1995 — 2001 |
Lephart, Edwin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Career: Brain Aromatase Cytochrome P-450 and Cns Development @ Brigham Young University
IBN-9507972 Lephart, Edwin D. The sex steroid hormones can be transformed from one class to another by certain enzymes. The conversion of androgens (e.g. testosterone) to estrogens by an enzyme known as aromatase cytochrome P450 plays an important role in influencing the development of the central nervous system. The dramatic impact of estrogen formation via the aromatase enzyme is responsible for structural differences between males and females in specific brain regions. These structural differences determine how the central nervous system will function along male versus female patterns for hormone secretion and the regulation of sexual behavior. This study will determine how brain estrogen biosynthesis is controlled by the aromatase gene. This will be accomplished by utilizing various molecular biological techniques. The goal of these studies is to determine the molecular basis of brain aromatase regulation by determining the regulatory elements governing how the aromatase gene is activated. To accomplish this goal, Dr. Lephart will characterize the regulatory sequences upstream of the start site of transcription for the aromatase gene and whether these elements change during development. The regulation of aromatase gene expression by androgen will be investigated and the message in brain encoding this critical enzyme will also be studied. The outcome of these studies will allow the development of a picture about how the proteins in the brain control the expression of enyzmes critical for the development of essential centers in the brain.
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0.915 |
2000 — 2003 |
Rhees, Reuben Judd, Allan Lephart, Edwin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Neuroscience Research Experiences For Undergraduates Site At Byu @ Brigham Young University
ABSTRACT Edwin Lephart DBI# 9912126
The Neuroscience Center at Brigham Young University proposes to establish a Research Experiences for Undergraduate (REU) Site in Neuroscience. Special efforts will be made to recruit students from underrepresented groups/individuals in Neuroscience and especially those from two and four year colleges in our geographical region (and throughout the U.S.) that have little or no research opportunities. Special efforts will be made to encourage women and minorities to apply. Due to the geographical location and past successful track record in supporting undergraduate research the program expects to be especially effective in reaching Native American, Hispanic, and Pacific Island students. A total of 10 students will participate in this REU site during a 10 week summer program covering Neuroscience research areas, such as, hormones and behavior, neuroanatomy, neurophysiology, electrophysiology, immunocytochemistry, molecular neurobiology, neuroimaging, and regulatory behaviors. The students will receive instruction in experimental research techniques by participating in ongoing or new research projects that require each student to present oral and written reports of their research activities. One of the major goals is to produce scientifically literate individuals having the ability to design, conduct and analyze research activities. Moreover, to have undergraduate students think critically in an integrative fashion based upon research-rich and inquiry-based research curricula (through scientific articles, literature searches and training in auxiliary research skills). As a result of this experience, the program will provide research opportunities for undergraduates in Neuroscience that will be critical in their educational training so that each student may draw upon first hand experiences that will assist them in future career choices in science.
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0.915 |
2010 |
Christensen, Merrill Lephart, Edwin Douglas |
R15Activity Code Description: Supports small-scale research projects at educational institutions that provide baccalaureate or advanced degrees for a significant number of the Nation’s research scientists but that have not been major recipients of NIH support. The goals of the program are to (1) support meritorious research, (2) expose students to research, and (3) strengthen the research environment of the institution. Awards provide limited Direct Costs, plus applicable F&A costs, for periods not to exceed 36 months. This activity code uses multi-year funding authority; however, OER approval is NOT needed prior to an IC using this activity code. |
Timing of Exposure to Selenium and Isoflavones and Prostate Cancer Prevention @ Brigham Young University
DESCRIPTION (provided by applicant): The research described in this AREA application is responsive to recommendations in the Report of the Prostate Cancer Progress Review Group (PRG). Recent data demonstrate that high selenium (Se) intake or status and high intake of phytoestrogens (isoflavones) each provide a protective effect against prostate cancer, and that their combined use may provide greater benefit than either dietary component alone. The PRG report recommends "Support studies aimed at better understanding of the roles in androgen production and in prostate physiology of nutrients such as ... selenium [and] phytoestrogens..." The objective of this work is to assess the cancer protective effects in prostate of high consumption of Se and isoflavones, individually and in combination, and to assess the critical effect of the timing of dietary exposure. Recent results from animal studies suggest that exposure begun at conception produces beneficial effects not seen when exposure is started after sexual maturation. To identify biochemical and molecular mechanisms for those effects, attention will focus on processes regulated by the androgen receptor (AR) and by NF-:B. Specific Aim 1 is to demonstrate that high dietary intake of Se and isoflavones, individually and in combination, will inhibit progression of prostate cancer in TRAMP (TRansgenic Adenocarcinoma of Mouse Prostate) mice, dependent on the timing of dietary intervention. Beginning at different time points (conception, 6, 12, and 18 weeks) and continuing to different end points (6, 12, 18 and 24 weeks), TRAMP mice will be fed diets adequate or high in Se, and low or high in isoflavones in a 2 X 2 factorial design. Measurement of body weight, genitourinary (GU) tract weight, time to palpable tumor, pathological tumor grade, and incidence of metastases will be determined for all animals sacrificed at each time point. Specific Aim 2 is to demonstrate that high dietary intake of Se and isoflavones, individually and in combination, will reduce activation of the androgen receptor (AR) and NF-:B, and decrease expression of AR- and NF-:B-regulated genes in prostates of TRAMP mice, dependent on the timing of dietary intervention. Blood levels of androgen, IGF-1, and GH will be measured by ELISAs, total Se by fluorometry, and isoflavone levels by HPLC. Se-dependent glutathione peroxidase and 5alpha-reductase activities will be assayed. AR and NF-:B activation will be determined by EMSA. Expression of AR- and NF-:B-regulated genes relevant in prostate cancer, whose expression is also modified by Se and/or isoflavones, will be examined by RT-PCR. These assays will show individual effects for each dietary component, the modifying effects each has on the other's metabolism, and the effects of combined use on the end points of interest. Correlation of these measures with time of dietary intervention and disease progression will identify the period(s) during tumor growth when supplementation may be most efficacious. This work will identify mechanisms of chemoprevention by combined consumption of different protective dietary components and the optimum time during tumorigenesis for dietary intervention. PUBLIC HEALTH RELEVANCE: This work will accomplish several objectives outlined by the Prostate Cancer Progress Review Group and by the NIH Five Year Plan "Planning for Prostate Cancer". These include 1) "defining the role of specific dietary factors in the etiology and prevention of...cancer";2) increasing "understanding of the roles in...prostate physiology of nutrients";3) definition of "the mechanisms by which these nutrients alter risk";and 4) demonstration of "the effects of nutrients on molecular events in the prostate". According to the NIH report "the effect of food constituents on molecular events in the prostate is unknown". Discovery of Se- and isoflavone-regulated genes will "identify biomarkers of the consumption of key dietary components".
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