1996 |
Cooper, Cynthia L |
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. |
Drmo and Mgbg Effects On Pc12 Cells @ Truman State University
DESCRIPTION: (adapted from applicant's abstract) Methylglyoxal bis(guanylhydrazone) (MGBG) and alpha-difluoromethylornithine (DFMO) have anti-neoplastic effects on many tissues, plus antomicrobial chemotherapeutic actions. Both drugs block polyamine biosynthesis in the putrescine --> spermidine --> spermine pathway. DFMO irreversibly inhibits ornithine decarboxylase, which converts ornithine --> putrescine. MGBG functions primarily as a spermidine analog and inhibits the S-adenosylmethionine decarboxylase required for the conversion of spermidine --> spermine. The polyamines (spermine, spermidine, putrescine) function in the cell to stabilize nucleic acids and are essential for cell viability. Recent studies implicate polyamines in control of exocytosis in some cells. The main hypotheses of the grant are that 1] polyamines are required for exocytosis of norepinephrine (NE) from adrenal medulla; 2] DFMO and MGBG interfere with exocytosis; and 3] DFMO and MGBG can be used to understand the role of polyamines in regulated exocytosis, synthesis, and uptake of catecholamines in PC12 cells (cultured adrenal medullary pheochromocytoma). [3H]NE uptake will be used as a marker for catecholamine uptake and release. Exocytosis will be stimulated by KCl depolarization, plus nicotinic, muscarinic and mixed cholinergic agonists. Digitonin-permeabilized cells will be used to examine the role of Ca++ in release. High performance liquid chromatography (HPLC) will be used to quantify endogenous polyamines, NE, dopamine (DA) and adenine nucleotides from extracted PC12 cells, after treatments with cytostatic and cytotoxic doses of one or both drugs. The data will increase the understanding of the use of these drugs as antineoplastic and antimicrobial (anti-trypanosomes) agents.
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0.931 |
2005 — 2007 |
Cooper, Cynthia D |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Regulation of Neural Crest Cell Fate by Foxd3 @ University of Washington
DESCRIPTION (provided by applicant): Arising early during development, the neural crest consists of a homogenous population of cells that give rise to a variety of cell types, including pigment cells, cartilage and neurons of the peripheral nervous system. It is known this specification process, as well as survival of the resulting cell lineages, rely on precise regulation of environmental cues and transcriptional networks, yet many of the molecular mechanisms remain unclear. We propose to examine the role of the transcriptional repressor, foxd3, in neural crest specification and subsequent maintenance of the neural crest derived melanocyte lineage. Mitfa expression is necessary and sufficient for the specification of melanophores, one of three types of pigment cells derived from zebrafish Danio rerio neural crest. We hypothesize that foxd3 regulates mitfa expression and interacts with the c-kit signaling pathway to control neural crest specification and maintenance of the melanophore lineage. Elucidating the regulation of mitfa and melanophore differentiation may provide insight into mechanisms underlying pigment cell disorders such as neurofibromatosis and melanoma.
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0.947 |
2021 |
Cooper, Cynthia D |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Function of Albinism Gene Oca2 in Non-Melanocyte Cell Development @ Washington State University
Project summary Loss of function mutations in the oculocutaneous albinism 2 (oca2) gene not only lead to defects in black pigment (melanin) synthesis important for skin color, but also increase the chances of developing ?side? or ?pleiotropic? effects. Some examples of pleiotropic effects include deficiencies in sensory or neural system development, as well as embryonic death depending on the identity of the mutated gene. Although pleiotropic effects are commonly observed in humans with hypopigmentation disorders like Waardenburg Syndrome and albinism, the underlying mechanisms are poorly understood primarily due to low sample size. Because pigment cells are easily viewed through transparent skin and eggs can be collected in high numbers year round, we propose to use zebrafish silver cells to better understand how pleiotropic effects arise. When oca2 is mutated, zebrafish larvae continue to make the correct number of black pigment cells, melanocytes, but melanin synthesis is severely decreased. Conversely, silver pigment cells do not express oca2, but are increased in number at stages following specification from neural crest. Using oca2 mutant iridophores as a model, we will address the following R03 specific aims: 1) Determine the iridophore developmental stages impacted by oca2 function. With aim 1 experiments, we will retest the role of oca2 in iridophore specification and examine iridophore development at multiple, additional stages including proliferation, differentiation and survival ? all cellular events that could impact cell number; 2) Determine if oca2 directly or indirectly regulates iridophore number. Using our unique collection of melanocyte mutants, we will determine if oca2 directly (cell-autonomously) or indirectly (non- cell autonomously) regulates iridophore development. In additional experiments, we will conduct pilot [bulk and single cell RNA-Seq] analysis to determine if these methods can provide insight into oca2?s autonomous versus non-autonomous role during iridophore development. Specifically, these RNA-seq data will be analyzed to determine whether changes in the expression of intrinsic or extrinsic genes important for iridophore development occur with oca2 loss of function. Once these experiments are complete, we will have a characterized model for testing oca2 function in pleiotropic effects and a substantial amount of preliminary data for formulating hypotheses appropriate for R01 level research aimed at elucidating mechanistic connections between melanocytes/melanin and hearing/visual/skin system development in humans.
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0.958 |