Jiang-Fan Chen - US grants
Affiliations: | Boston University, Boston, MA, United States |
Area:
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The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, Jiang-Fan Chen is the likely recipient of the following grants.Years | Recipients | Code | Title / Keywords | Matching score |
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2001 — 2005 | Chen, Jiang-Fan | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Novel Benefit of A2a Receptor Inactivation in Pd Models @ Boston University Medical Campus DESCRIPTION: (Adapted from the Applicant's Abstract) Parkinson's disease patients experience profound depletion of striatal dopamine (DA) due to degeneration of the nigrostriatal DA pathway. The predominant treatment for the past 30 years has been the DA precursor, L-dopa. While this strategy improves motor deficits, it has no effect on the underlying degenerative process, and indeed can have the additional unwanted side-effect of inducing dyskinesia. A possible alternative therapy, with neuroprotective ability appears to be use of antagonists of a specific class of adenosine receptors, A2A. These agents appear to have both motor-activating properties and preliminary data suggest they may also attenuate MPTP-induced DA neurotoxicity and prevent the locomotor stimulation that occurs with chronic DA receptor stimulation. The proposed studies will systematically investigate the novel motor and neuroprotective effects of A2A receptor antagonists. Methods center around pharmacological studies and use of genetic knockout (KO) approaches. There are three specific aims: 1) to test the hypothesis that A2A inactivation enhances motor function through D2R-dependent and independent mechanisms using A2AR-KO, D2R-KO and double KO mice; 2) to test the hypothesis that A2AR inactivation prevents the development of chronic L-dopa-induced rotational motor sensitization in unilateral 6-OHDA-lesioned mice; and 3) to characterize the role of V in MPTP-induced neurotoxicity by establishing the potency, "therapeutic window" and by "analyzing synergy between A2AR activation and inactivation;" in addition, the effect of A2AR agents on MPTP metabolism in vivo and in cell culture will also be examined to investigate the neurochemical mechanisms of protection by A2AR inactivation. |
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2004 | Chen, Jiang-Fan | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Bioinformatics /Molecular Ident. /Cis Elements /Dopamine @ Boston University Medical Campus DESCRIPTION (provided by applicant): Dopamine is an important neurotransmitter in CNS and contributes profoundly to a variety of motor and emotional behaviors. Dopaminergic dysfunction has been associated with several major neuropsychiatric disorders, ranging from drug addiction to schizophrenia to Parkinson's disease. Molecular studies of dopamine function have revealed a set of Dopamine-Regulated Genes (DRGs), which contribute critically to the unique neurochemical and behavioral properties of the striatum. The central hypothesis of this proposal is that these DRGs are co-regulated by a common but complex set of cis-elements and transcription factors. Our primary goal is to identify and validate the clusters of cis-elements for DRG expression (CEDRG) using integrated molecular and bioinformatics approaches. Specific Aim 1: We will employ a set of bioinformatics and molecular analysis tools to characterize as fully as possible the genomic organization of the DRGs, with particular effort to determine the TSSs of DRG. We will integrate all genomic information for DRGs into a Web-accessible database, DopamineDB, which will provide a unique resource for investigation of dopamine neurobiology. Specific Aim 2: Following phylogenetic analysis of human and mouse DRGs to reveal evolutionally conserved regions within their promoters, we will employ a range of statistical model-based algorithms (Clover [1]) and Glam [2]) to identify statistically over-represented cis-Elements for Dopamine-Regulated Gene expression (CEDRG). We will systematically evaluate the predicted known and novel cis-element binding activity by ChIP-chip analysis and gel shift assay, respectively, in the putative proximal DRG promoters. Specific Aim 3: We will determine functional interactions of CEDRGs by detecting statistically significant CEDRG clusters, and by assaying transcription activity of CEDRG clusters in a striatal cloned cell line (ST14A). Furthermore, we will employ a "safe-haven" transgenic strategy to evaluate in vivo function of identified CEDRG in transgenic mice. Finally, we will examine DRG expression in mice deficient in transcription factors corresponding to the CEDRG to conclusively determine their involvement in DRG expression. The molecular and bioinformatics analyses are integrated throughout the project to overcome major limitations of each individual technique. The information derived from systematic analyses of DRGs will provide critical insights into dopamine functions and identify novel dopamine-regulated transcription factors and thus greatly facilitate the development of novel treatment strategies for dopamine-associated neuropsychiatric disorders such as drug addiction. |
