Chen Gu, Ph.D. - US grants
Affiliations: | 2000 | University of Colorado Anschutz Medical Campus, Denver, Aurora, CO |
Area:
Neuroscience BiologyWe are testing a new system for linking grants to scientists.
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, Chen Gu is the likely recipient of the following grants.Years | Recipients | Code | Title / Keywords | Matching score |
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2009 — 2013 | Gu, Chen | 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. |
Mechanism and Function of Kv Channel Targeting @ Ohio State University DESCRIPTION (provided by applicant): The long-term objectives are to understand how voltage-gated potassium (Kv) channels are localized into the proper subcellular compartments and how their localization affects neuronal excitability, and thus to develop new strategies for treating neurological diseases. Kv channel dysfunction causes diseases of brain, heart and muscle. Kv channels are the primary targets of pharmaceutical interventions to treat epilepsies, arrhythmias, neuropathic pain, and multiple sclerosis. Due to broad channel expression in many cell types, blockers or activators often bring severe side effects. Recent studies show that each Kv channel displays a distinct pattern of polarized targeting in neurons. It is the emerging theme that such polarized targeting affects neuronal excitability. However, the exact mechanism and function of Kv channel targeting remain mystery. Kv3 (Shaw) channels are unique among Kv channels in their high activation threshold and rapid deactivation kinetics. They are required for rapid spiking and involved in dendritic integration and transmitter release. Human adult-onset ataxia caused by mutations in Kv3.3 gene is a testament for their important functions. Reflecting their diverse functions, Kv3 channels display complex targeting patterns that are governed by unknown mechanisms. Our preliminary studies show that the two splice variants of Kv3.1 have identical channel properties but differentially regulate action potential firing. Interestingly, they differ in axon-dendrite targeting. Based on our preliminary data, we propose a new model that action potential firing is regulated by Kv3 channel targeting, which is in turn regulated by alternative splicing and protein phosphorylation. We will test three hypotheses in this model with three aims. By taking a multidisciplinary approach that includes electrophysiology, imaging, molecular biology and protein biochemistry techniques, we will determine whether: (Aim 1) polarized targeting of Kv channels is critical for action potential firing;(Aim 2) ankyrin G at the axon initial segment functions as a conditional barrier for Kv3 splice variants;(Aim 3) protein phosphorylation regulates Kv3 channel targeting and hence action potential firing. Our research will contribute to generate a new therapeutic strategy and reveal new drug targets for specifically controlling Kv3 channel functions in neurons, e.g. developing small peptides and kinase inhibitors as the treatment of ataxia, epilepsy and sleeping disorders. PUBLIC HEALTH RELEVANCE: Kv channels are the primary targets of pharmaceutical interventions to treat many diseases, in which the specificity of channel modulation is the key. Recent studies show that each Kv channel has its characteristic distribution pattern in nerve cells. Therefore, our project to understand how Kv channels are localized to regulate functions of nerve cells will contribute to generate novel strategies for treating diseases of the nervous systems. |
0.948 |
2016 — 2019 | Gu, Chen | 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. |
Polarized Initiation of Varicosity Formation in Central Neuron Mechanosensation @ Ohio State University PROJECT SUMMARY Little is known about the role of micromechanical stress in regulating neuronal morphological and functional polarity. Diffuse axonal injury caused by mechanical impact displays characteristic axonal varicosities (swelling or beading), which are a prominent feature of traumatic brain injury (TBI). Abundant axonal varicosities are also a key sign for irreversible neurodegeneration in Alzheimer's and Parkinson's diseases, and multiple sclerosis. Under physiological conditions, a lower level of axonal varicosities can be observed in the brain. Although axonal varicosities profoundly affect action potential propagation and synaptic transmission, how they are specifically induced in axons by mechanical stress and regulated in health and disease remains a mystery. Our preliminary studies have led to several novel findings to shed light on this important question. We found that mechanical stress induces varicosity formation in unmyelinated axons, but not in dendrites or myelinated axons of central neurons. This process is unexpectedly rapid and reversible, where a transient receptor potential (TRP) channel acts as the major mechanosensitive (MS) ion channel. We further identified a novel binding protein of this channel, which regulates microtubule (MT) disassembly in response to Ca2+ influx. Moreover, we observed the rapid development of axonal varicosities in the brain of a mouse model of mild TBI. Based on our preliminary results, we propose an original hypothesis that micromechanical stress preferentially induces axonal varicosities in central neurons, and this process is regulated by axonal intrinsic and extrinsic mechanisms. To test this hypothesis, we will use a multidisciplinary approach including novel microbiomechanical assays, protein biochemistry, electrophysiological recording, state-of-the- art imaging, myelin coculture, knockout mice and a mild TBI mouse model. We will determine (Aim 1) whether targeting and activity of MS ion channels regulate polarized mechanosensation in central neurons, (Aim 2) how MT disassembly is induced by intra-axonal Ca2+ increase and in turn leads to varicosity formation, and (Aim 3) whether the pattern of axonal varicosity formation in the mild TBI mouse model is regulated by myelin, the MS channel and its binding protein. This project represents an underexplored research field with many open questions. This research is significant because it will provide novel mechanistic insights into a new form of central neuron polarity, polarized mechanosensation. |
0.948 |
2017 — 2018 | Gu, Chen | R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Regulation of Gray Matter Myelination by Adolescent Binge Ethanol Treatment @ Ohio State University Project Summary Chronic ethanol consumption has adverse effects on higher brain functions. The hippocampus, which plays important roles in learning, memory and anxiety, is known as one of the most sensitive targets for the neurotoxic effects of ethanol. Adolescents binge drink more than any other age group. Adolescents with alcohol use disorders develop deficits in executive functioning, learning and memory, but the pathogenic mechanisms remain poorly understood. Adolescence is a developmental period associated with maturation of cognitive ability, personality, and frontal cortical executive functions. This coincides with gray matter myelination. Gray matter demyelination can be induced by early life stress (e.g. social isolation), and is implicated in a number of conditions, such as Alzheimer's disease, multiple sclerosis, temporal lobe epilepsy, and psychotic disorders. It is known that chronic ethanol consumption correlates with demyelination and cognitive deficits. Based on our preliminary data, we propose to test an original hypothesis that binge-like ethanol exposure in adolescence damages brain function, in part, through gray matter demyelination, and this demyelination can persist into adulthood and be blocked by antioxidant treatment. We will use a well- establish animal model that has been extensively validated in the field, combined with behavioral and morphological studies. We will determine (1) alterations of behavior and gray matter myelination following binge-like ethanol exposure in adolescent and adult mice, and (2) effects of antioxidant treatment on ethanol- induced demyelination. This exploratory project will allow my laboratory to establish in vivo animal models to systematically study the role of gray matter demyelination following adolescent binge ethanol exposure. These studies may identify an effective antioxidative treatment that can protect myelin from the damage induced by adolescent ethanol exposure. |
0.948 |