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


School of Medicine

C. Richard Chapman, Ph.D., professor in the Department of Anesthesiology and director of the Pain Research Center, is studying Pain and the Defense Response. This psychophysiology project examines the mechanisms of the emotional dimension of pain in human volunteers. To date, his research has confirmed Sokolov's theory that a coordinated sympathetic nervous system arousal response accompanies painful and otherwise threatening events. It also has shown that the physiological changes accompanying painful stimuli exert a strong influence on the accuracy of pain reports the subjects give and that there are unexpected gender differences. These findings suggest new approaches to clinical pain assessment and management.

Wesley I. Sundquist, Ph.D., professor in the Department of Biochemistry, is studying Human Immunodeficiency Virus (HIV) Budding, or how HIV escapes one infected cell in order to spread the infection. In collaboration with Myriad Pharmaceuticals, Sundquist has shown that human Tsg101, a protein that normally functions in the cellular process of vacuolar protein sorting (Vps) is recruited by the virus to facilitate budding. His research further suggests that many other viruses also may bud by appropriating the machinery normally used by the cell to form small vesicles, the Vps pathway. Sundquist is collaborating with Chris Hill, Ph.D., associate professor, and Steve Alam, Ph.D., research assistant professor, to determine the three-dimensional structures of components of the Vps pathway.

Lillian Tom-Orme, Ph.D., M.P.H., R.N., research assistant professor in the Depart-ment of Family and Preventive Medicine, is conducting an American Indian Youth Behavioral Risk Surveillance Study: Cancer Awareness Project. She will adapt and administer the National Youth Risk Surveillance Survey to American Indian youth, ages 13-19, in the Salt Lake area to identify the health needs and protective factors among them to increase cancer awareness. Risk factors to be examined include: smoking, diet and physical activity. Study results will be used to plan for the second phase of the project: an intervention to increase healthy behavior and reduce risks.

Christiane Fauron, Ph.D., research assistant professor in the Department of Human Genetics, is studying the Mitochondrial DNA of Several Plants, Including Maize, as part of the National Science Foundation's Plant Genome Project. Mitochondria help turn food into chemical energy in plant and animal cells. Although the nucleus contains the vast majority of the cell's genes, mitochondria have their own DNA, coding for proteins vital to the cell's survival. Mitochondrial protein-coding genes appear to be very similar in different types of plants; however, most of the mitochondrial DNA lies between genes, and the function of this intergenic DNA is unknown. Fauron and her collaborators at the University of Missouri and Washington University are interested in how intergenic DNA contributes to the structural and functional diversity of plants.

Brad Preston, Ph.D., an investigator in the Program in Human Molecular Biology and Genetics, and associate professor in the Department of Human Genetics, and Rob Goldsby, M.D., assistant professor in the Department of Pediatrics, are investigating Polymerase Proofreading and Carcinogenesis. Tumor development is a multi-step process involving accumulated mutations in genes that regulate cell growth and metastasis. Preston is looking at molecular mechanisms of carcinogenesis and mutation, and has studied variations in an enzyme, DNA polymerase-d, that may be involved in the process. Goldsby inactivated the DNA polymerase-d gene in mice and found they have an increased susceptibility to cancer. The researchers' observations indicate that fidelity of replication of DNA is an important determinant in spontaneous tumor development.

Don Ayer, Ph.D., investigator at Huntsman Cancer Institute and associate professor in the Department of Oncological Sciences, is studying the Role of Transcriptional Control in Human Cancers. He has discovered two new transcription factors related to the Myc proto-oncoprotein. Ayer hypothesizes that these proteins, like Myc, will control cell growth. One, termed Mlx, has a dual role as a heterodimeric partner for both a transcriptional activator and a transcriptional repressor. The other, Mondo, is a new transcriptional activator. An intriguing characteristic of both factors is their presence in the cytoplasm, rather than the nucleus, which suggests that the entry of these proteins into the nucleus must be regulated in response to physiological cues. To understand this, Ayer is dissecting the mechanism that regulates sub-cellular compartmentalization.

Adam Wilcox, Ph.D., assistant professor, and Paul D. Clayton, Ph.D., professor, both in the Department of Medical Informatics, are Evaluating Geriatric Care Teams in Ambulatory Practice. Care managers in ambulatory clinics within Intermountain Health Care facilitate patient services, such as counseling, education, compliance follow-up and community services. An information system allows multiple clinical providers-geriatricians, social workers, psychologists, physical therapists and others-access to patient records and computerized decision support. The system also provides access to community resources and governmental programs. Wilcox and Clayton are assessing the impact of this approach in terms of seniors' health outcomes, functional status, perception of the care process, cost of care and health service utilization. The evaluation is funded by the Hartford Foundation.

