
in the drug-discovery process. Students involved in this project
will gain cross-disciplinary molecular biophysics training that
will fuel successful scientific careers. In addition, the project
a new interdisciplinary molecular biophysics course in which students
are introduced to computational methods and work to interpret data
in terms of protein structure. Graduate and undergraduate students
from biochemistry, biology, chemistry, and physics as well as researchers
from a local biopharmaceutical company studied the peroxiredoxin
family in this course and were introduced to the ideas and communication
skills necessary in an interdisciplinary research project.
- with Elizabeth Hiltbold, Microbiology and Immunology, WFUHS
Networks of Dendritic Cell Maturation Induced by Bacteria
Awarded $20,000 for the period 5/06 to 5/07
Source: WFU Cross-Campus Collaborative Research Fund
Dendritic cells (DCs) are uniquely qualified to activate naive
T cells because of their ability to sense and to capture pathogens,
to degrade them within the cell, and to present their antigens
on the cell surface. In a process known as maturation, DCs are
transformed from poor T cell stimulators to highly potent T cell
activators through a series of morphological and functional changes.
This process is tightly regulated at the transcriptional level,
and while several aspects have been well characterized, the program
that drives it remains unclear, especially in response to intact,
live bacteria, a physiologically relevant stimulus.
Most bacteria express a variety of components that stimulate
several pattern-recognition receptors, and many are able to access
distinct groups of receptors at several intracellular sites,
including the plasma membrane, phagosomes, and even cytoplasm.
The PIs hypothesize that the interactions between multiple pattern-recognition
receptors that are triggered by live Listeria are critical for
maximal activation of antigen-presenting cells.
Microarray technology is a powerful methodology for systemically
studying the time-course of global changes in many biological
systems. The project couples this technology with computational
biology to develop network models of functional classes of genes
expressed when bacterial infection induces DC maturation. Completion
of the two specific aims will provide the preliminary data and
framework models of DC maturation necessary to develop a competitive
- with Jason Grayson, Microbiology & Immunology, WFUHS
Computational Modeling of Reactive Oxygen Intermediate Signaling
in CD8+ T Cells
Awarded $15,000 for the period 5/6/05 to 5/15/06
Source: WFU Cross-Campus Collaborative Research Fund
CD8+ T cells are critical for clearing viruses, tumors, and
certain bacteria. Understanding the molecular mechanisms that
these cells’ proliferation and death is critical
for optimizing HIV and cancer vaccines and developing treatments
Recently, the team demonstrated that treatment with MnTBAP,
an anti-oxidant, reduces both the expansion and contraction
CD8+ T cells in vivo during viral infection. With treatment,
proliferation decreased ten-fold, while the contraction
was almost completely
blocked. This result demonstrates that increased immunological
memory can be generated from a smaller expansion of virus-specific
cells. Despite these intriguing results, the molecular
mechanisms by which reactive oxygen intermediates (ROI)
and death have not been determined.
The team hypothesizes: (1) cellular proliferation pathways are
very sensitive to ROI levels, but activating death pathways
a higher and chronic level of stimulation; and (2) different
levels of ROI induce different redox responses that can be identified
as part of a biological network. These hypotheses will be tested
by (1) identifying cellular proteins oxidized at cysteine residues
by high- throughput proteomics following T cell activation in
vitro; and (2) developing framework models of the proteins involved
in redox signaling networks in antigen-specific CD8+ T cells
and compaing their topologies for different incubation conditions
and different segments of the culture cycle.
- with S. Bruce King, Chemistry
Profiling of Redox-Sensitive Signaling Proteins
Awarded $18,478.36 for the period 5/1/06 to 4/30/07
Reynolds Professor Fetrow will direct the bioinformatics component
of this ambitious project to devise large-scale methods to identify
proteins that respond to cellular redox changes. The team aims
to integrate analytical protein chemistry, cell biology, and bioinformatics
to test the hypothesis that redox signaling affects the initiation
of cell proliferation and transformation. Successful development
of this technology will lead to future broad-scale research with
implications for cancer prevention and treatment.
- Lab-on-Bead-enabled, next-generation sequencing for cancer drug discovery
Awarded $113,111 for the period 11/1/12 to 10/31/13
Source: NIH; NanoMedica LLC
This project combines an encoded macrocycle library screening and candidate molecule selection to discover new anticancer drug candidates. This next generation Lab-on-Bead sequencing and selection method is designed to discover more with less: it requires only tiny amounts of target molecules and library candidates and may ultimately be able to screen up to 108 drug candidates in less than a day.
- Accelerating Drug Discovery: Front-end Library Screening for Biological Relevance
Awarded $250,000 for the period 1/1/11 to 12/31/12
The development of vast, nucleotide-encoded chemical libraries holds extraordinary promise for discovering new drug candidates, diagnostic reagents, and chemical probes, but their exploitation requires an effective selection process. This collaboration among Cancer Biology, Chemistry, and Physics teams and an NC-based commercial partner, NanoMedica, Inc., couples novel, highly efficient capillary electrophoresis and whole-cell preselection methods to create nanobeads functionalized with multiple copies of a unique, nucleic-acid-encoded chemical, followed by the identification and extraction of target-bound beads using inverted and atomic force microscopes or a micropipette system. Nanoselected candidates will be identified by PCR amplification of their coding sequences followed by validation assays.
