Health Sciences Report Summer 2003

Research in Brief
Summaries of Selected Research Projects at the University of Utah Health Sciences Center

School of Medicine

  • Dana Carroll, Ph.D., professor and chair of the Department of Biochemistry, is Stimulating Gene Targeting with Zinc Finger Nucleases. Gene targeting, the process of replacing an existing gene with a similar DNA sequence that has been manipulated in the laboratory, provides a method to create designed mutations in experimental organisms. It also has the potential to correct human disease mutations. Carroll is working to improve the efficiency of gene targeting by cleaving the DNA at the target site using enzymes that can be directed to arbitrarily chosen genes (see pg. 5).
  • Gerald J. Gleich, M.D., professor in the Department of Dermatology, is investigating Eosinophil Granule Proteins and Their Functions. Eosinophil granules are rich in basic proteins that are toxic to parasites and normal tissues. The proteins are released during disease, especially asthma and other allergic diseases. In a project funded by the National Institute of Allergy and Infectious Diseases, Gleich and Lori Wagner, Ph.D., senior laboratory specialist, have identified five novel proteins comprising the granule. They are characterizing these proteins and searching for new molecules by analyzing the eosinophil granule proteome. They also have identified numerous novel genes specifically expressed during eosinophil development, which are potential therapeutic targets for eosinophil-associated diseases. These studies may provide new diagnostic reagents and therapies for eosinophil-associated diseases, especially allergic diseases.
  • Lor Randall, M.D., an investigator and director of the Sarcoma Service at the University’s Huntsman Cancer Institute, and assistant professor in the Department of Orthopedics, received a grant from the Orthopedic Research and Education Foundation to develop an Improved Classification System for Mesenchy-mal Tumors using gene expression profile data. Better methods for tumor classification will improve the accuracy of diagnosis for cancer patients and allow for more precise treatment regimens.
  • Tatjana Piotrowski, Ph.D., research assistant professor in the Department of Neurobiology and Anatomy, is conducting a Genetic Analysis of Sensory Lateral Line Development in Zebrafish. The lateral line consists of hair cells, which are very similar functionally and morphologically to the hair cells of the inner ear in higher vertebrates. The hair cells of the lateral line, however, are directly exposed to the environment, which makes them well-suited for the study of cell migration, cell proliferation, and pattern formation, as well as for the direct application of functional and electrophysiological assays. Piotrowski’s research focuses on identifying the genes responsible for lateral line defects in mutant zebrafish embryos. So far, she has identified 26 mutants with defects in primordial migration and patterning of sensory organs, or the function of sensory organs proper. These genetic mechanisms also may be involved in the development of higher vertebrates, due to the similarity of hair cells in the ear to lateral line hair cells.
  • Alexander Tsodikov, Ph.D., research associate professor in the Department of Oncological Sciences and director of the Biostatistics Core of the Huntsman Cancer Institute, is studying Mathematical Models of Survival in Cancer Patients. Due to substantial variability in disease development and outcomes, there is considerable debate and uncertainty as to what constitutes the best treatment for prostate tumors. Tsodikov is developing a statistical model that considers both short- and long-term survival, then will analyze post-treatment survival data obtained in part from the Utah Cancer Registry, funded by the National Cancer Institute. The research is supported by a U.S. Department of Defense grant.
  • Rajendra Kumar-Singh, Ph.D., assistant professor in the Department of Ophthalmology and Visual Sciences, and adjunct assistant professor of human genetics, is researching Gene Therapy for Retinal Degeneration. Retinitis pigmentosa (RP) is the most common cause of genetic blindness in the United States, with no available therapy. Kumar-Singh is developing gene therapy strategies to correct RP and allied disorders, such as macular degeneration, the most common cause of blindness in people over the age of 70. He is using recombinant adenovirus vectors to smuggle therapeutic genes into the diseased retina and testing these vectors for their ability to rescue retinal degeneration in naturally occurring animal models of human disease. Technologies developed during the project also can be used in the treatment of central nervous system diseases. The research is funded by the National Institutes of Health, The Foundation Fighting Blindness, and Research to Prevent Blindness.
  • L. LuAnn Minich, M.D., associate professor of pediatric cardiology in the Department of Pediatrics, is principal investigator for the Utah Pediatric Heart Network’s Trial of Steroid Use in Kawasaki Disease. The network is one of seven centers funded by the National Heart, Lung, and Blood Institute to study congenital and acquired heart disease in children. Minich is enrolling patients in a multi-center, double-blind, placebo-controlled trial to test the effectiveness of steroid therapy for the treatment of children with Kawasaki disease and to establish the safety and efficacy of adding steroids, which are not routinely used, to the treatment regimen for these patients.
  • Larry Kraiss, M.D., associate professor in the Department of Surgery’s Division of Vascular Surgery, is studying Translational Control by Endothelial Cells. Translational control describes a mechanism used by cells to decide which proteins to make under different conditions. Endothelial cells, which make up the inner lining of blood vessels, participate in the development of diverse disease processes, from atherosclerosis to sepsis syndromes. These diseases are responsible for significant surgical problems. A better understanding of the rules used by endothelial cells to decide which proteins to make under different conditions will help further knowledge of how these diseases start and may lead to future therapy.