Morgan R. Peltier, Ph.D., instructor in the Department of Obstetrics and Gynecology, is investigating the Pathophysiology of Genital Mycoplasmosis. Ureaplasma urealyticum and Mycoplasma hominis, two of the most common pathogens isolated from the female genital tract, are thought to cause an inflammatory response in the placenta and the reproductive tract that can be detrimental to pregnancy. Peltier, in collaboration with Barry C. Cole, M.D., Nora Eccles Harrison Professor in the Department of Internal Medicine, is purifying the virulence factors of these organisms and using a rat model system to study the mechanisms underlying the associated morbidity of pregnancy.

Joseph Yost, Ph.D., professor in the Department of Oncological Sciences and an investigator at the Huntsman Cancer Institute, is researching the Genetic Basis of Left-Right Organ Asymmetry. The vertebrate body plan has highly conserved left-right asymmetries in many internal organs, including the heart, brain, lungs and viscera. Diverse laterality defects are seen in a variety of human syndromes and developmental defects. Yost plans to take a genetic approach, using the zebra fish, to research genes necessary for organ development. This small fish, whose development accurately models that of most vertebrates, is translucent during development and in the adult, providing easy access to viewing organ alignment. This study of the genetic basis of organ asymmetry will identify genes that control normal development, as well as ones that are altered in diseases.

Edward Levine, Ph.D., assistant professor in the Department of Ophthalmology and Visual Sciences, and adjunct assistant professor in the Department of Neurobiology and Anatomy, is researching Retinal Development and Regeneration, funded in part by a four-year career development award from the Research to Prevent Blindness Foundation. He is investigating the molecular mechanisms that regulate growth and differentiation in the mammalian central nervous system (CNS). He is using the retina as a model system, because it has the essential characteristics that define CNS development: multi-potential stem cells, spatial and temporal regulation of cell proliferation and differentiation, laminar organization and neuronal microcircuits. He recently discovered that two cyclin-dependent kinase inhibitor proteins, p27kip1 and p191nk4d, are key negative regulators of retinal stem cell proliferation. He is determining the genetic and biochemical interactions between these negative regulators with Chx10, a homeobox gene essential for retinal development. Understanding these interactions will be important for deriving effective stem cell replacement strategies for the treatment of retinal and CNS degenerative diseases.

Teri Jo Mauch, M.D., Ph.D., assistant professor in the Division of Pediatric Nephrology in the Department of Pediatrics, is studying Cellular and Molecular Mechanisms Underlying Patterning of the Early Kidney. The vertebrate kidney develops in three consecutive stages: the pronephros (first kidney); the mesonephros (middle kidney); and the metanephros (definitive kidney). Mauch is using cultured chick and quail embryos to investigate patterning of the pronephros, since pronephros induction represents the first conversion of undifferentiated cells to committed kidney precursors. She has identified the tissue responsible for pronephros induction-paraxial mesoderm-and is defining the molecular mechanisms involved in the process. The project is supported by the National Institutes of Health and the March of Dimes.

College of Pharmacy

Eric W. Schmidt, Ph.D., assistant professor in the Department of Medicinal Chemistry, is investigating the Biosynthesis of Natural Products from Marine Invertebrates and Symbionts. Marine organisms are the most diverse on earth, producing many potential pharmaceuticals with unique chemical constituents and biological modes of action. Despite decades of research into the chemistry of marine organisms, little is known about how the compounds are made. By understanding the biosyntheses at the genetic level, Schmidt anticipates that a better supply of potential marine pharmaceuticals will be available, new lead compounds will be discovered and new enzymatic reactions will be possible.

You Han Bae, Ph.D., professor in the Department of Pharmaceutics and Pharmaceutical Chemistry, is investigating Bioactive Polymers for Effective Islet Delivery Systems. In transplanting pancreatic islets entrapped in immunoprotecting membranes (biohybrid artificial pancreas or BAP) to reverse type 1 diabetes, low functionality and the limited life span of the islets require a large number and frequent cell reseeding. Research to improve functionality and to expand the life span of immunoprotected islets has been focused on mimicking facilitated oxygen transport in avascular tissues and stimulating the islets with macromolecular insulinotropic agents. Bae has discovered that cross-linked hemoglobin with difunctional poly(ethylene glycol) significantly promotes insulin secretion from the islets under hypoxic conditions, expands the life span and protects them from nitric oxide attacks. He also has found that polymeric conjugates of sulfonylurea compounds and glucagon-like insulinotropic peptide-1 are effective stimulants for the entrapped islets in BAP.