- Mechanical Properties of Native and Variant Fibrin Fibers
Awarded $20,000 for the period 7/1/09 to 6/30/10
Source: American Heart Association
This project studies the mechanical properties of individual fibrin fibers and fibrin fiber junctions in a fibrin clot. The strength and failure mechanisms of branching points will be compared to those of individual fibers. The goal is to construct a realistic mechanical model of a blood clot. Atomic force microscopy will be used to record force data while stretching a fiber, and an inverted fluorescence microscope allows the manipulation to be viewed and recorded. The stress/strain curves produced can be used to determine the visco-elastic modulus, elastic modulus, force relaxation rates, modulus stiffening at high strains, and energy loss.
- Determining the Mechanical Properties of Single Fibrin Fibers
Awarded $225,000 for the period 7/01/07 to 6/30/10
Blood clots perform the essentially mechanical task of stemming blood flow. However, the mechanical properties of clot constituents are largely unknown. Besides platelets, which initially aggregate at the site of a wound, the major structural component is a branched network of fibrin fibers. A novel technique, combining atomic force and fluorescence microscopy in a single instrument, will be used to systematically study the mechanical properties of single fibrin fibers and a variety of mutants under a variety of conditions.
- Visco-elastic properties of fibrin fibers
Awarded $10,000, Spring 2007
Source: WFU Science Research Fund
The mechanical properties of blood clot constituents are largely
unknown, which has seriously hampered our full understanding of
clotting and development of good models. Their major structural
is a network of fibrin fibers that critically depends on the fibers’ mechanical
properties and the properties of the junctions between fibers.
Little is known about these nanoscopic features because a good
to study them has been lacking. This project aims to develop a
novel technique, combining atomic force and fluorescence microscopy,
study the mechanical properties of single fibrin fibers. The tip
of the atomic force microscope (AFM) will be used to laterally
stretch fluorescently labeled fibrin fibers that are suspended
in a striated substrate, while the fluorescence microscope images
this process. This experimental design yields a well-defined, easy-to-analyze
geometry ideal for measuring stress-strain curves of fibrin fibers.
The 16 viscoelastic characteristics of fibrin fibers that define
their mechanical behavior will be quantified for several parameters,
such as temperature and fiber radius. Fibrinogen variants will
provide insights into their molecular mechanisms and the fibrin-fibrin
that affect them. This pioneering technique should apply to many
biological and nonbiological fibers and provide an entirely new
understanding of blood clots, heart attacks, strokes, and related
project will include two graduate and three undergraduate students.
- Kinesin Force-Velocity in Curves when 1, 2, or 3 Motors Transport
a Single Load
Awarded $5,013 for the period 8/1/07 to 7/31/08
The project’s long-term objective is to elucidate, at the
molecular level, how the motor protein kinesin transports vesicles
from a neuron’s cell body to its axon tip, a distance of
as much as 1 meter, in only 4 days. The velocity/force relation
kinesin motor is well understood when the motor is in solution,
and the viscous work load on it is small. However, within a cell,
viscolelastic drag force opposing the motor is at least 100 times
greater, so 2-5 motors are probably required to pull a single vesicle.
Quantitative velocity/force curves have been obtained for 1 kinesin
but not for the 2, 3, or more active motors actually needed to
pull a single load in vivo, and qualitative data on the effect
motors are contradictory.
The project will test the hypothesis that 2 or more motors pulling
a single cargo will share the load equally. It aims to measure velocity/force
curves for 1, 2, and 3 kinesins over a physiologically realistic
force range. Using speckled microtubules to provide numerous fiduciary
marks along the length of each microtubule will greatly improve the
spatial precision of tracking over classical gliding assays, which
use uniformly labeled microtubules, and the temporal precision will
be 0.1s or better. If the gliding microtubule can be tracked for
5-10s, the pattern of velocity changes will reveal the number of
active motors. Force will be generated by viscous drag and magnetic
beads bound to the gliding microtubule.
The exceptional length of some neurons places exceptionally stringent
demands on their vesicle transport systems and suggests that some
neuronal disease may originate in a transport system failure. Mutations
in microtubule motor proteins have been shown to cause disease phenotypes
in Drosophila and degenerative diseases of the human nervous system.
A more quantitative analysis of multiple motor mechanics will expedite
the identification of degenerative diseases associated with defective
transport and facilitate rational intervention.
- Kinesin Force-Velocity Curves when 1, 2, or 3 motors transport a
Awarded $20,000 for the period 1/27/06 to 1/26/07
Source: Dreyfus Foundation
Dr. Holzwarth is one of 14 national winners of the prestigious Senior
Scientist Mentor Award for 2006. Faculty with emeritus status who
maintain active research programs in the chemical sciences are awarded
grants of $10,000 annually for two years to support undergraduate
research under their guidance.
The maximum force generated by 1 kinesin motor protein molecule
in vitro is 7 pN. There is indirect evidence that in cells, several
kinesin motors must cooperate to move a single vesicle, because the
drag force that must be overcome is 5 pN. We will measure velocity-force
curves for 2, 3, or 4 kinesin motors pulling a single load in vitro
against a carefully measured viscous or magnetic force.
N. A. W. Holzwarth
- with Timo Thonhauser, Physics, and Akbar Salam, Chemistry
ES12: 24th Annual Workshop on Recent Developments in Electronic Structure Theory
Awarded $10,000 for the period 6/1/12 to 5/31/13
Source: US Department of Energy (DOE)
The workshop brings investigators in electronic structure theory from around the world to the WFU campus. Invited presentations and contributed posters describe new methods for computing previously inaccessible properties of materials, breakthroughs in computational efficiency and accuracy, and novel applications of these methods to the study of molecules, liquids, and solids. It represents a valuable opportunity for students, postdocs, and senior researchers to present their ideas and learn from each other. Funding contributes to its success especially by keeping participant costs low and making attendance more widely accessible.