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2005 — 2006 | Chen, Jiang-Fan | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Crcns-Bioinformatics &Ident.:Cis-Elements: Da Receptors @ Boston University Medical Campus DESCRIPTION (provided by applicant): Dopamine is an important neurotransmitter in CNS and contributes profoundly to a variety of motor and emotional behaviors. Dopaminergic dysfunction has been associated with several major neuropsychiatric disorders, ranging from drug addiction to schizophrenia to Parkinson's disease. Molecular studies of dopamine function have revealed a set of Dopamine-Regulated Genes (DRGs), which contribute critically to the unique neurochemical and behavioral properties of the striatum. The central hypothesis of this proposal is that these DRGs are co-regulated by a common but complex set of cis-elements and transcription factors. Our primary goal is to identify and validate the clusters of cis-elements for DRG expression (CEDRG) using integrated molecular and bioinformatics approaches. Specific Aim 1: We will employ a set of bioinformatics and molecular analysis tools to characterize as fully as possible the genomic organization of the DRGs, with particular effort to determine the TSSs of DRG. We will integrate all genomic information for DRGs into a Web-accessible database, DopamineDB, which will provide a unique resource for investigation of dopamine neurobiology. Specific Aim 2: Following phylogenetic analysis of human and mouse DRGs to reveal evolutionally conserved regions within their promoters, we will employ a range of statistical model-based algorithms (Clover [1]) and Glam [2]) to identify statistically over-represented cis-Elements for Dopamine-Regulated Gene expression (CEDRG). We will systematically evaluate the predicted known and novel cis-element binding activity by ChIP-chip analysis and gel shift assay, respectively, in the putative proximal DRG promoters. Specific Aim 3: We will determine functional interactions of CEDRGs by detecting statistically significant CEDRG clusters, and by assaying transcription activity of CEDRG clusters in a striatal cloned cell line (ST14A). Furthermore, we will employ a "safe-haven" transgenic strategy to evaluate in vivo function of identified CEDRG in transgenic mice. Finally, we will examine DRG expression in mice deficient in transcription factors corresponding to the CEDRG to conclusively determine their involvement in DRG expression. The molecular and bioinformatics analyses are integrated throughout the project to overcome major limitations of each individual technique. The information derived from systematic analyses of DRGs will provide critical insights into dopamine functions and identify novel dopamine-regulated transcription factors and thus greatly facilitate the development of novel treatment strategies for dopamine-associated neuropsychiatric disorders such as drug addiction. |
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2005 — 2009 | Chen, Jiang-Fan | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
A1/A2a Receptors and Caffeine Psychostimulation @ Boston University Medical Campus Caffeine is the most widely consumed psychoactive substance. It is estimated that caffeine consumption from all sources averages approximately 70 mg/person/day worldwide and -220 mg/day/person in the US and Canada. Moderate consumption of caffeine produces overall psychostimulant effects (reducing fatigue, enhancing performance) in humans with little risk of harmful side effects. Caffeine is known to act at a multitude of molecular targets. Therefore, depending on dose, caffeine can produce many different effects in the intact organism. Presently, caffeine is believed to exert its effects primarily by blocking brain adenosine, particularly AI and A2A receptors. However, the evidence is circumstantial and the possible contribution of other molecular targets, particularly in the untoward effects of higher doses, remains to be determined. The overall goal of the proposed studies is to conclusively assess the contribution of the AI and A2A receptors and of the central versus peripheral Aj/AaA receptors to caffeine's psychostimulant and cardiovascular effects in mature and developing animals. This proposal is built on our successful development of two novel adenosine receptor knockout models: the congenic Ai-A2A receptor double knockout and a conditional, tissue-specific A2A receptor knockout mouse. With these novel knockout models coupled with molecular, neurochemical and pharmacological analyses, we will test the hypotheses that: (1) forebrain A2A receptors are essential for the psychostimulant properties of caffeine, and combined blockade of AI and A2A receptors mediate most effects of caffeine in adult animals; (2) both AI and A2A receptors contribute to the cardiovascular response to acute caffeine, and (3) the short and long-term effects of caffeine on immature animals are distinct from effects in adults and are mediated by different molecular targets. The information derived from these studies will provide the clearest assessment yet of the role of subtypes of adenosine receptors in mediating caffeine's psychostimulant effect. This will also shed light on the long-term effects of perinatal caffeine exposure, which may have significant public health relevance. This knowledge will significantly enhance our understanding of caffeine's psychostimulant action, and provide a neurobiological basis for guidelines for healthy usage of caffeine as a stimulant to improve human performance. |
