Translational Technologies and Resources

Technologies

Biomedical and Molecular Imaging (Michael Borrelli, PhD, Director).
UAMS has a strong arsenal of research instrumentation for biomedical/molecular imaging that matches its clinical imaging capabilities. Research instrumentation includes a Bruker 7-Tesla magnetic resonance imaging (MRI) scanner, Siemens-CTI micro positron emission tomography (PET) scanner, IVIS-200 Optical Imager, VisualSonics High Resolution Ultrasonic Imager, and a GE 1.5-Tesla MRI (for larger animals). The Department of Radiology has a research cyclotron and radiochemistry laboratory that can produce unique PET and single-photon emission computed tomography (SPECT) markers and probes, which can take PET–computed tomography (CT) and PET/MRI research to levels higher than many institutions can attain. Radioisotopes from the cyclotron can also be used to label nanoparticles and their payloads to image nanoparticle distribution in the body and efficiency of payload (e.g., therapeutic agents) delivery into targeted tissues. UAMS Investigators are working with nanotechnologists at the U of A Fayetteville, to develop nanoparticles for image-guided, targeted delivery of therapeutic agents, using ionizing radiation, ultrasound, and/or lasers to trigger delivery of the therapeutics within diseased tissues.
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Experimental Pathology (Leah J. Hennings, DVM, Director).
The Experimental Pathology Laboratory provides investigators with centralized, comprehensive histological services. All services are accessed within one facility, reducing costs for investigators and the institution, increasing efficiency of sample processing, eliminating duplication of services and equipment, and maintaining stringent quality-control standards. The laboratory director, consultants, and technicians have extensive experience in histology and immunohistochemistry involving both human and animal tissues. In 2006, 63 researchers used the Experimental Pathology Core. Contact: Leah Hennings, 501-526-7624, lhennings@uams.edu
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Laboratory and Animal Medicine (Mildred Randolph, DVM, Director).
Laboratory and Animal Medicine provides animal husbandry and veterinary services for UAMS animal research. The core educates, trains, and informs the research community regarding laboratory animal science. The facilities are registered with the USDA, are covered under an Assurance with the Office of Laboratory Animal Welfare of the PHS, and are accredited by the American Association for the Assessment and Accreditation of Laboratory Animal Care.
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Skeletal Histology and Phenotyping (Larry Suva, PhD, Director). The Skeletal Histology and Phenotyping Core analyzes all aspects of muscle and bone histopathology. Decalcified bone/paraffin-embedded soft-tissue specimens are prepared by trained technologists. Methyl methacrylate processing and sectioning of specimens for histomorphometry are available. The facility also provides sophisticated single-, double-, and triple-immunohistochemical staining procedures; in situ PCR; apoptosis staining; and in situ hybridization on both paraffin- and plastic-embedded sections. In 2006, 16 individual NIH-supported investigators used the Skeletal Histology and Phenotyping Core. Contact: Larry J. Suva, 501-526-6110, suvalarryj@uams.edu
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Specialized core Facilities