- ES12: 24th annual workshop on recent development in electronic structure theory
Awarded $5,000 for the period 5/15/12 to 5/14/13
Source: Army Research Office (ARO)
Wake Forest University will host the workshop from 5-8 June 2012 (http://es12.wfu.edu). Organized with Timo Thonhauser, Physics, and Akbar Salam, Chemistry, it will bring together electronic structure theorists from universities, colleges, institutes, and laboratories around the world. Invited presentations and contributed posters will describe new methods for computing previously inaccessible properties of materials; breakthroughs in computational efficiency and accuracy; and novel applications to study molecules, liquids, and solids. Funding will keep participant costs low and make attendance more accessible.
- First Principles Simulations of Battery Materials
Awarded $200,000 for the period 9/1/11 to 8/31/13
Advances in battery capacity, safety, and stability are needed to meet projected energy storage needs. First principles simulations of their materials will provide a detailed, atomic-level understanding of their conduction mechanisms to explore optimal stoichiometries and structures. Simulations using simple atomic level models will also explore the relationship of the electrolytes’ microscopic and macroscopic properties. Another project is designed to increase the physical accuracy of the simulation techniques for materials containing the localized orbitals typically found in cathode materials. Training students to perform computational materials research is a large part of this effort. With the help of colleagues at Winston-Salem State University, it hoped that minority students will be among those attracted to this effort.
- Computational Study of Transition Metal Phosphate Materials
Awarded $143,000 for the period 6/30/04 to 6/29/07
This project will perform a systematic computational study
of several crystalline transition metal phosphate materials
exhibiting a wide range of interesting physical and chemical
properties that are not completely understood. Several are naturally
occurring minerals of geological interest; many have various
polymorphic geometric and magnetic structures; and some, whose
electrochemical properties show technological promise in the
battery industry and catalysis applications, have recently generated
a wealth of experimental results.
The proposed computer simulations will develop our qualitative
and quantitative understanding of these materials' structural and
magnetic transformations and properties of technological interest.
Because of the special properties of transition metals in narrow
band gap materials, some aspects of the proposed calculations will
challenge the current state-of-the-art in computational formalism
and coding. In particular, their electron/electron interactions
are critical for determining the materials' properties but difficult
to evaluate accurately. A tangential project will develop a new
approach for examining many electron systems based on the knowledge
of their electron pair states.
- Computational Tools for Detailed Simulations of Materials
Awarded $336,000 for the period 7/1/04 to 6/30/09
This project aims to develop computational tools for accurate and
efficient modeling of the bulk and surface properties of materials
for fundamental studies and technological design. The main goals
(1) To investigate and to incorporate several new state-of-the-art
optimization and iteration acceleration methods into the materials
modeling codes, such as the use of surrogate functions and dynamic
(2) To develop algorithms and codes for the efficient solution of
boundary value problems arising in the study of surfaces and interfaces
of materials, incorporating input from bulk simulations;
(3) To share the codes and results with the research community,
providing a forum for comparing the accuracy and efficiency of the
leading computational methods.
Preliminary results on the use of surrogate functions for structural
optimization and the development of surface algorithms are very
encouraging. Based on the so-called projector augmented wave (PAW)
method of Bloechl, a code for density functional calculations of
periodic solids is shared with the electronic structure community
from the website http://pwpaw.wfu.edu and through various collaborations.
The PAW method combines the best features of pseudopotential and
- Spintronics for novel device application and metrology advancement
Awarded $117,140 for the period 10/1/12 to 9/30/13
Source: National Institute of Standards and Technology
With recent advances in technology, the demand for faster data processing and greater memory capacity is urgent in the electronics industry. Current metal oxide semi-conductor field effect transistors (MOSTFETs) are rapidly reaching their physical limit. This project exploits an alternative approach to achieve drastic improvements. Spin electronics, or spintronics, can provide greater performance with lower power consumption and integrate with current electronics technology. This project will develop novel devices by discovering materials that enable a long spin transport; developing methods for efficient spin generation and detection; and integrating spintronic functionality in current electronic systems.
- NSF-NIST collaborative research on electrical and optical properties of novel binary donor-acceptor compounds
Awarded $75,126 for the period 8/1/12 to 7/21/14
Source: NSF/UNC-Chapel Hill
The seemingly-infinite variety of organic compounds presents the prospect of tailoring materials with any desired properties—truly “materials by design.” To date, monomolecular organic semiconductors, such as oligoacenes, oligothiophenes, and their derivatives, have shown the best performance, but it is becoming clear that their range of properties is rather restricted. The transition to binary- and multicomponent materials promises discovery of unexpected properties. Charge-transfer (CT) compounds (salts) composed of two different organic molecules, one acting as donor (D) and the other as acceptor (A), are an example of an organic binary system. The intermolecular interactions between D and A, especially electron transfer, allow novel functionalities. This project grows single crystals of binary compounds formed from organic or inorganic donors or acceptors and explores their physical properties to identify the most promising candidates for electronic devices, light-emitting diodes, and solar cells.
- Summer Undergraduate Research Fellowship (SURF)
Awarded $8,531 for the period 5/1/12 to 9/30/12
Source: National Institute of Standards and Technology (NIST)
With recent advances in technology, electronics industry demand for faster data processing and higher memory capacity is urgent. The metal oxide semiconductor field-effect transistors (MOSFETs) currently in use are rapidly reaching their physical limit, and implementing faster, higher capacity requires very high energy use, which is detrimental to the environment and not economically feasible. This project focuses on an alternative approach – spin electronics, or spintronics, which is not volatile and consumes very little power. A Wake Forest Physics major, Alyssa Brigeman (2013), will spend 10 weeks this summer, working “elbow-to-elbow” with some of the world’s leaders in spintronics from the NIST NanoElectronic Device Metrology Group of the Physical Measurement Laboratory.
