Grant number: 1G20RR021376-01
PI Name:  SMITH, M SUSAN.
PI Email:  smithsu@ohsu.edu 
PI Title:  ASSOCIATE PROFESSOR OF PHYSIOLOGY
Project Title:  A BSL3 Facility for AIDS-Related Research
$640,000

Abstract: DESCRIPTION (provided by applicant): The Oregon National Primate Research Center (ONPRC) seeks funds to complete the second phase of a two-phase process of converting the Kroc quarantine building (Kroc) to an ABSL 3 facility. This facility will be used for Acquired Immune Deficiency Syndrome (AIDS)-related research using pathogens with aerosol transmission potential and for international quarantine of imported nonhuman primates (NHPs). Our longterm objectives are to: 1) provide ABSL 3 NHP housing facilities suitable for AIDS-related research; 2) protect immunodeficient NHPs used in other AIDS-related research; and 3) improve facilities for international quarantine of imported NHPs. The Kroc quarantine facility has been designated for international quarantine and ABSL 3 projects. The first phase of converting the Kroc to an ABSL 3 facility was completed August 2003. The second phase, requested in this application, will be accomplished with two specific aims. Specific Aim 1 proposes to purchase fixed and movable equipment for inclusion in the Kroc ABSL 3 facility (i.e., a pass-thru autoclave, redundant HVAC supply and exhaust equipment, an effluent kill tank, a downdraft necropsy table, a biosafety cabinet, a portable radiograph machine, an automatic x-ray film processor, and other miscellaneous equipment). Specific Aim 2 proposes alterations and renovations of the Kroc with installation of the purchased equipment to complete the conversion to an ABSL 3 facility.

Thesaurus Terms: AIDS, animal colony, biomedical equipment purchase, biomedical facility, building /facility design /renovation, veterinary science HIV infection, animal care, communicable disease control, isolation /quarantine Primate 

IInstitution: OREGON HEALTH & SCIENCE UNIVERSITY
PORTLAND, OR 972393098
Fiscal Year: 2005
Department: PHYSIOLOGY AND PHARMACOLOGY
Project Start: 16-MAY-2005
Project End: 31-MAY-2007
ICD: NATIONAL CENTER FOR RESEARCH RESOURCES
IRG: STRB

Grant number: 1R13RR021809-01

PI Name: AXTHELM, MICHAEL K.
PI Email: axthelmm@ohsu.edu
PI Title: ASSOCIATE SCIENTIST
Project Title: 23rd Annual Symposium on Nonhuman Primate Model for AIDS
$71,286

Abstract: DESCRIPTION (provided by applicant): This conference grant (R13) application request funds to partially cover the cost of planning, organizing, publicizing and hosting the 23rd Annual Symposium on Nonhuman Primate Models for AIDS. The Symposium will be hosted by the Oregon National Primate Research Center (ONPRC), Oregon Health & Science University (OHSU), and will be held September 21-24, 2005 at the Hilton Portland & Executive Tower in Portland, OR. This meeting has become the premier forum for the presentation and exchange of the most recent advances in AIDS research utilizing animal models. It is anticipated that approximately 275 scientists from around the world will attend this meeting. The latest findings in primate pathogenesis, immunology, virology, vaccines and therapeutics and genomics will be presented. Five consecutive half-day scientific sessions will be held, each devoted to a different discipline. Each session will have an invited Chair, who will give a 25-minute presentation to open the first half of the session, a co-Chair, who will moderate the session and entertain questions, and an invited speaker, who will also give a 25-minute talk to open the second half of the session. A Scientific Program Committee consisting of twelve members representing a broad spectrum of institutions will review abstracts and assign oral or poster presentation for each of the scientific sessions. Criteria for selection will include relevance of the topic to the theme of the meeting and the originality and quality of the information contained in the abstract. Those individuals giving formal presentations will be asked to submit their presentations in manuscript form for publication in the Journal of Medical Primatology. In addition, there will also be poster sessions for those meritorious presentations that cannot be accommodated in one of the five platform sessions. The conference will include an opening day welcome reception, a second day poster session reception and a banquet on the third day of the symposium. To further the educational mission of the meeting, an Outreach Session, primarily aimed at high school science teachers, will be held. This event will be hosted with the assistance of the Northwest Association for Biomedical Research, and the OHSU Office of Science Education Opportunities, which is dedicated to promoting public understanding of the implications and applications of the process of biomedical research.

