SHOWCASE for Health Sciences Graduate Student Research
Tuesday, March 5, 2013 Waterfront Place Hotel
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Welcome, The WVU Office of Research and Economic Development, through support provided by the Claude Worthington Benedum Foundation, has launched an initiative to encourage innovation and commercialization through research. The initiative, titled LIINC (Linking Innovation, Industry and Commercialization), is designed to bring faculty and graduate student expertise and talent to the attention of our industry partners through networking events. This particular event focuses on health sciences research. To our industry partners, we greatly appreciate your attendance at this event and we hope this opportunity has better informed you about the research taking place at WVU. To facilitate new partnerships and future collaboration, this booklet contains brief abstracts of our graduate student and faculty research activities. We strongly encourage you to contact them to further learn about and discuss their research in greater detail. On behalf of our faculty and graduate students, we thank you for your participation and we hope you will see WVU as a trusted partner for continued collaboration. Lindsay Emery Business Development Manager of LIINC WVU Office of Research & Economic Development 304-293-0391 lindsay.emery@mail.wvu.edu Name Badge Key Blue: Industry Gold: WVU 2
GRADUATE STUDENT RESEARCH Involvement of Focal Adhesion Kinase in Matrix Organization Physiological and pathological processes such as embryonic development, wound healing, and cancer metastasis require cellular contraction to promote cell migration throughout the body. In order for a cell to contract, it needs to adhere to its microenvironment and does so through structures called focal adhesions, which are multiprotein sites that allow anchorage and transmission of internal/ external signals. A predominant protein within these adhesions is focal adhesion kinase (FAK). FAK is targeted to the focal adhesions and can activate downstream signaling pathways important in cell survival, proliferation, and migration. The study disclosed herein utilizes a 3-D cell populated collagen matrix to study cellular force generation. The disclosed method uses a system where the cells interact with themselves and the 3-D collagen matrix. The study finds that FAK is important for transmission of intracellular force to the microenvironment in 3-D culture. Fibroblasts devoid of FAK have a low basal tension and an inability to contract in the presence of an agonist without affecting myosin phosphorylation. Loss of FAK alters the ability of the fibroblasts to organize the surrounding collagen matrix. Experiments utilizing FAK inhibitors and mutants show that targeting of the protein to the focal adhesion is necessary for the generation of tension. Applications: 
Development of small molecule inhibitors to the adhesion targeting domain of FAK to inhibit cell migration
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Utilization of 3-D culture to screen potential inhibitors
Utilize 3-D matrix to study cell-cell/cell-matrix interactions and behavior
Advantages:
Can inhibit FAK function without affecting kinase activity
Understanding cell behavior in 3-D matrix is more indicative of in vivo behavior
Student: Kim Arnold kmiede@mix.wvu.edu PI: Robert Wysolmerski rwysolmerski@hsc.wvu.edu
A Biomarker Algorithm that Represents Time from Stroke Symptom Onset Accurate determination of the time when stroke symptoms begin is critical for initiating treatment of ischemic stroke (IS) and guiding clinical care thereafter. The purpose of this project was to develop a biomarker algorithm that can be a surrogate for determining time when stroke symptoms began to improve utilization of tissue plasminogen activator (tPA) and streamline appropriate secondary prevention. The disclosed method uses total RNA extracted from whole blood in Paxgene RNA tubes to identify a genomic profile associated with time from stroke symptom onset. A biomarker algorithm was developed to model the change in gene expression as a linear function of time when controlling for age.
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Applications:
Alternative way to determine the time of stroke symptom onset in a clinical setting
Improve the utilization of tPA and secondary prevention
As a marker of brain damage or physiological stress
Advantages:
Unbiased accurate determination of the time of stroke symptom onset
Quantitative assessment of brain injury
Student: Danielle Doll ddoll@mix.wvu.edu PI: Taura Barr tlbarr@hsc.wvu.edu
Pain Management Therapy with Reduced Tolerance Liabilities Opioid narcotics are still the standard for treating moderate-to-severe pain. However, long-term side effect liabilities, including tolerance, have often led to the under treatment of pain. The disclosed opioid analgesic maintains comparable pain-relieving effects to that of morphine, with reduced tolerance liabilities. The structural framework also allows for additional compounds to be synthesized and biologically tested. The disclosed scheme describes the process by which our opioid analgesic is synthesized by a readily available opioid, thebaine. In addition, this opioid analgesic can also potentially reduce other side effects associated with opioid narcotic use, including the development of dependence and addiction.
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Applications:
Moderate-to-severe pain relief with reduced tolerance liabilities
Advantages:
Reduced health care costs
Drug derived from readily available compound
Potential to reduce other side-effects (e.g., dependence, addiction, constipation, decreased respiration)
Student: Jason Healy jrhealy@hsc.wvu.edu PI: Rae Matsumoto rmatsumoto@hsc.wvu.edu
Establishing a Safe Exposure for Nano-Cerium Dioxide Exposure Nano-cerium dioxide is used as a catalyst in diesel fuel to increase combustion efficiency and therefore, decrease the large soot emissions typically associated with these engines in on- and off-road applications. Furthermore, this nanomaterial has anti-oxidant properties that are being tested to protect against the negative effects of increased free radical protection that are associated with strokes and radiation treatment. In order for the benefits of these applications to be fully realized in terms of human activities and health, a dose-response curve needs to be established to determine the toxicity and safe exposure levels for humans. By utilizing an animal model system, the effects on nanocerium dioxide exposure can be established at different time points, doses and exposure routes.