- High-conductivity in Binary Organic Single Crystals for Electronic Applications
Awarded $54,696 for the period 8/1/11 to 7/31/12
The study of new binary organic compounds could open a large range of functionalities not manifest in monomolecular solids and create new electronics and optoelectronics applications. The graduate students who participate in this project will gain broad experience in a range of physical characterization techniques, device fabrication and characterization, quantum-chemical computational methods, and crystal growth. Undergraduates will be exposed to exciting interdisciplinary topics and a stimulating collaborative training environment. Results will be integrated into courses taught by the co-PIs at the undergraduate and graduate levels, including special-topics courses in organic electronic materials and devices. They will also be used in public outreach activities sponsored by local science museums.
- Patterning Organic Thin-Film Transistors by Differential Microstructure
Awarded $330,000 for period 6/1/11 to 5/31/14
The ability to pattern organic thin films is crucial to manufacturing organic electronic devices with better performance and reduced power consumption. Progress has been impeded by many conceptual and practical problems related to their degradation when exposed to conventional lithography processes. This project will develop reliable, reproducible methods to simultaneously deposit and pattern organic field-effect transistors at low-cost and moderate temperatures. The presence/absence and type of self-assembled monolayers (SAMs) will promote different orientations in the organic semiconductor molecules forming the thin film. A high degree of order will enhance conductivity, while mixed orientations will lead to low conductivity regions where organic semiconductors can be selectively deposited on pretreated surfaces to achieve self-patterning at low cost. Results will elucidate physical processes that originate at organic/dielectric and metal/organic interfaces and lead to development of low-cost, high-yield methods for fabrication of high-performance organic electronic devices.
- Low-cost Organic Electronics: Let Molecules Do the Work
Awarded $5,000 for the period 6/1/10 to 5/31/11
Source: Oak Ridge Associated Universities
Despite remarkable achievements in the field of organic (plastic) electronics, many problems remain. Patterning is a critical step in fabricating organic thin-film transistors (OTFTs); it reduces power consumption and increases performance by minimizing parasitic current paths. However, photolithography techniques developed for inorganic semi-conductors damage weak organic semi-conducting materials and degrade device performance. Unfortunately, methods to solve this problem limit resolution and fail when scaled to large-area processing. This project will exploit unique film-forming properties to develop novel, low-cost, large-area patterning techniques for organic electronic devices. Patterning will be efficiently induced by manipulating the chemical and physical interactions so that differential microstructure forms at the contacts, dielectric materials, or self-assembled monolayers (SAMs) on their surface. The program offers exciting collaborative and interdisciplinary research opportunities and a stimulating environment for student training.
- Nondestructive deposition of electrical contacts on organic semi-conductors
Awarded $126,741 for the period 6/30/11 to 9/30/12
Despite recent improvements in the performance of organic electronic devices, efficient contact deposition remains a major obstacle to reliability. Conventional methods damage the weak organic materials below the metal electrodes. This project will use nano-transfer printing (NTP), which preserves organic semi-conductor quality at the interface with metals, while its low thermal budget enables fabrication of large-area, light-weight, low-cost, flexible electronics on plastic substrates. NIST researchers have successfully used it to fabricate electronic devices; this project will fabricate high-performance organic field-effect transistors. A second goal is to fabricate devices with competitive performance and use them to gain correct information on charge injection and transport and charge trapping and detrapping in organic semi-conductors.
Daniel B. Kim-Shapiro
- Role of nitrite reduction to NO by hemoglobin in control of fetal vascular tone
Awarded $32,880 for the period 6/1/11 to 5/31/12
Source: NIH/Loma Linda University Adventist Health and Science Center
Hypoxic/ischemic insult (HI) is a common cause of perinatal morbidity and mortality. Nitric oxide (NO) is an endogenous defense against it, dilating blood vessels to increase oxygen delivery and decreasing oxygen consumption at the mitochondrial level. Although hemoglobin rapidly scavenges free NO, limiting its half-life in blood to milliseconds, de-oxyhemoglobin can reduce nitrite to NO, which provides significant protection during HI in adults. The higher concentrations of nitrite, hemoglobin, and H+ in fetal blood favor the reaction; when hemoglobin is 40-60 percent oxygenated, compared to 0 or 100 percent, nitrite reduction is up to 60-fold greater, again suggesting high NO production from nitrite and de-oxyhemoglobin in the fetus. These studies will provide the first thorough assessment of this hypothesis and show how nitrite might be used to treat perinatal HI. Dr. Kim-Shapiro directs EPR measurements performed mainly by a graduate student and contributes to the design and analysis of experiments performed at both universities.
- Storage lesions in banked blood due to disruption in nitric oxide homeostasis
Awarded $137,496 for the period 8/1/12 to 7/31/13
Source: NIH/University of Pittsburgh
Storing red blood cells can impair their functionality and integrity, contributing to poor transfusion results. This project tests the hypothesis that storage lesion is largely due to dysregulation of nitric oxide (NO) homeostasis. Cell-free hemoglobin and microparticles released during hemolysis increase NO scavenging and decrease NO production. An array of clinical, molecular biology, biophysical, and biochemical tools will be applied to characterize the NO storage lesion in vitro and in chimeric mouse models, a canine model, and human studies. Therapeutics to restore NO homeostasis will be explored in these systems.