Thesaurus Terms: AIDS, Lentivirus, Primate, disease /disorder model, meeting /conference /symposium, microbiology human immunodeficiency virus, simian immunodeficiency virus travel

Institution: OREGON HEALTH & SCIENCE UNIVERSITY
PORTLAND, OR 972393098
Fiscal Year: 2005
Department: MOLECULAR MICROBIOLOGY AND IMMUNOLOGY
Project Start: 01-JUL-2005
Project End: 30-JUN-2006
ICD: NATIONAL CENTER FOR RESEARCH RESOURCES
IRG: ZRR1

Grant Number: 1R21HD050798-01
PI Name: OJEDA, SERGIO R.
PI Email: ojedas@ohsu.edu
PI Title: SCIENTIST/DIVISION HEAD
Project Title: A Novel Gene Network Controlling Mammalian Puberty
$165,176

Abstract: DESCRIPTION (provided by applicant): Much has been learned in recent years about the central mechanisms controlling the initiation of mammalian puberty, it is now clear that no isolated pathway or cellular subset is responsible for this control, which instead appears to be exerted by regulatory gene networks. A global approach for the system-level identification of such networks has never been attempted, essentially due to the lack of appropriate technology, and the relative paucity of genetic and biochemical details that can be assimilated into a testable biological model. The emergence of high-throughout approaches and novel computational methods for data analysis is giving us for the first time the opportunity of identifying genetic modules involved in the hierarchical control of puberty. Using some of these approaches we have singled out a group of genes that may represent the first identified genetic network involved in the neuroendocrine control of female puberty. These genes share the feature of having been earlier identified as involved in "tumor suppression". In this application, prepared in response to PA Number PA-03-079, we propose to combine emerging technology to develop the novel concept that "tumor suppressor genes" (TSGs) form a functionally interactive network that - operating within neuronal and glial subsets of the hypothalamus - provide the system-wide control underlying the pubertal activation of LHRH secretion. The following aims are proposed: 1. To construct a fist-stage architectural model of the TSG genetic network, and identify the cellular sites of expression of both upper echelon genes and genes situated at nodal points in the network. To achieve the first part of the aim we will test novel computational methods not yet applied to the dissection of complex biological processes in mammals; the second part will be accomplished using immunohistochemistry-/n situ hybridization procedures. 2. To experimentally test the viability of the TSG network via perturbation of in silico predicted key components of the system. We propose to achieve this aim by disrupting TSG expression using the technology of small-interfering RNAs (siRNA) delivered to the hypothalamus via the novel approach of modified lentiviruses carrying dual siRNA transcriptional cassettes. Although siRNAs are widely used to perturb gene expression in mammalian cells, the methodology to achieve long-term silencing effects in vivo is still in its infancy.

Thesaurus Terms: animal puberty, genetic model, hypothalamus, model design /development, tumor suppressor gene computational biology, gene expression, small interfering RNA immunocytochemistry, in situ hybridization, laboratory rat

Institution: OREGON HEALTH & SCIENCE UNIVERSITY
PORTLAND, OR 972393098
Fiscal Year: 2005
Department: PHYSIOLOGY AND PHARMACOLOGY
Project Start: 25-JUL-2005
Project End: 30-JUN-2007
ICD: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
IRG: ICER



Grant Number: 2M01RR000334-39
PI Name: DORSA, DANIEL
PI Email: dorsad@ohsu.edu
PI Title: PROFESSOR
Project Title: GENERAL CLINICAL RESEARCH CENTER
$5,340,000

Abstract: This abstract is not available.

Thesaurus Terms: There are no thesaurus terms on file for this project.

Institution: OREGON HEALTH & SCIENCE UNIVERSITY
PORTLAND, OR 972393098
Fiscal Year: 2005
Department: MEDICINE
Project Start: 06-MAR-1997
Project End: 30-NOV-2009
ICD: NATIONAL CENTER FOR RESEARCH RESOURCES
IRG: RIRG



Grant Number: 2R01HD006159-31A1
PI Name: NOVY, MILES J.
PI Email: gibbinsc@ohsu.edu
PI Title: SENIOR SCIENTIST
Project Title: Preterm Labor and Fetal Sequelae: Role of Ureaplasmas
$372,098