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Applications:
Diesel fuel additive increases combustion efficiency
Anti-oxidant decreases oxidative stress associated with ischemic disease
Contrast agent for medical imaging (e.g., cancer)
Advantages:
Decreased diesel emissions
Decreased consequences of stroke and heart attack
Higher resolution imaging provides earlier tumor detection
Student: Valerie Minarchick vbukowski@mix.wvu.edu PI: Tim Nurkiewicz tnurkiewicz@hsc.wvu.edu
Using a Low Cost Motion Capture System to Quantify Motor Impairment Post Stroke According to the National Stroke Association, there are currently 7 million Americans who have survived a stroke. Due to the wide variety of impairments post stroke, it is critical for health care providers to have a way of customizing rehabilitation for patients. The goal of our project is to develop software that in combination with a low cost motion capture camera would determine a patients specific motor deficits. This information could then be used by a clinician to drive personalized rehabilitation. Another application of this program is through in-home therapy. It has been shown that rehabilitation can continue to help a stroke survivor progress and regain function years after a stroke. However, due to 7
insurance constraints and the cost associated with rehabilitation, continuing in clinical therapy for years is not a likely option. Our product could be used by patients, at home, who wish to continue their rehabilitation process after traditional therapy has ended. Applications:
Providing clinicians with specific motor impairments
Home therapy for those whose insurance will no longer support traditional in-clinic rehabilitation
Advantages:
Improving stroke rehabilitation through personalized assessments
Low cost and portable
Student: Erienne Pedersen epeders1@mix.wvu.edu PI’s: Valeriya Gritsenko & Sergiy Yakovenko vgritsenko@hsc.wvu.edu seyakovenko@hsc.wvu.edu
C8-Arylguanine Modified Oligonucleotides: Identification of Novel Z-DNA Binding Proteins
Aptamers
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DNA can adopt many different conformations, but only one has a lefthanded helical structure, Z-DNA. Although Z-DNA has been implicated in carcinogenesis and other diseases due to its role in gene expression, its overall biological function remains unclear. Recently, a novel, yet small class of proteins has been identified that bind specifically to Z-DNA and are functionally related to the innate immune response. The disclosed system is a method to discover new Z-DNA binding proteins.
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The method uses novel C8-arylguanine modified oligonucleotides, to act in vitro or in cells as binding partners for Z-DNA binding proteins. These oligonucleotides provide a unique advantage because they can form Z-DNA under physiological conditions which has been, heretofore, a fundamental limitation to the isolation of additional Z-DNA binding proteins. Further, by attachment to magnetic beads, DNA:protein complexes can be easily isolated. Thus, the C8-arylguanine modified oligonucleotides can be used as an aptamer for the identification of novel Z-DNA binding proteins. Since these proteins have a role in carcinogenesis and infection, their isolation and identification will provide further insight into the biological function of Z-DNA and will provide novel therapeutic targets. Applications:
Reveal information about the biological function of Z-DNA
Provide novel drug targets for infectious/immune diseases
Yield an aptamer-based therapeutic approach to treat cancer
Advantages:
C8-Arylguanine modified oligonucleotides provide a robust aptamer that binds Z-DNA binding proteins
Z-DNA protein complexes are easily isolated for discovery of new drug targets
Rational drug designed approach
Student: Brian Train brian.train@hsc.wvu.edu PI: Peter Gannett peter.gannett@hsc.wvu.edu
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Identification of Antibody Fragments Specific for Prostate Cancer Cells Via SELEX Prostate cancer is the most-diagnosed non-skin cancer and the second leading cause of cancer-related deaths among males in the United States. Current therapeutic and detection methods are not specific for the disease. This often leads to a more aggressive recurrence after treatment and unnecessary biopsies due to false positives in detection. To address this problem, antibody fragment molecular recognition elements (MREs) that bind to a molecule on the surface of prostate cancer cells, but not benign prostate cells, have been isolated. MREs are obtained through the Selective Evolution of Ligands by Exponential Enrichment (SELEX), an iterative enrichment of a large pool of random biomolecules for those that bind to a target of interest but not closely related targets. Seven rounds of SELEX have been completed, enriching a yeast-displayed single-chain variable fragment (scFv) antibody library with an initial diversity of 109 molecules. From this process, three MREs have been identified. The MREs show a lownanomolar affinity for LNCaP cells, with one having the ability to differentiate cancerous from benign cells. Future work will determine clinical relevance with binding to ex vivo prostatic tissue. This work will produce a prostate cancer cell-specific antibody fragment useful in therapeutic targeting and specific detection. Applications: 
Specific binding to prostate cancer cells for therapeutic targeting
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Differentiation of prostate cancer cells from benign prostatic cells for disease diagnosis
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Advantages:
Improves upon current non-specific therapeutics for prostate cancer by decreasing side effects and increasing therapeutic efficacy
Improves upon current prostate cancer diagnostics which have a high false positive rate due to benign conditions or fail to identify tumors
Student: Ryan Williams rwilliams@hsc.wvu.edu PI: Letha Sooter lsooter@hsc.wvu.edu
“Excel in research, creative activity, and innovation in all disciplines.” —Goal 2, WVU 2020 Strategic Plan for the Future
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Hosted by Linking Innovation, Industry and Commercialization (LIINC) LIINC is the 2012 UEDA Awards of Excellence winner for Innovation and Entrepreneurship
For more information on LIINC, please visit the website at: http://innovation.research.wvu.edu or contact Lindsay Emery directly at lindsay.emery@mail.wvu.edu 304-293-0391
Made possible from the support of the Claude Worthington Benedum Foundation
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