- Exercise, Weight Loss, and Arterial Stiffness in Obese Older Adults
Awarded $16,174 for the period 7/1/12 to 6/30/13
Source: American Heart Association/WFBH
Several studies associate obesity with arterial stiffness in the elderly, possibly due, in part, to reduced nitric oxide (NO) bioactivity and increased oxidative stress. Weight loss and aerobic exercise training are generally effective in improving arterial stiffness in middle-aged adults, but in older individuals, who are largely overweight or obese, exercise alone is ineffective, possibly due to the vasculature’s impaired ability to increase NO with exercise. This project will determine whether combining an exercise intervention with diet-induced weight loss improves arterial stiffness more than exercise alone in older, obese adults enrolled in a 5-month randomized controlled trial.
- with S. Bruce King, Chemistry
Effects of Nitric Oxide in Sickle Cell Blood
Awarded $ 392,420 for the period 5/1/12 to 4/30/13
The project will elucidate the biochemistry and biophysics of nitric oxide (NO) in sickle cell blood and its use as a treatment for the disease. NO may benefit patients as a vasodilator, decreasing red blood cell sickling and sickle cell adherence and improving oxygen transport. However, NO biology in both sickle cell and normal blood is not well understood, and previous studies report contradictory results. Results from sickle blood will be compared to those in 1) normal blood; 2) preparations of isolated normal and sickle red blood cells; and 3) purified hemoglobins. A variety of spectroscopic and other biophysical tools, some developed specifically for this project, include microscopy, ektacytometry, ultracentrifugation, stopped and quench-flow mixing, laser photolysis and diffraction, chemoluminescence, electron spin resonance, nuclear magnetic resonance, and absorption spectroscopy.
- Enzymatic activity of myoglobin as a nitrate reductase that regulates hypoxic NO
Awarded $27,413 for the period 4/1/12 to 3/31/13
Source: NIH/University of Pittsburgh
Dr. Kim-Shapiro and his team will perform kinetic analysis on myoglobin mutant proteins using electron paramagnetic resonance (EPR) and model reactions of myoglobin and nitrite in the cardiomyocyte.
- Noncompetitive Supplemental Application for R37 HL58091
Awarded $10,000 for the period 3/1/10 to 4/30/10
In sickle cell disease, a mutant form of hemoglobin polymerizes when exposed to low oxygen tension. The red blood cells become rigid, blocking vessels and causing significant morbidity and mortality. Sickle red blood cells are also fragile, rupturing in the circulation. For many years, this problem was not viewed as crucial, but several groups have recently proposed that efficiently released cell-free hemoglobin scavenges NO, leading to an NO-related deficiency associated with sickle cell disease. Nitric oxide (NO) is currently being tested as a treatment; synthesized in blood vessel endothelial cells, it diffuses to neighboring smooth muscle cells, where it signals muscle relaxation and vasodilation.
This project aims to elucidate how hemoglobin mutation increases red blood cell fragility and why NO scavenging is reduced in red cell-encapsulated, as opposed to cell-free, hemoglobin. Differences in how NO reacts in sickle cell and other blood will be determined, and a mechanism using the anion nitrite to restore effective NO response explored. The participating laboratories have recently shown that, contrary to the existing paradigm, nitrite acts as a vasodilator in human circulation, possibly due to a novel, allosterically controlled function of hemoglobin. The study employs an array of biophysical techniques and has developed techniques to study whole blood to assess physiologically relevant conditions.
- A Multifunctional Blood Substitute (MBS) for Field Resuscitation of Polytrauma Combat Casualties with Brain Injury and Concomitant Hemorrhagic Shock
Awarded $15,000 for the period 9/15/09 to 9/14/10
Source: Army Research Office (ARO)/University of Pittsburgh
Currently, no blood substitute is FDA approved, a major problem on the battlefield. Past and current attempts scavenge endogenous nitric oxide, which is critical to vascular tone and hemostasis, among other things. This project will build on the team’s recent discovery that hemoglobin produces nitric oxide from nitrite to optimize this function in a blood substitute. In particular, combinations of oxidized and nonoxidized hemoglobin products and nitrite will be explored for their ability to produce nitric oxide activity. The Wake Forest team will use electron paramagnetic resonance (EPR) spectroscopy to analyze blood or plasma samples containing the blood substitute to determine whether Hb submicromolar amounts of these hemoglobin species can be measured in the background of millimolar quantities of (EPR silent) deoxygenated and oxygenated hemoglobin.
- with Bruce King, Chemistry; Gary Miller and Jack Rejeski, Health and Exercise Science; and Janine Jennings, Psychology
Effects of Nitrite Diet on Functional Health in Older Adults: A Preliminary Study
Awarded $9,375 for the period 1/1/09 to 12/31/09
Source: WFU Science Research Fund
Until recently, nitrite was thought to be biologically inert. However, due, in part, to work in the Kim-Shapiro and King labs, it is now recognized as an important signaling molecule because it can be converted to the established signaling molecule nitric oxide (NO). Emerging evidence suggests that loss in NO bioavailability contributes to conditions associated with impaired health during aging. The long-term goal of this project is to examine the extent to which nitrite (dietary or otherwise) can improve functional health in older adults. It will test the hypothesis that nitrite can compensate for the loss in NO bioavailability with aging. Phase I will develop a diet that increases nitrite in the plasma. Phase II will explore the extent to which this diet affects older adults’ cognitive performance. Results will elucidate nitrite/NO biology and physiology and potentially improve the lives of untold numbers.