Abstract: DESCRIPTION (provided by applicant): The objectives of this Research Plan are to assess the efficacy of antibiotic and anti-inflammatory therapy on preterm labor and relevant sequelae of prematurity (i.e., fetal lung injury) in mobile, chronically catheterized pregnant rhesus monkeys infected intraamniotically with Ureaplasma parvum (formerly U. urealyticum serovar 1). It is our hypothesis that prenatal treatment of intrauterine ureaplasmal infection with an intravenous macrolide antibiotic combined with an anti-inflammatory agent and an immunomodulator will inhibit preterm labor, delay premature delivery, and ameliorate or prevent fetal/neonatal lung disease Physiological studies together with cellular and molecular studies of intrauterine and fetal tissues will address the following questions: (1) Does therapy with azithromycin combined with a prostaglandin synthesis inhibitor (indomethacin) and with dexamethasone inhibit intraamniotic microbial growth and downregulate the cytokine/prostaglandin cascade? (2) Do these interventions prevent preterm labor and fetal lung disease without adverse fetal side-effects? The effect of no treatment, antibiotic therapy, and combined antibiotic/anti-inflammatory therapy on preterm labor and fetal sequelae will be compared. A number of endpoints will be ascertained to establish links among ureaplasma infections, preterm labor, fetal lung injury and the response to therapy including potential fetal side-effects (e.g., intraventricular hemorrhage, enterocolitis). Continuous recordings of uterine contractility will be correlated with amniotic fluid levels of prostaglandins, cytokines, leukocytes, MMPs and maternal, fetal and amniotic fluid levels of azithromycin. Quantitative cultures and PCR for ureaplasmas will be performed on amniotic fluid, blood and fetal tissues. Tissue cytokine mRNA will be quantitated by real-time PCR. Fetal lung damage will be assessed by histopathologic and immunohistochemical methods and by lung morphometry. The gastrointestinal tract, meninges and brain will be examined for inflammation. Death of oligodendrocyte progenitors and other cell types in cerebral white matter will be evaluated by immunohistochemical methods and assays for apoptosis. The work proposed is unique in its use of combined interventional strategies in a well established nonhuman primate model of intrauterine infection. The results should illuminate the causal role of ureaplasma in prematurity and lead to advances in clinical management.

Thesaurus Terms: Mycoplasmatales, antiinflammatory agent, birth, combination chemotherapy, embryo /fetus disorder, immunomodulator, macrolide antibiotic, nonhuman therapy evaluation, pregnancy disorder chemotherapy, pregnancy infection, premature labor azithromycin, dexamethasone, disease /disorder prevention /control, embryo /fetus drug adverse effect, indomethacin, lung disorder, premature infant animal Macaca mulatta, enzyme linked immunosorbent assay, female, immunocytochemistry, polymerase chain reaction, western blotting

Institution: OREGON HEALTH & SCIENCE UNIVERSITY
PORTLAND, OR 972393098
Fiscal Year: 2005
Department: OBSTETRICS AND GYNECOLOGY
Project Start: 01-JAN-1979
Project End: 31-MAY-2009
ICD: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
IRG: PN



Grant Number: 2R01NS037952-05A2
PI Name: SIMERLY, RICHARD B.
PI Email: rsimerly@chla.usc.edu
PI Title: DIRECTOR, NEUROSCIENCE PROGRAM
Project Title: Development of Sexually Dimorphic Forebrian Pathways
$330,919

Abstract: DESCRIPTION (provided by applicant): The long-range goal of this work is to clarify cellular mechanisms that underlie development of sexually dimorphic neural pathways in the mammalian forebrain. The proposed project will use a sexually dimorphic limbic-hypothalamic pathway as a model system to study how sex steroid hormones specify patterns of forebrain connections. During the second week of life, the anteroventral periventricular nucleus of the preoptic region (AVPV) receives a sexually dimorphic input from the principal nucleus of the bed nuclei of the stria terminalis (BSTp) that develops according to a directed mechanism. During the past project period we developed an organotypic co-culture model to demonstrate that sexual differentiation of this pathway is due to a target dependent, estrogen receptor alpha (ERalpha)-mediated, action of estrogen on the AVPV. Preliminary evidence presented in the body of this application indicates that the estrogen-regulated neurotrophin BDNF (brain derived neurotrophic factor), and the class 3 semaphorin Sema 3C, are expressed in the AVPV in sexually dimorphic patterns and appear to play important roles in promoting BSTp-AVPV projections. Our Overall Hypothesis is that E2 acts on the AVPV during the first few days of life to alter expression of neurotrophic and chemotropic factors that promote its innervation by BSTp neurons. Both in vitro and in vivo experimental models will be used to test two specific hypotheses: Specific Aim 1. During postnatal development, ERalpha mediates increased expression of BDNF in the AVPV, which acts on BSTp axons via TrkB receptors to promote neurite extension. Specific Aim 2. ERalpha dependent expression of semaphorin in the AVPV influences development of sexually dimorphic projections from the BSTp to the AVPV. In addition to characterizing expression of these molecules during development of the BSTp-AVPV pathway, we will utilize a loss of function/gain of function strategy to explore their role during growth and guidance of BSTp projections. The results of these studies will make a significant contribution to our emerging understanding of molecular events that mediate hormonal control of brain development, and will add to what is known about developmental regulation of axon guidance generally. These studies may also provide clues about mechanisms responsible for sex-linked aberrations in neural connectivity that contribute to a variety of hormone-sensitive neurological disorders.

