1986 — 1990 |
Tang, Cha-Min |
K08Activity Code Description: To provide the opportunity for promising medical scientists with demonstrated aptitude to develop into independent investigators, or for faculty members to pursue research aspects of categorical areas applicable to the awarding unit, and aid in filling the academic faculty gap in these shortage areas within health profession's institutions of the country. |
Astrocyte-Glutamate Interaction @ University of Pennsylvania
The long term goals will be to identify non-neoplastic neurologic disorders which may be based on pathologies of astrocyte-neuronal interactions. More specifically the role of astrocytes in the brain edema associated with Reye's syndrome will be studied. A variety of experiments will be proposed to test the hypothesis that "Mammalian astrocytes take up sodium and swell when exposed to levels of glutamate and ammonia found in Reye's syndrome. The mechanism for this sodium influx is an astrocyte specific membrane cotransport process which is involved in the normal clearance of the putative neurotransmitter, glutamate, from the neuronal microenvironment." Secondly, using patch clamping techniques experiments are proposed to address the question "Does the astrocyte depolarization by glutamate represent an electrogenic cotransport of glutamate or does it represent the opening of a glutamate gated ionic channel?" Finally the effect of blocking glutamate and sodium cotransport into astrocyte will be studied. Will the blockade of glutamate sodium cotransport result in decreased astrocyte swelling? Will the accumulation of glutamate in the synaptic space result in abnormal neuronal integration?
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0.951 |
1990 — 1994 |
Tang, Cha-Min |
R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Properties and Roles of Glutamate Channels in the Cns @ Graduate Hospital (Philadelphia)
The post-synaptic receptor-channel complex is the molecular element which mediates the transduction of a chemical signal into an electrical signal. The precise kinetic relationship of this chemical to electrical transduction has been difficult to determine with a temporal resolution that is relevant for synaptic signalling in the mammalian CNS. The development of a novel rapid "concentration-clamp" in preliminary studies now provides the means to address this problem. Preliminary results suggest that the rates of activation, desensitization, and recovery from desensitization of the glutamate channels are far faster than previously thought. Preliminary studies has also revealed a previously unreported high conductance rapidly desensitizing glutamate channel. This channel has characteristics that strongly suggest it may mediate the fast epsc in much of the mammalian CNS. This grant proposal seeks to more firmly establish the relationship between the rapidly desensitizing glutamate channel and the faster epsc. The identification of this new glutamate channel and its fast kinetic characteristics suggest that the kinetic model of synaptic transmission derived from studies at the cholinergic synapse at the neuromuscular junction may not be applicable for the glutamate synapse in the CNS. This grant proposal seeks to examine an alternate model for describing the kinetics of the signal transduction process at the CNS synapse. Other questions to be addresses during the grant award include: What factors may modulate the kinetics of the different glutamate channels? Are there pharmacologic agents that can differentiate between the low conductance and the high conductance quisqualate channel? are the properties of glutamate channels obtained from neurons in brain slices different from those obtained from cultured or enzyme treated neurons?
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0.972 |
1998 — 1999 |
Tang, Cha-Min |
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. |
Method to Probe Postsynaptic Modifications in Plasticity @ University of Maryland Baltimore
DESCRIPTION (Adapted from applicant's abstract): This 'small grant' seeks to develop a method to apply neurotransmitters rapidly and focally in brain slice preparations in such a manner as to activate individual dendritic spines directly. Such a method could be used to distinguish presynaptic from postsynaptic actions in studies of synaptic plasticity, to map the distribution of glutamate receptors, and to study dendritic excitability. We have developed a method for light-induced release of glutamate from caged compounds under tissue culture conditions. This method relies on single-mode optical fibers to achieve saturating concentrations of glutamate within a 3 pm Spot in less than 1 ms. We now seek to apply this methodology to the brain slice preparation.
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0.972 |
1999 — 2002 |
Tang, Cha-Min |
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. |
Synaptic Integration by Hippocampal Neurons @ University of Maryland Baltimore
DESCRIPTION: (Applicant's Abstract) This project seeks a clearer understanding of both the postsynaptic factors that shape fast IPSCs and EPSCs as well as the mechanism by which synaptic inputs are integrated on the dendrites of hippocampal neurons. One set of experiments will determine the impact of GABAA and AMPA receptor desensitization on synaptic transmission. The physiological impact of desensitization has been inferred, in large part, by extrapolation from the results of kinetic studies of receptors in excised outside-out (O-O) membrane patches. The implicit assumption is that the kinetic properties of synaptic receptors can be faithfully modeled by those of receptors in O-O patches. However, this assumption has yet to be directly tested for AMPA and GABAA receptors. Indeed, our preliminary data suggest that the process of patch isolation alters the desensitization properties of both AMPA and GABAA receptors, with the effect on the latter receptors being especially marked. A second set of experiments will determine the mechanism by which synaptic inputs separated in time and space are combined by the dendrite, a fundamental issue in neurobiology that remains poorly understood. Our preliminary data suggest that summation on dendrites cannot be adequately described by a single process similar to that demonstrated in classic studies of the muscle endplate. Instead, we postulate that summation readily switches between different modes (such as linear, sublinear, and supralinear). We propose that such mode switching is a defining feature of temporal and spatial summation by dendrites of neurons in the central nervous system. Hippocampal neurons in dissociated cultures and in organotypic slice cultures will be studied. Postsynaptic responses will be recorded with patch clamp techniques. Glutamate and GABA will be applied to dendritic receptors in situ with the use of a novel method of rapid focal photolysis that we have recently developed. This innovation has enabled us to overcome the major technical problems that had rendered these fundamental issues previously inaccessible.