EPR Work for Cardioxyl,
Awarded $3,564 for the period 2/22/08-2/21/09
Source: Cardioxyl Pharmaceuticals, Inc.
Cardioxyl Pharmaceuticals aims to develop new therapeutic agents for treating cardiovascular diseases. In this project, Wake Forest will assess whether electron paramagnetic resonance spectroscopy can be used to measure the dosing of a particular therapeutic agent.
- with Bruce King, Chemistry
Nitric Oxide Donor Compounds for the Treatment of Hemolytic Conditions
Awarded $162,657 for the period 1/1/09 to 12/31/09
Nitric Oxide (NO) is synthesized in the endothelial cells surrounding blood vessels and signals smooth muscles to relax and increase blood flow. Hemoglobin (Hb) actively scavenges NO. In normal physiology, its scavenging is reduced due to its compartmentalization in red blood cells, but in several diseased conditions, including hemolytic anemias, such as sickle cell disease and paroxysmal nocturnal hemoglobinuria (PNH), thalassemia intermedia, malaria, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and cardiopulmonary bypass, Hb is released into the plasma compartment and can efficiently scavenge NO. This increased NO scavenging leads to a host of complications contributing to morbidity and mortality.
Administering NO through inhalation restores normal NO responsiveness and shows promise as a treatment, but it is not practical for chronic treatment. This project tests and, to some extent, synthesizes compounds that may eventually be taken intravenously or orally. Unlike many therapeutic compounds, they will be cell-impermeable, acting in the plasma compartment to react preferentially with cell-free Hb and inactivate its NO scavenging ability.
- with Janice D. Wagner, Comparative Medicine
Effects of Short-Term Hyperglycemia on Arterial and Liver Redox-Active
Awarded $15,672; $6,900 Reynolda campus,
$8,772 Health Sciences
Source: WFU Cross-Campus Collaborative Research Fund
Cardiovascular disease (CVD) is the primary cause
of morbidity and mortality in both Type 1 and Type 2 diabetics,
mortality rates are 2-8-fold higher in diabetics
than nondiabetics. Only part of the problem can be explained by
typical risk factors,
such as plasma lipids and blood pressure. This project
aims to explain how hyperglycemia influences production of oxygen
free radicals in diabetic arteries and how it might
to atherosclerosis. Transition metal ions, such as
iron or copper, are excellent catalysts for producing free radicals,
and iron disturbances have been seen in diabetics.
results in diabetic monkeys show increases in transition
metal-catalyzed aortic protein oxidation in parallel with an increase
after six months. Using diabetic cynomolgus monkeys,
the project will investigate how short-term hyperglycemia affects
of redox-active iron species in arteries, to determine
their involvement in atherosclerotic processes, and liver, which
plays a central role in iron metabolism. Redox-active
species will be measured in intact artery and liver
tissues, snap-frozen in liquid nitrogen, and kept at -80°C,
using electron paramagnetic resonance spectroscopy. Immunoblot
will measure relative amounts of proteins involved
in iron storage (ferritin), iron transport, hemoglobin, and heme
- Effects of Nitrite in Sickle Cell Blood
Awarded $343,920 for the period 12/1/06 to 11/30/07
Sickle cell disease is caused by a mutant form
of hemoglobin that polymerizes when exposed to low oxygen
makes the red blood cells rigid so that they block
some blood vessels, leading to significant morbidity and mortality.
is currently being tested as a treatment for sickle
cell disease due to its role as a vasodilator among other things.
synthesized in blood vessel endothelial cells and diffuses
to neighboring smooth
muscle cells, where it acts as a signaling molecule,
causing muscle relaxation and vasodilation. Sickle red blood cells
rupturing during transit. For many years, this hemolytic
anemia was not viewed as critical to the disease’sl pathophysiology.
However, several groups have now begun to re-examine
the consequences of hemolysis and the hypothesis that released
efficiently scavenges NO, causing a deficiency.
This project aims to elucidate 4 mechanisms: 1) How does the hemoglobin
mutation lead to increased red blood cell fragility? (2) How does
the reduced NO scavenging by red cell-encapsulated hemoglobin compare
to cell-free hemoglobin? (3) How does NO react in sickle cell blood
compared to normal blood? (4) How can an effective NO response
be restored in patients using the anion nitrite? The laboratories
participating in this project have recently shown that, contrary
to the existing paradigm, nitrite acts as a vasodilator in human
circulation, possibly due to an allosterically controlled function
The study employs an array of biophysical techniques,
including electron paramagnetic resonance spectroscopy, kinetic
spectroscopy, laser diffraction, and computational simulations.
Techniques have been developed so that these studies can be made
on whole blood, to assess physiologically relevant conditions.
- Nitrite and Nitric Oxide in Sickle Cell Blood
Awarded $103,680 for the period 12/1/08 to 11/30/09
Source: NIH, Independent Scientist
Career Development Award
This career award will reduce Dr. Kim-Shapiro’s teaching
and service load so that he can spend greater than 75% of his
time on research, which focuses on the effects of nitric oxide
(NO) in sickle cell blood. Patients with sickle cell anemia
have been shown to have abnormal NO-related vasoactivity due to
cell-free hemoglobin scavenging NO. NO therapy may restore normal
Recently published data also suggest that NO may upregulate fetal
hemoglobin and thereby reduce sickling.
Dr. Kim-Shapiro is also a key collaborator on
a study of the NO-donating properties of hydroxyurea, an FDA-approved
drug for sickle cell disease. He has participated in some recent
studies suggesting that nitrite is converted to NO by deoxygenated
hemoglobin and thus serves as a reservoir for NO in the body and
will expand his studies to investigate the effects of nitrite
in sickle cell blood. Finally, he plans to develop noninvasive
imaging tools to study pathology of the microcirculation in patients
with sickle cell disease and the effects of therapeutics.