Access Grid Teleconferencing Facility (Fred Bassett, Facility Operator). Over the past 6 years, the NCRR-funded Arkansas IDeA Network of Biomedical Research Excellence (INBRE) has created a teleconferencing network that utilizes Access Grid technology. Participating institutions use the studios to facilitate multi-campus meetings, teach advanced-level graduate courses (jointly via University of Arkansas, Fayetteville, and Louisiana State University), and participate in national bioinformatics conferences and presentations (e.g., monthly Virtual Seminars on Genomics and Bioinformatics, sponsored by North Dakota State University). Thus far, Access Grid studios have been established at Arkansas's major research institutions (UAMS; University of Arkansas at Little Rock; University of Arkansas, Fayetteville; University of Arkansas at Pine Bluff; and Arkansas State University). Smaller studios have been placed at 9 primarily undergraduate institutions in Arkansas, as well as the Delta Area Health Education Center. Site expansion is planned.
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Center for Distance Health (Curtis Lowery, MD, Director; Carol Ann Bynum, EdD, Director).
Housed in the College of Medicine, the Center for Distance Health (CDH) assists all UAMS specialties and disciplines by coordinating distance-health clinical/educational services, equipment and connectivity technical assistance, and telehealth-specific grant writing and research. The CDH focuses on: 1) conceptualizing/troubleshooting development of new disciplines in telehealth care and education delivery; and 2) overseeing/managing technical delivery of clinical/educational telehealth programs of all disciplines. For disciplines wishing to create a telemedicine-based system for their clinical, educational, or research ideas, the CDH offers development support in conceptualizing, troubleshooting, conducting background research, selecting equipment and connectivity, and writing grants. It also offers centralized scheduling for all telehealth activities held between UAMS and health care consumers (i.e., rural hospitals, Arkansas Department of Health, insurance companies, and individual patients).
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Metabolomics (John J. Thaden, PhD, Director). The Metabolic Assessment Core helps investigators define pathways/mechanisms that regulate aging rate and lifelong metabolic output. Analytical instruments include an HP 5890 Series IIplus gas chromatography (GC) system with a Diplomat-interfaced AOC20i/s autoinjector. GC eluents enter the positive-ion electron-impact interface of an HP5792 quadrupole MS. For liquid chromatography (LC), the Metabolic Assessment Core has an API3000 triple-quadrupole MS (Applied Biosystems/MDS-Sciex). The facility also has two HP1050 high pressure liquid chromatography (HPLC) systems with variable-wavelength and photodiode-array UV detectors (Agilent): one is equipped for chilled sampling for both DC and pulsed-electrochemical detection and cyclic voltammetry; the other, used for respirometry, measures mitochondrial and suspension-culture dissolved-oxygen consumption as well as oxygen consumption and carbon dioxide production.
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Molecular Interactions (Thomas Kieber-Emmons, PhD, Director).
A BIACORE 3000, a state-of-the-art method to defining molecular interactions between binding proteins, is available to UAMS researchers for molecular interaction analyses. The BIACORE 3000 is an optical biosensor that uses surface plasmon resonance for real-time monitoring of macromolecular interactions. Its applications include affinity measurements and binding kinetics, concentration determinations, binding-specificity analyses, and epitope mapping. BIAsimulation software (version 3.2) allows users to properly design experiments, and BIAevaluation software (version 3.2) enables researchers to analyze data and run simulations for binding-kinetics parameters.
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Musculoskeletal Imaging (Larry Suva, PhD, Director).
The Musculoskeletal Imaging Core provides quantitative measurements of body composition (including bone, muscle, and fat) and bone density, volume, architecture, and strength, as well as high-resolution bone imaging. Available technologies include soft x-ray, dual-energy x-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT), and microCT. TOP alth care and education delivery; and 2) overseeing/managing technical delivery of clinical/educational telehealth programs of all disciplines. For disciplines wishing to create a telemedicine-based system for their clinical, educational, or research ideas, the CDH offers development support in conceptualizing, troubleshooting, conducting background research, selecting equipment and connectivity, and writing grants. It also offers centralized scheduling for all telehealth activities held between UAMS and health care consumers (i.e., rural hospitals, Arkansas Department of Health, insurance companies, and individual patients).

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Nanotechnology Center at UALR (Thomas J. Walker, Director). UAMS researchers are working closely with researchers at UALR on the application of nanotechnology technology to medical issues, such as delivering individualized treatment to cancerous tumors and use of nanostructural materials for tissue and bone regeneration. The mission of the Center is to advance the science of nanotechnology through research and outreach and accelerate technological innovations into practical applications for society. The Nanotechnology Center at UALR provides access to technologies and computational resources that provide a new dimension to research opportunities on campus. The center, along with nanotechnology researchers and technology at NCTR, provides a wide range of resources for UAMS scientists working in these fields.

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Pharmacogenomics Analysis Laboratory (Fred Kadlubar, PhD, Director). Pharmacogenomics facilitates optimal treatment, dose individualization, and drug discovery, and has promise for improving treatment of most illnesses by reducing toxicity and increasing drug efficacy. The Pharmacogenomics Analysis Laboratory brings together experts in analytical chemistry, genetics, epidemiology, biostatistics, and informatics to offer researchers both consulting and analytical services. This resource will be strengthened by the recent selection of Central Arkansas Veterans Healthcare System (adjacent to UAMS) as the sole U.S. site for high throughput pharmacogenomics analysis for the national VA system. Instrumentation includes the Illumina BeadStation, Genome Analyzer, and BeadXpress. These technologies provide sequencing of DNA, miRNA, mRNA tags, and whole transcriptomes, as well as chromatin immunoprecipitation, histone methylation analyses, focused resequencing, genotyping, and measuring gene and protein expression. Patients undergoing chemotherapy or anticoagulation therapy are two large groups that could immediately benefit from this approach.