Thesaurus Terms: brain /spinal pathway /tract, brain derived neurotrophic factor, developmental neurobiology, preoptic area, protein signal sequence, sex differentiation, thalamus estradiol, estrogen receptor, gender difference, gene expression, growth factor receptor, hormone regulation /control mechanism, protein localization, receptor expression genetically modified animal, immunocytochemistry, in situ hybridization, laboratory mouse, mixed tissue /cell culture, newborn animal, polymerase chain reaction

Institution: OREGON HEALTH & SCIENCE UNIVERSITY
PORTLAND, OR 972393098
Fiscal Year: 2005
Department: CELL AND DEVELOPMENTAL BIOLOGY
Project Start: 01-SEP-1999
Project End: 08-AUG-2005
ICD: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
IRG: NNB



Grant Number: 7U01AA013510-05
PI Name: GRANT, KATHLEEN A.
PI Email: grantka@ohsu.edu
PI Title: PROFESSOR
Project Title: INIA: Stress and Ethanol Self-Administration in Monkeys
$104,867

Abstract: DESCRIPTION (provided by applicant): Stress is believed to be an etiological factor in the abuse of ethanol. Chronic and acute stress are known to alter the behavioral effects of ethanol, including the reinforcing effects. Available evidence also suggests that chronic stress alters neurotransmission in specific brain regions that are important for mediating the reinforcing effects of many drugs of abuse, including ethanol. However, there is a need to more completely characterize the limbic, hypothalamic, pituitary and adrenal response to stress an how this response predicts heavy ethanol self-administration. In addition, the source of stress can determine the endocrine and nervous systems response and adaptation. Macaque monkeys are social animals and form stable, liner, social dominance hierarchies. The relative rank of an individual within social hierarchies has trait-like qualities and remains constant, even if the monkeys are separated for some time. Many studies have shown that social subordination in macaque troops results in elevated signs of stress. Socially-derived stress in monkeys can be categorized as psychogenic and, in subordinate monkeys, uncontrollable. Stress of this nature is most associated with stress-induced psychiatric pathology, including alcoholism. We propose to investigate the effects of socially-derived stress, specifically social subordination and limited social contact on ethanol self-administration. We have developed a model of alcohol self-administration in macaque monkeys that produces excessive ethanol? consumption in a proportion of the population. The heavy drinkers are largely male and consume an average of 3.0-4. 0 g/kg/day (I 2-16 drinks/day) with average blood ethanol concentrations of 160 mg% 8 hours into the daily drinking episode. With this model we propose to characterize the limbic, hypothalamic, pituitary and adrenal response to stress in naive monkeys and then explore how this response predicts heavy ethanol self-administration.

Thesaurus Terms: alcoholic beverage consumption, self medication, social dominance, social status, stress, substance abuse related behavior alcoholism /alcohol abuse, behavior prediction, behavioral genetics, cooperative study, endocrinology, ethology, gene expression, hypothalamic pituitary adrenal axis, immune system, isolation /deprivation, limbic system, reinforcer, social psychology, socioenvironment Macaca, behavioral /social science research tag, microarray technology, phlebotomy

Institution: OREGON HEALTH & SCIENCE UNIVERSITY
PORTLAND, OR 972393098
Fiscal Year: 2005
Department: BEHAVIORAL NEUROSCIENCE
Project Start: 01-FEB-2002
Project End: 31-DEC-2006
ICD: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
IRG: ZAA1