- Cellcraft: Exploring the Cell through Computer Games
Awarded $25,490 for the period 6/1/09 to 5/31/10
Source: MacArthur Foundation
The Cellcraft project is a video game in which players explore the inner workings of a cell while gaining skill in organizing, planning, coordinating, delegating, and logic. Students Anthony Pecorella and Yuri Shtridelman are the co-principal investigators.
- Better, Faster Live-Cell Imaging: Motion-Enhanced DIC (MEDIC) with Fluorescence
Awarded $31,262 for the period 6/16/09 to 10/31/09
All human cells contain machinery for moving submicroscopic cargo. Understanding how is crucial to improving therapies for Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) as well as the overall health of the cell. This administrative supplement creates summer jobs for K-12 teachers and undergraduate students to accelerate development of a novel light microscopy imaging system, ideal for visualizing cargo transport in living cells. In summer 2009, senior personnel and an undergraduate intern will improve the software that facilitates simultaneous fluorescence-MEDIC imaging and port it to standard PC graphics cards for wider use. Two undergraduates, one middle-, and one high-school teacher will culture neurons and smooth muscle cells in the PD/PI’s new tissue culture facility, acquiring the initial imaging data and returning in summer 2010 to perform follow-on experiments. Their effort will greatly accelerate the parent project, and they will gain cutting-edge skills that will motivate their own and their students’ careers in the biomedical sciences.
- NanoSelection of Customizable Biotechnology Reagents
Awarded $20,000 for the period 12/08 to 11/30/10
Source: NanoMedica, Inc.
Biotechnology demands cost-effective, customizable reagents for such applications as detection, screening, purification, and labeling. Aptamers – single-stranded nucleic acid molecules with properties comparable to monoclonal antibodies – have clear advantages over antibody-based diagnostics. Large quantities can be created easily with high purity and reproducibility using solid-state synthesis techniques. However, screening them for specific target-binding is difficult; existing selection strategies are tedious; and commercialization is often stifled by aggressive patent enforcement. Consequently, their versatility and commercial impact have largely gone untapped.
The proposed technology offers a novel, integrated platform to accelerate the discovery of commercially useful aptamers. It avoids time and reagent costs and patent barriers by directly selecting tight-binding aptamers without using proprietary amplification cycles; eliminates the “black box” of previous screening schemes by visualizing every tight-binding event individually; and allows users to customize the strength of aptamer-target affinity.
- Drug Discovery at the Nanoscopic Level: Lab-On-Bead™ Processing of Encoded Chemical Libraries
Awarded $75,000 for the period 7/1/09 to 12/31/09
Finding chemicals that bind molecular targets—even with high-throughput screening—is slow, and most candidates fail physicochemical and biological requirements. Ultrahigh-throughput screening via encoded chemical libraries could improve results with a method to quickly and sensitively screen and identify the encoded chemicals. Lab-on-Bead amplifies and reads out a nucleic acid code at the level of single nanoscopic beads. This project aims to validate Lab-on Bead in partnership with biotechnologists at Harvard University and the Université Louis Pasteur for the eventual production, with the help of NanoMedica, Inc., of bead reagent kits and microfluid instruments to discover new drugs and diagnostics.
- Generating DNA LOBOS: libraries of one-bead, one sequence using an
anchored polymerase chain reaction
Awarded $10,000, Fall 2006
Source: WFU Science Research Fund
This project will create libraries in which each “book” is
a microscopic bead decorated with hundreds of copies of a unique
DNA sequence. These DNA libraries of one-bead, one sequence (LOBOS)
will enable a drug-screening method developed by Associate Professor
Martin Guthold that uses folded DNA strands called aptamers. In this
method, randomized DNA aptamers bind to a drug target, and the one
that binds the tightest is amplified for future use. Hundreds of
identical aptamers must be grouped together, so they can better bind
the target and be properly amplified by PCR (the polymerase chain
reaction). DNA LOBOS will satisfy these important requirements.
- Targeting the MSH2-dependent apoptotic pathway
Awarded $148,233 for the period 3/1/13 to 2/28/14
This project is developing lead compounds for a novel chemotherapeutic that selectively activates a cell-death pathway by binding to specific protein conformations. In addition to its medical relevance, it highlights the importance of dynamics and physics-based modeling, chemical synthesis, cell biology, and animal models in drug design
- Computational biosciences from the Cancer Center support grant
Awarded $10,273 for the period 2/1/12 to 1/31/13
- with Roy Hantgan, Biochemistry
Drug, Design, Discovery and Development – Molecules to Medicines
Awarded $11,939 for the period 6/1/09 to 5/31/10
Wake Forest University will prepare 20 students per year over 3 years to lead North Carolina’s pharmaceutical and biotechnology industries in a novel curriculum that integrates classroom and laboratory learning with work and teaching experience. In the new, multidisciplinary course, Drug Discovery, Design, and Development – Molecules to Medicines, with its companion Drug Discovery VirtuaLaboratory, graduate students and advanced undergraduates in chemistry, biochemistry, and biophysics examine the scientific, medical, economic, entrepreneurial, and ethical aspects of drug development and gain hands-on experience with drug-design software. The most promising compete for 3-month internships, designed by industry partners and mentored by core faculty. These students will then gain teaching skills by sharing their knowledge and experiences in seminars; leading discussions of faculty-assigned problems; and guiding new students with the drug-discovery software.