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Transgenic Mouse Production (Charles O'Brien, PhD, Director). As the number of UAMS investigators utilizing transgenic mouse models is increasing, the Transgenic Mouse Production Facility was established to meet this growing need. In addition to offering transgenic mouse production by pronuclear injection in the C57BL/6 strain of mice. The facility offers investigators access to extensive expertise in genotyping and designing/constructing transgenic and gene-targeting constructs, as well as breeding, breeding strategies, and appropriate controls for complex genetic backgrounds.
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Office of Grants and Scientific Publications (Jan Wojcik, MEd, Director). To further investigators’ research efforts, UAMS established the Office of Grants & Scientific Publications, a scientific writing resource whose mission is to increase extramural funding. The Office of Grants & Scientific Publications provides editorial/grant/manuscript preparation services to help investigators obtain extramural grant funding, publish research results in peer-reviewed biomedical journals, and prepare documents with the potential to increase grant funding and improve the health of Arkansans. The science editors on staff are grounded in biological sciences and technical writing fields; experienced in research project and consortium development; and skilled at scientific writing, document design, and document production. Editorial services emphasize polishing an investigator’s presentation of data/conclusions and ensuring that research applications are responsive to a funding agency’s goals. Staff members also train UAMS faculty/staff in grantsmanship through mentoring, lectures, workshops, and an internship program.
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UAMS BioVentures (Michael Douglas, PhD, Director).
BioVentures is the patenting/technology licensing core of UAMS with a mission to patent, license, and add value to independent investigators’ discoveries. These services are provided through its mature intellectual-property and licensing program, laboratory space for university spin-off companies, and a FDA-approved Therapeutic Production Center. Each year, BioVentures supports development and processing of around 50 new invention disclosures; manages approximately 150 patents; and completes nearly 50 agreements involving technology licensing, materials, and confidentiality. It has formed 16 companies with 8 pipeline companies in development. BioVentures also holds annual private-equity round-table meetings to bring a national risk-capital group to UAMS to view new technologies and review progress of developing translational opportunities. UAMS BioVentures actively supports entrepreneurial development of faculty/students through a graduate course (Entrepreneurial Methods for the Biomedical Scientist) and is currently working with the Kauffman Foundation to expand entrepreneurial networks in business formation/contract research support.
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Research Facilities