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2007 — 2008 | Chen, Jiang-Fan | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Bioinformatics &Identification of Cis Elements For Dopamine Gene Expression @ Boston University Medical Campus DESCRIPTION (provided by applicant): Dopamine is an important neurotransmitter in CNS and contributes profoundly to a variety of motor and emotional behaviors. Dopaminergic dysfunction has been associated with several major neuropsychiatric disorders, ranging from drug addiction to schizophrenia to Parkinson's disease. Molecular studies of dopamine function have revealed a set of Dopamine-Regulated Genes (DRGs), which contribute critically to the unique neurochemical and behavioral properties of the striatum. The central hypothesis of this proposal is that these DRGs are co-regulated by a common but complex set of cis-elements and transcription factors. Our primary goal is to identify and validate the clusters of cis-elements for DRG expression (CEDRG) using integrated molecular and bioinformatics approaches. Specific Aim 1: We will employ a set of bioinformatics and molecular analysis tools to characterize as fully as possible the genomic organization of the DRGs, with particular effort to determine the TSSs of DRG. We will integrate all genomic information for DRGs into a Web-accessible database, DopamineDB, which will provide a unique resource for investigation of dopamine neurobiology. Specific Aim 2: Following phylogenetic analysis of human and mouse DRGs to reveal evolutionally conserved regions within their promoters, we will employ a range of statistical model-based algorithms (Clover [1]) and Glam [2]) to identify statistically over-represented cis-Elements for Dopamine-Regulated Gene expression (CEDRG). We will systematically evaluate the predicted known and novel cis-element binding activity by ChIP-chip analysis and gel shift assay, respectively, in the putative proximal DRG promoters. Specific Aim 3: We will determine functional interactions of CEDRGs by detecting statistically significant CEDRG clusters, and by assaying transcription activity of CEDRG clusters in a striatal cloned cell line (ST14A). Furthermore, we will employ a "safe-haven" transgenic strategy to evaluate in vivo function of identified CEDRG in transgenic mice. Finally, we will examine DRG expression in mice deficient in transcription factors corresponding to the CEDRG to conclusively determine their involvement in DRG expression. The molecular and bioinformatics analyses are integrated throughout the project to overcome major limitations of each individual technique. The information derived from systematic analyses of DRGs will provide critical insights into dopamine functions and identify novel dopamine-regulated transcription factors and thus greatly facilitate the development of novel treatment strategies for dopamine-associated neuropsychiatric disorders such as drug addiction. |
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2009 — 2013 | Chen, Jiang-Fan | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cellular Basis of Motor, Anti-Dyskinesic and Neuroprotective Benefits of A2a Rece @ Boston University Medical Campus DESCRIPTION (provided by applicant): During the last 5 years, the adenosine A2A receptor (A2AR) has emerged as a leading non-dopaminergic therapeutic target in Parkinson's disease (PD). This excitement came primarily from two lines of experimental and clinical investigations showing multiple potential benefits of A2AR antagonists in PD (i.e. confirmed motor stimulation, potential of neuroprotection and possible anti-dyskinesia). However, major knowledge gaps need to be addressed: the molecular mechanisms for the A2AR antagonist monotherapy versus the A2AR antagonist combined therapy with L- DOPA, and for possible anti-dyskinesic as well as neuroprotective effect of A2AR antagonists. Most importantly, are the multiple benefits by A2AR antagonists mediated by a common mechanism or distinct cellular actions? The overall goal of this proposal is to dissect out the cellular basis for the multiple functions of A2AR antagonists (i.e. motor stimulation, possible anti-dyskinesic effect and potential neuroprotection) in animal models of PD. The core hypothesis of the proposal is that the distinct anti-PD properties of A2AR antagonists are mediated by A2ARs in different cellular elements. Specifically, A2AR antagonists act at post-synaptic striatopallidal neurons, presynaptic cortico-striatal glutamatergic terminals and microglia to exert motor stimulant, anti-dyskinesic and neuroprotective effects, respectively. Our three KO models with cell-type specific inactivation of the A2AR in striatal neurons, forebrain neurons, or microglial cells will allow us to investigate this hypothesis. Beyond providing basic neurobiological insights on the integrated function of A2ARs in brain, the dissection of potential distinct cellular mechanisms of A2AR antagonists opens up new and real possibilities of selectively manipulating A2AR's motor, anti-dyskinesic and neuroprotective effects by targeting different cellular elements (striatopallidal, cerebral cortical neurons, and microglia). The results of the proposed research will provide a cellular basis for the better clinical use of A2AR antagonists in PD patients. |
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