- with Ulrich Bierbach and Bruce King, Chemistry, and Roy
Molecules to Medicines: Crafting a New Interdisciplinary Curriculum in Drug Discovery
Awarded $7,500 for the period 3/18/08 to 3/19/09
Source: Camille and Henry Dreyfus Foundation
Sparked by keen student interest, Wake Forest’s mandate for entrepreneurship, and the pharmaceutical industry’s need for cross-disciplinary scientists with critical-thinking and teamwork skills, the project prepares students in the biological, chemical, and physical sciences to pursue wider career paths. In a new course, Dreyfus funds will allow promising students, Dreyfus Discoverers, to complete internships in the pharmaceutical and biotechnology industries. They will return to serve as teaching assistants, sharing their knowledge and experiences through seminars and weekly problem sessions.
- Novel theoretical and experimental approaches for understanding and optimizing hydrogen-sorbent interactions in metal organic framework materials
Awarded $94,990 for the period 8/15/2012 to 8/14/2013
Source: US Department of Energy (DOE)/University of Texas-Dallas
This project, part of a large effort that brings together a theorist from WFU and experimentalists from UT Dallas and Rutgers, investigates metal organic framework (MOF) materials for hydrogen storage and gas separation. Research focuses on first-principles electronic-structure simulations to model these materials and investigate their basic physical properties.
- CAREER: Improving electronic structure theory
Awarded $166,825 for the period 9/1/12 to 8/31/17
The research plan builds on the PI’s expertise in ab initio modeling of van der Waals interactions to address the hydrogen storage problem, a critical barrier to a hydrogen economy and an urgently needed alternative fuel. Magnesium borohydride, ammonia borane, and methane-based materials show great potential but release or store hydrogen only at impractically high or low temperatures. While they differ, they are all influenced by van der Waals interactions. The PI proposes: 1) to lower the hydrogen desorption temperature in MGBH42 by destabilization through doping; 2) to lower the desorption temperature in NH3BH3 by substitutions in the hydridic group that will lower the activation barrier; and 3) to determine whether alkanes longer than the methane in H24CH4 can be stable at higher temperatures.
The education plan addresses the economic and educational challenges and inadequate mentoring in academic science in a highly diverse region. The objectives are: 1) to work with the local science museum and schools to create an Energy Zone, including a display, demonstation, teaching module, and informal talks for the general public about alternative energy and hydrogen as fuel; and 2) to develop an interdepartmental mentoring program for graduate students and postdocs to improve their research skills and transition to independent careers.
- Ab-initio materials modeling including van der Waals forces
Awarded $5,000 for the period 6/1/09 to 5/31/10
Source: Oak Ridge Associated Universities (ORAU)
The prestigious and highly competitive Ralph E. Powe Junior Faculty Enhancement Award aims to enrich the research and professional growth of young faculty in a wide variety of fields from over 120 member universities across the USA. This project develops a promising new approach to conducting quantum-mechanical simulations of water, one of the most important substances on earth and crucial to life.
- Toward Large-scale NMR Calculations on van der Waals Systems from First-principles
Awarded $10,000 for the period 1/1/09 to 12/31/09
Source: WFU Science Research Fund
This project relies on new approaches for first-principles calculation of NMR shifts and description of van der Waals forces within density functional theory. Here, they will be stabilized, optimized, and applied to new materials. The long-term goal is to use them to study bio-, nano-, and energy-related materials.
Richard T. Williams
- Physics of scintillator nonproportionality
Awarded $75,000 for the period 2/08/12 to 9/30/12
Source: National Nuclear Security Administration/Lawrence Berkeley National Laboratory
Wake Forest will perform laser measurements on scintillators to develop predictive models.
- Quantifying recombination dynamics in Srl2:Eu2+ with material variations: Mechanisms and scintillator optimization
Awarded $150,000 for the period 7/7/11 to 7/6/14
Source: National Nuclear Security Administration/Fisk University
High-performance scintillators for y-spectroscopy in nuclear nonproliferation applications and homeland security require excellent energy resolution to distinguish neighboring element and isotope lines with minimal time and exposure. For broad implementation, the material should also be inexpensive. The main objectives are (1) to optimize the intrinsic proportionality of light yield from SrI₂:Eu²⁺ and its variations; (2) to lower the cost of optimally performing SrI₂:Eu²⁺; and (3) to experimentally measure parameters to improve SrI₂:Eu²⁺ and to enable numerical modeling to guide discovery of new scintillators.
- fs laser studies of scintillation processes and materials–high-excitation density, transient absorption probes, and role of carrier diffusion
Awarded $13,000 for the period 10/1/10 to 9/30/11
Source: DoE/Regents of the University of California
Experimental investigations seek to improve scintillator resolution by clarifying and then minimizing no-proportional response. They will measure: quenching and decay kinetics of excitations at densities up to 10^22 cm^-3 using fs laser harmonics; picosecond absorption of the important activator charge states and energy-transporting species, such as NAI:T1 and CsI:T1; and conduction electron motilities by the “time-of flight” method with carrier lifetimes checked by optical measurements.
- Scientific Exchange Program between Latvia and USA: Support of research
visits between University of Latvia and Wake Forest University
Source: US Embassy in Copenhagen
Evaluation of Birefringence-based PTFE Film Inspection
Source: Gillette Company
The first stage of this project looked at what light scattering can
reveal about bare metal edges. The second will examine light reflected
from edges having a Teflon (PTFE) coating. The study will use several
techniques that are valuable for students to learn and will be conducted
by two graduate students.