Bioluminescent and Fluorescent Imaging The Xenogen IVIS Imaging System is a highly sensitive CCD camera optimized for biophotonic imaging (e.g. in vitro and in vivo assays using reporter cells tagged for bioluminescence and/or fluorescence). Contact: Bill Hogue, 501-686-8911, bhogue@uams.edu
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Digital and Confocal Microscopy Laboratory This facility operates and maintains computer controlled microscope workstations capable of static and time lapse (e.g. minutes to days) imaging of living cells. Fluorescence imaging and multicolor images from fixed and living samples are generated. Microscopes are inverted and designed for analysis of living cells. However, fixed samples may be studied as well. Contact: Richard Kurten, 501-686-8269, kurtenrichardc@uams.edu
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DNA Sequencing Facility Uses a 3100 Genetic Analyzer (capillary technology) to provide DNA sequencing for plasmids and PCR products. A Qiagen cabinet is also present in the lab to provide select DNA and RNA isolation kits. Contact: Allen Gies, 501-686-6927, giesallenj@uams.edu
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Experimental Pathology Shared Resource provides centralized, comprehensive histological services, with convenient access to all services within one facility. Stringent quality control standards are maintained with GLP compliance upon request. The laboratory director, consultants, and technicians have extensive experience in routine histology and immunohistochemistry involving both human and animal tissues.  Services include: processing and embedding of tissues, frozen and paraffin-embedded tissue sections, routine staining, a wide range of special histochemical stains, immunohistochemisrty, veterinary pathology consultation, and digital slide scanning and analysis using the Aperio Scanscope.  Contact: Leah Hennings, 501-526-7624, lhennings@uams.edu
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Proteomics Facility Provides mass spectrometric analysis and identification of proteins. It is equipped with a Thermo LTQ XL linear ion trap mass spectrometer with electron transfer dissociation capability, a PerkinElmer SCIEX MALDI-prOTOF mass spectrometer, a Waters Q-Tof Micro tandem mass spectrometer and a Thermo LTQ linear ion trap mass spectrometer. Additional gel band analysis equipment includes a ProPic imaging and spot-picking robot from Genomic Solutions, a ProGest in-gel enzymatic digestion robot from Genomic Solutions, and a Bio-Rad 2D gel electrophoresis system.  Contact: Sam Mackintosh, 501-526-5978, mackintoshsamuelg@uams.edu
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Microbiology & Immunology Flow Cytometry Facilities Provide researchers with an powerful and diverse tool to measure multiple physical characteristics of individual cells in suspension. The flow cytometer can indicate relative cell size and density or complexity by measuring forward- and side-scattered laser light, respectively. In addition, the flow cytometer can measure relative fluorescence from fluorescent probes which bind to specific cell-associated molecules. Contact: Andrea Fox, 501-686-5145, afox@uams.edu
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MicroPET Facility Consists of a Siemens FOCUS MicroPET that can produce whole body or regional PET images of animals ranging in size from mice to small dogs; and can image the head and appendages of human subjects. An on-site cyclotron and a fully staffed Radiochemistry Laborotory provide a wide range of PET markers for research projects involving PET imaging. Custom PET Markers can also be developed in collaboration with the facility's staff. Contact: Director: Michael J. Borrelli, 501-526-5897, mjborelli@uams.edu Manager: Terri L. Alpe, 501-590-0457, alpeterril@uams.edu
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Protein Biomarker Identification Facility. A facility for protein biomarker identification using SELDI (surface-enhanced laser disorption/ionization), the SELDI is utilized primarily for clinical biomarker discovery, identification and validation. Contact: Larry J. Suva,  501-526-6110, suvalarryj@uams.edu
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Technology Oriented Research Projects

Antenatal and Neonatal Guidelines, Education and Learning System (ANGELS) (Curtis Lowery, MD, Director).
ANGELS is a diverse, fully complimentary, and cost-effective telehealth collaboration between UAMS and the Arkansas Department of Human Services, in partnership with the Arkansas Medical Society and the state’s rural physicians. ANGELS creates the platform for community partnerships and translational research opportunities by using telemedicine technologies to deliver the following specialty services directly to rural providers and patients throughout Arkansas:

• High-risk Obstetrical Consultations: UAMS specialists in maternal–fetal medicine consult with women with high-risk pregnancies in their hometown clinics with the support of interactive, real-time level-II ultrasounds.
• High-risk Obstetrical/Neonatal Evidence-Based Guideline Development: UAMS specialists connect with rural providers to collectively author evidence-based guidelines targeting care for Arkansas’ rural patients.
• Nursing Call Center Support: A 24/7, RN-staffed call center responds to needs of providers and patients statewide with on-the-spot triage, maternal transports, referral, scheduling, and follow-up on a toll-free line.

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Center for Distance Health (Curtis Lowery, MD, Director; Carol Ann Bynum, EdD, Director).
To strengthen evidence-based educational offerings of ANGELS/Rural Hospital Program, the CDH added teleconferences on pediatrics, childhood obesity, obstetrical nursing, and prenatal genetics to the university’s distance-education curriculum. In addition to discipline-specific teleconferences, CDH’s educational programming will be enhanced by the CDH Training Center that is being established. This on-campus center is comprised of clinical, administrative, and educational interactive video equipment designed to offer hands-on, interactive video experiences for clinicians, educators, and administrative personnel who wish to learn more about integrating translational technologies into their practices. Only in its second year of existence, the CDH directs the following grant/contract-funded service-delivery and research projects, with more projects funded by UAMS or in development.

• Correctional Telehealth: The CDH reduces inmate transports through this telemedicine-based obstetrical consultation service for prisoners with high-risk pregnancies. Telemedicine extends best practices to this high-risk community, and UAMS can study the effects of telemedicine among this unique population.
  