Dennis J. Crouch, Ph.D., research assistant professor in the Department of Pharmacology and Toxicology, and co-director of the Center for Human Toxicology, is studying Human and Animal Dose Response and Potency Assessment of Pepper Spray Products Following Topical and Aerosolized Exposure. He is developing HPLC/MS/MS methods to measure capsacian analogs in the products, since the capsacian content of commercial pepper spray products is unregulated. He also is collaborating with Garrold S. Yost, Ph.D., professor of pharmacology and toxicology, and Lynn K. Pershing, Ph.D., research associate professor of dermatology in the School of Medicine, to determine the effects of topical exposure and inhalation of the products and to the individual capsacian. Results indicate that there is extreme variability in product content; dermal response is related to capsacian analog concentration and vehicle; and brief inhalation exposures in rats cause acute respiratory injury that may persist for 48 hours.

College of Nursing

Maureen R. Keefe, Ph.D., R.N., professor, dean of the college and holder of the Louis H. Peery Presidential Endowed Chair, is testing ways of Managing Infant Irritability. In its fourth and final year, this randomized clinical trial is testing a home-based nursing intervention for irritable or "colicky" infants. Data collected from more than 150 families in Charleston, S.C., and Denver, Colo., are being analyzed to determine the effectiveness of the intervention in reducing crying, decreasing parental stress, promoting synchrony in the parent-infant interaction and enhancing the sleep/wake cycles of the infant. This information will be valuable to care providers and parents who continue to struggle with the challenge of living with an irritable infant. Funding has been provided by the National Institute for Nursing Research, National Institutes of Health.

Usha Menon, Ph.D., R.N., assistant professor of nursing, is studying Interventions to Increase Colorectal Cancer Screening. Colorectal cancer (CRC) is the third leading cause of cancer deaths in the United States. Prospective data indicate that annual fecal occult blood tests (FOBT) can decrease mortality from CRC; however, use of these tests is very low-ranging from 19-39 percent-especially among those who are 50 or older and at highest risk for developing CRC. Tailored interventions have demonstrated significant increases in mammography, which also may be effective in CRC screening. This study will compare the effectiveness of a tailored versus non-tailored intervention designed to increase the use of FOBT and sigmoidoscopy, and to determine the effect on the cognitive stage of behavior.

College of Health

Joseph J. Carlson, Ph.D., R.D., assistant professor in the Division of Foods and Nutrition, is investigating the Association of a Plant-based Food Index and a Cholesterol-saturated Fat Index with CVD Risk Factors, Serum Nutrients and Phytochemical Status in Ethnically Diverse Adults. He is comparing two indices for "heart-healthy nutrition" in relation to cardiovascular disease (CVD) risk factors and cardio-protective serum nutrients and phytochemicals in some 12,000 African-American, Hispanic and Caucasian individuals, and from the National Health & Nutrition Examination Survey. One dietary index represents the traditional exclusionary nutrition paradigm; the other, an inclusionary plant-based paradigm. His goal is to identify potential cardiovascular-related benefits of plant-based diets, independent of saturated fat and cholesterol, and to determine if there are ethnic and gender differences in CVD risk factors and serum nutrients that are explained by dietary intake. The study, a collaboration with researchers at Stanford University School of Medicine's Center for Research in Disease Prevention, is funded by a U.S.D.A. National Research Initiative grant.

Glenn E. Richardson, Ph.D., professor in the Department of Health Promotion and Education, and Philip J. Waite, Ph.D., a former doctoral student now on the Idaho State University faculty, recently completed a three-year impact study of the Efficacy of Resilience Training in the Worksite. A 35-hour resiliency training program was presented once a week over five weeks to a large government organization in Utah. Each training session was an intensive seven-hour experiential and introspective discovery of personal resilience, as well as a guide to enhancing resilient relationships. Results showed immediate and post-test improvement in resilience, locus of control, purpose in life, self-esteem, interpersonal relationships and job satisfaction. Qualitative analyses also showed an increase in job productivity.

Linda S. Ralston, Ph.D., associate professor, and Joong-won Lee, a graduate student, both in the Department of Parks, Recreation and Tourism, conducted a research study on the Influence of Signage and Proximity of Recycling Bins on the Volume of Recycling Material Generated at a Hotel. During the three-month study at the University Guest House, guests were exposed to three different recycling treatments: in-room recycling bin only, in-room recycling bin with a moral appeals sign and a central recycling bin with an in-room moral appeals sign. Results indicated that the greater the exposure of moral appeals signage, the greater the amount of recycling materials generated. Also, the more convenient the collection point, the greater the amount of recycling materials generated. These findings may impact the hospitality industry by demonstrating the value of in-room recycling bins and low-cost signage in reducing the amount of waste being diverted to community landfills.

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