College of Pharmacy

  • James N. Herron, Ph.D., associate professor in the Department of Pharmaceutics and Pharmaceutical Chemistry, is investigating Synthetic Peptide Vaccines for the Treatment of Lymphoma and Systemic Lupus Erythematosus (SLE). His approach is based on synthetic peptide immunogens that mimic the conformation of a unique protein expressed on the outer surface of malignant B lymphocytes found in lymphoma and pathological B lymphocytes implicated in SLE. In both cases, elimination of the pathological cells should be an effective treatment. Because vaccines stimulate the patient’s own immune system to fight the disease, complications from side effects should be reduced significantly over more conventional therapies. The project is funded in part by the National Institutes of Health and the Pharmaceutical Research and Manufacturers of America Foundation.

College of Nursing

  • Patricia Berry, Ph.D., A.P.R.N., B.C., C.H.P.N., assistant professor in the Acute and Chronic Care Nursing Division, is leading a project to Empower and Prepare Families as Advocates for End-of-Life Care in Long-term Care Settings. As the population ages, more Americans will spend their final days in nursing homes or long-term care settings, where there is a documented need to improve end-of-life care. The first phase of this study involves conducting focus groups with family members of people who have died in a Salt Lake County nursing home in the past six to 12 months. The results will be used to design an intervention to provide family members with tools and encouragement to become advocates on behalf of their ill family member. Subsequent phases of the study will test the intervention for feasibility and effectiveness.
  • Lee Ellington, Ph.D., assistant research professor in the Division of Health Promotion and Primary Care, and a clinical psychologist, is investigating the Identification of Decision-making Issues Related to Randomized Clinical Trial Participation Among Hispanics and Non-Hispanics. Despite large numbers of patients who are eligible, few Hispanics participate in random cancer clinical trials (RCT). Ellington and an interdisciplinary, multi-ethnic research team are using focus groups to examine communication among patients, their families, and oncologists. Specifically, they’re looking at similarities and differences among Hispanic and non-Hispanic participants relating to the informed consent process for RCT. The study is funded as a pilot project from the University’s Huntsman Cancer Institute’s Cancer Center Support Grant. Collaborators include: Kathi Mooney, Ph.D., professor in the divisions of acute and chronic care, and innovative models and systems, and Sara Salisbury, project coordinator, College of Nursing; Rosemary Field, A.P.R.N., University of Utah Hospitals & Clinics; Stephanie Wahab, Ph.D., and Shadi Sahami, M.P.A., H.S.A., U School of Social Work; and Maritza Arce-Laretta, A.P.R.N., community liaison.

College of Health

  • E. Wayne Askew, Ph.D., professor and director of the Division of Foods and Nutrition, is studying the Interaction of Diet and Hypoxia on Blood Oxygenation and Performance at High Altitude. He examined the influence of diets high in either carbohydrates, fat or protein, in addition to a basal diet, on blood oxygen content, oxidative stress, and performance during rest and work at a simulated altitude of 15,000 feet. Seventeen male and female volunteer test subjects ate each of the four diets in random order for five days prior to reporting to the College of Health’s Human Performance Laboratory. During tests, subjects breathed a gas mixture containing 13.4 percent oxygen to simulate high elevation, while they performed a graded treadmill test to exhaustion. Preliminary results indicate that the high carbohydrate diet was somewhat superior with respect to blood oxygen content, endurance time to exhaustion, and maximal oxygen uptake. Co-investigators were: Andrew Subudhi, Ph.D., adjunct assistant professor, and Stacie Wing, M.S., R.D., clinical instructor, Division of Foods and Nutrition; and Colin Grissom, M.D., assistant professor of respiratory, critical care, and occupational medicine, School of Medicine.
  • Lynne Durrant, Ph.D., associate professor (lecturer) in the Department of Health Education and Promotion, is part of a research team designing a Health Education Self-care Intervention for Family Caregivers Providing Care to the Elderly. The program will consist of eight to 10 weekly class sessions, each focusing on a specific topic related to promoting healthy behaviors to reduce the stress and burdens often associated with caring for a spouse or elderly person with a physical or cognitive impairment. Each class will include information dissemination, processing, and clarification, as well as social interaction and setting goals. Caregivers are at a greater risk for developing health problems because of their tendency to neglect their own needs. These risks can be minimized if preventive measures can be learned and adopted early on by the caregiver. Co-investigators are Michael Caserta, Ph.D., associate professor at the College of Nursing’s Gerontology Center, and Dawn S. Tarabochia, M.S., a doctoral student in health education and promotion.
  • David M. Compton, Ed.D., M.P.H., F.A.L.S., professor in the Department of Parks, Recreation, and Tourism, and Jennifer Piatt, M.S., C.T.R.S., project coordinator, are conducting Project GAIN (Golf: Accessible and Inclusive Networks), a research project of the National Alliance for Accessible Golf. They are examining the effects of a curriculum designed to promote full inclusion of people with disabilities in five communities: Salt Lake City, Sacramento, Chicago, Baltimore, and Phoenix. More than 250 people with disabilities and 250 without are participating at each location, where the researchers are studying changes in participants’ self-efficacy, specialization, and intentionality. The project is funded by the U.S. Golf Association Foundation and the PGA of America Foundation.
  • Lee Dibble, Ph.D., P.T., A.T.C., clinical associate professor in the Division of Physical Therapy, is researching Clinical Balance Characteristics of Persons with Parkinsonism. Although balance problems are considered a cardinal sign of Parkinson’s disease pathology, not all persons with the disease demonstrate postural instability to the degree where they fall and suffer related injuries. This study will document the performance of persons with Parkinsonism on clinical balance tests and evaluate the effectiveness of the tests in identifying those at risk for falls. Findings will assist clinicians in determining patients at risk and provide directions for appropriate interventions. The research is funded in part by the American Parkinson’s Disease Association. Jennifer Phillips, M.P.T., M.S., clinical instructor, is the co-investigator.

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