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0.972 |
2002 — 2004 |
Tang, Cha-Min |
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. |
An Infrared Fiber Optic Based Guidance System For Dbs @ University of Maryland Baltimore
[unreadable] DESCRIPTION (provided by applicant): [unreadable] [unreadable] Deep brain stimulation may be used to treat a number of neurological and psychiatric disorders. For treatment in patients with Parkinsons' disease it is necessary to place the electrode precisely within the center of the target nucleus. Precise electrode placement provides optimal therapeutic results while minimizing possible side effects. Currently, the final coordinates for the electrode is determined by electrophysiological mapping. It is a slow, painstaking process not without potential complications. We propose to develop and evaluate two procedures to compliment current microelectrode mapping procedure. A fiberoptic-based probe will be employed to optically map the boundaries of the STN and GPi using only a single electrode tract. We also propose to develop a method to detect blood vessel using fiber sensors as part of the microelectrode assembly. [unreadable] [unreadable] Besides a role in the treatment of Parkinson's disease, the methods to be developed may be applied to stereotactic brain procedures for other neurological and psychiatric disorders. For example, it could be used to more precisely guide the biopsy of deep seated brain lesions. It could be used to more safely guide the placement of depth electrode for the diagnosis and treatment of refractory seizures. And optically guided stimulating electrodes may someday be used to treat depression and other psychological disorders.
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0.972 |
2004 — 2007 |
Tang, Cha-Min |
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. |
Oct-Guided Interventions For Pain Management @ University of Maryland Baltimore
[unreadable] DESCRIPTION (provided by applicant): [unreadable] The spinal epidural space is a poorly accessible site within the bony spinal canal where therapeutic interventions that affect millions of Americans are carried out each year. Examples include epidural anesthesia and management of low back pain. Between two and three million epidurals are performed each year in this country for obstetrical analgesia. A comparable number of epidural anesthesia procedures are performed as part of other surgical indications. Low back pain has been estimated to exact >$50 billion a year burden on the American economy. The pathology typically lies within or immediately adjacent to the epidural space. Existing clinical imaging technology is unable to provide the spatial resolution or the realtime capabilities needed for therapeutic interventions within this space. There is a great unfilled need to be able to clearly image in real-time structures such as individual nerve roots, blood vessels, dura, free disc fragments, and fibrous scar tissue within and adjacent to the spinal epidural space. Optical coherence tomography (OCT) is an emerging technology that is ideally and uniquely suited for imaging within the spinal canal. The first goal of this project is to modifiy and adapt catheter-based OCT technology for applications in the spine. The second goal is to determine the feasibility and advantages of OCT-guided interventions for acute and chronic pain management. This will be a collaborative effort between an academic medical center and the industry leader in catheter-based OCT technology. [unreadable] [unreadable]
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0.972 |
2019 |
Tang, Cha-Mei Tang, Cha-Min |
R41Activity Code Description: To support cooperative R&D projects between small business concerns and research institutions, limited in time and amount, to establish the technical merit and feasibility of ideas that have potential for commercialization. Awards are made to small business concerns only. |
Coherence Gated Doppler For Dentistry
Abstract If there were a simple and accurate means to ?take the pulse? of a tooth, (i.e. functionally similar to a pulse oximeter that could be clipped on a tooth rather than the tip of a finger) the quality and cost of dental care would be significantly improved. The ability to measure dental pulp blood flow provides the most direct means to determine the viability of a tooth and is a vital piece of information required for nearly all dental management decisions. It is an unmet need identified in NIDCD?s PA-15-336. Conventional blood flow detection approaches are precluded by the rigid structure of teeth and the invariant volume of vascular space within the root of the tooth. To circumvent the latter constraint we combined principles from two separate modern optical technologies (laser Doppler and coherence gated tomography) to create a hybrid technology with unique capabilities, ?coherence gated Doppler? (CGD) (US Patent 9,486,140). But the challenge for dentists is not just the certainty of information on whether a tooth is viable or not, but in the prompt access to that information. The dentist can wait until the signs of death becomes clear before making a therapeutic decision. But the delayed action can have significant negative consequences for preserving function. Examples include bone resorption caused by chronic infection requiring expensive and time-consuming bone grafts if the tooth is to be replaced by an implant, greater instability if that tooth is to be left in place after receiving endodontic therapy, and unnecessary pain, cost, and time for repeat office visits by the patient. Current standard of practice has evolved to a suboptimal compromise between diagnostic certainty and promptness of intervention. If high diagnostic accuracy can be provided painlessly, at low cost within minutes by the dental assistant, it will have a profound impact on dentistry. The broad goal of this STTR application is to demonstrate the feasibility of ?transmission mode? CGD as such a technology. Specifically, this phase I project will determine whether CGD has the sensitivity and specificity to detect blood flow within the root of a tooth while rejecting any flow signal from outside the tooth. This proof of concept demonstration will be carried out in freshly extracted teeth and in a ferret canine teeth animal model. Furthermore, the performance of CGD will be compared against the predicate laser Doppler flowmetry technology.
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0.901 |