• School-based Telemedicine: Telehealth for Kids in Delta Schools is an in-school telemedicine and telemonitoring program that provides evidence-based pediatric health care and behavioral services to students residing in the state’s most impoverished county, which has no pediatrician.
• Telestroke: Arkansas Stroke Assistance through Virtual Emergency Support is a $4.6 million contractual project with the goal of improving stroke morality and morbidity. This evidence-based telemedicine initiative uses the Arkansas Telehealth Network and a team of neurologists to consult, triage, and recommend treatment to stroke victims.
  
• Mental Telehealth: The CDH launched this contractual service that manages point-to-point telemedicine consultations to 35 Arkansas clinics providing mental health services and substance abuse treatment.
  
• Train & Maintain: Train & Maintain trains hospitals operating bioterrorism telemedicine equipment to increase knowledge, comfort, and ability to respond in an emergency, while maintaining line connectivity and testing.

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Arkansas Telehealth Network (Curtis Lowery, MD, Director).
FCC Rural Health Care Pilot Program approved $5 million in funding for UAMS to lead a statewide, cross-institutional effort to build and operate the Arkansas Telehealth Network. The 15-member partnership of health care organizations includes state agencies, non-profit and private hospitals, community agencies, and others interested in establishing telemedicine services for their rural patient populations. This program uses the state’s telemedicine resources to create a consolidated telehealth network that benefits all Arkansans seeking medical care or education. The completed Arkansas Telehealth Network will encompass 289 clinical and educational telehealth sites, with statewide access to Internet2 and connection to 520 public schools. The extensive network of partners throughout Arkansas will facilitate research studies that pair diverse urban and rural researchers through virtual interaction, which ensures technology-infused translational research.
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Cell Differentiation and Signaling Research Program (Robert McGehee, Jr, PhD, Director).
The goal of the Cell Differentiation and Signaling Research Program is to discover how fundamental biological mechanisms control development/differentiation of both normal and tumor cells, with an emphasis on stem cell biology and cell signaling. Discoveries from these investigations will be used to develop new cancer therapeutics. Many tumors or malignancies, such as myeloma and liposarcoma, exhibit a dedifferentiated or less differentiated cellular phenotype. Because cellular differentiation is intimately related to the biology of stem cells, understanding how to isolate and utilize stem cells has the potential to significantly impact cancer biology and therapy. Specific inhibitors may be developed to effectively treat a range of cancers, and understanding fundamental signaling mechanisms may provide new insights into the mechanisms of multi-drug resistance. The center has used the proteomics cores to identify diagnostic proteins associated with prostate cancer, myeloma, and pancreatic cancer.
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Center for Addiction Research (Warren K. Bickel, PhD, Director).
The Center for Addiction Research has assembled 36 faculty and staff and more than $23 million in research support from NIH since 2004. Research projects involve translating basic behavioral/pharmacological processes into methods to enhance outcomes during treatments for substance dependence for adults and adolescents. Research efforts include 1) understanding loss of control and impulsive behavior that leads to continued drug use despite negative outcomes or leads to relapse during/after treatment; 2) examining cost effectiveness of various aspects of addiction treatment; 3) understanding parenting processes and how parent training can be used as a prevention or intervention tool to reduce substance abuse and mental health problems in children; 4) testing medications for treating drug dependence and withdrawal, including characteristics (e.g., genetics, sex, race) that may influence outcome; 5) understanding marijuana dependence to develop better methods to assist attempts to quit; and 6) examining behavioral pharmacology/abuse liability of psychoactive compounds in humans. The Center has developed and tested a computerized therapy program and demonstrated that computerized therapy has the lowest personnel cost and is as effective as therapist-delivered therapy when the same treatment is provided.
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Center for Alcohol and Drug Abuse Studies (S. Michael Owens, PhD, Director).
The Center for Alcohol and Drug Abuse Studies focuses on clinical/translational research to develop innovative monoclonal antibody-based medications for treating medical problems associated with phencyclidine-like and methamphetamine-like drugs. Investigators in this program have about $10 million in active funding from the National Institute on Drug Abuse. As part of their work in the Center for Alcohol and Drug Abuse Studies, Dr. Owens and W. Brooks Gentry, MD, have developed monoclonal antibodies against the abused drugs phencyclidine and methamphetamine. The two formed a small business (InterveXion Therapeutics) with two additional partners, Ralph Henry, PhD (Department of Biological Sciences at the University of Arkansas, Fayetteville), and Barry Holtz, PhD (Arkansas Biosciences Institute, UAMS), with the goal of translating these antibodies into medical therapies for human drug abuse.
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Center for Orthopedic Research (Larry Suva, PhD, Director).
Researchers within the Center for Orthopedic Research are focused on developing new approaches for preventing/treating osteoporosis, arthritis, and related disorders. With the Winthrop P. Rockefeller Cancer Institute, the Center for Orthopedic Research has a strong commitment to understanding the mechanisms of breast cancer metastasis to bone and is actively pursuing mass spectrometry studies to discover disease biomarkers. The technological sophistication of the bone-imaging techniques (e.g., micro-CT, quantitative CT for small animals, dual x-ray absorptiometry, and skeletal histomorphometry) employed by the Center for Orthopedic Research, coupled with scientific expertise and extensive experience in managing clinical trials, make the center unique in Arkansas. The center has designed and tested new spine-surgery screws and evaluated facial-sling material that resulted in surgery changes in the UAMS Plastic Surgery Department. The center also uses the proteomics cores to identify diagnostic proteins and was the first to study/identify biomarkers in human tears to diagnose breast cancer.
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Center for Translational Neuroscience (CTN) (Edgar Garcia-Rill, PhD, Director). The CTN facilitates/integrates UAMS research on translational aspects of neuroscience, bringing basic neuroscience findings to the bedside and contributing to clinical neuroscience. For example, CTN investigators developed a device (patented and licensed through BioVentures) that promises to alleviate excessive reflexes and plasticity in victims of spinal cord injuries. The CTN is also the research arm of the Jackson T. Stephens Spine & Neurosciences Institute. T. Glenn Pait, MD, is Director of the Spine Institute and Clinical Director of the CTN. The CTN has been funded by the NIH, NSF, and various companies and agencies and is now a Center of Biomedical Research Excellence funded by NCRR, which fosters mentoring of clinical scientists to assist them in reaching nationally competitive levels of NIH grant support.
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Muscular Dystrophy (MD) and Amyotrophic Lateral Sclerosis (ALS) Research and Clinical Center (John Crow, Ph.D., Stacy Rudnicki, MD).
ALS and MD Research and Clinical Centers are located in major medical institutions chosen by the MD Association (MDA) based on the amount of ALS research and staff expertise. While UAMS was designated an MDA clinic in 1990, we only recently received the designation as a Research and Clinical Center—one of only 33 in the country. The new designation gives patients more opportunities to participate in clinical trials for MD and ALS treatments and provides valuable training opportunities for trainees. Prior to development of the UAMS ALS clinic, area patients with ALS had to travel to St. Louis, MO, or Dallas, TX, to be seen in a multidisciplinary clinic, receive new treatments, or participate in clinical trials at a designated research center. The UAMS MD/ALS Research and Clinical Center is a conduit for translational research. For example, John Crow, PhD, and Paul Prather, PhD, both from the Department of Pharmacology and Toxicology, are conducting translational research aimed at identifying combinations of FDA-approved drugs and nutriceuticals with potential therapeutic applications for ALS.
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Myeloma Institute for Research and Therapy (Bart Barlogie, MD, PhD, Director). The members of this research program have made seminal discoveries in myeloma biology/therapy, leading to worldwide recognition as myeloma research leaders. In the past 13 years, the myeloma program has enrolled more than 3,558 patients in research protocols and performed more than 4,265 bone marrow transplants. Multiple myeloma accounts for 10% of all hematologic malignancies and is the second most frequently occurring hematologic cancer in the United States. It is the only hematologic malignancy that is commonly associated with lytic bone disease. The Myeloma Institute has two focus groups (Myeloma Growth Control, led by Bart Barlogie, MD, PhD, and Bone Marrow Microenvironment, lead by Joshua Epstein, DSc), both of which have made important discoveries in myeloma biology/therapy. The myeloma and bone program goals include enhancing understanding of multiple myeloma pathogenesis, assessing therapy consequences, and gaining comprehensive knowledge of gene /protein expression in cancer. Myeloma is usually fatal, so new treatments that extend patient quality/quantity of life are a priority. Understanding myeloma may also shed light on the biology of other cancers that metastasize to bone, such as breast cancer, prostate cancer, and lymphoma.
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