|PI||Type||Grant #||Title||Start date||End date||Funding status||Abstracts/Aims|
|Chesnut||R01||1R01NS080648-01||Managing severe TBI without ICP monitoring - guidelines development and testing||9/30/2012||7/31/2017||Year 4||The objective of this project is to create guidelines for the treatment of severe TBI in the absence of ICP monitoring and test them. We propose to derive these guidelines by working with a team of clinicians that practice in austere environments in low-to-middle income countries (LMICs) and routinely make decisions based either on a treatment protocol, their clinical experience, or both.|
|Chesnut/Temkin||TRACK||1U01NS086090-01 (Manley, PI)||Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI)||9/30/2012||8/31/2018|| ||TRACK-TBI will create a large, high quality database that integrates clinical, imaging, proteomic, genomic, and outcome biomarkers to establish more precise methods for TBI diagnosis and prognosis, refine outcome assessment, and compare the effectiveness and costs of TBI care.|
|D'Ambrosio||R21||NS085459||NOVEL INFLAMMATORY TARGETS TO PREVENT POSTTRAUMATIC EPILEPTOGENESIS||5/1/2014||4/30/2016||year 2||Inflammation is a consistent feature of both the injured brain and of the epileptic brain, and mounting evidence indicates a role for inflammation in acquired epileptogenesis. The rational development of anti-inflammatory prophylaxes for PTE requires the understanding of the diverse components of inflammation that are necessary for posttraumatic epileptogenesis. Our proposed studies will use a realistic model of posttraumatic epileptogenesis, and an effective treatment that prevents it, to dissect out the inflammatory mediators involved in epileptogenesis after head injury.|
|Ellenbogen||R25||NS095377-01 NINDS 2015-2020||Summer Research Experience in Translational Neuroscience and Neurological Surgery||1/1/2016||12/31/2020|| ||The primary goal is to immerse a selected group of high school and university students in a translational environment of basic neuroscience, neural engineering and neurological surgery.|
|Kim||R01||5R01NS088072-02||Predicting cerebral aneurysm recurrence using Doppler guidewire measurements||9/1/2014||5/31/2019|| ||The proposed study will use dual-sensor Doppler guidewire technology to measure blood flow velocity and blood pressure from within cerebral blood vessels harboring intracranial aneurysms during treatment, and apply these measurements to determine causes of treatment success and failure. The results of this study could be used by physicians to alert them to aneurysms at risk for treatment failure, and allow them to provide either additional treatment or more frequent follow-up to prevent aneurysm regrowth and life-threatening brain hemorrhage.|
|Mac Donald||DoD||PT120517-25||Chronic Effects of Neurotrauma Consortium/ Assessment of Long-term outcome and Disability in Active-Duty military Prospectively examined following concussive blast TBI (ADAPT)||10/1/2014||9/30/2016|| ||Evaluate long-term impact of concussive blast TBI on US military service members|
|Mac Donald||NIH||1R01NS091618-01||EVALUATION OF LONGITUDINAL OUTCOMES IN MILD TBI ACTIVE-DUTY MILITARY AND VETERANS (EVOLVE)||1/1/2015||3/31/2020|| ||The overall goal is to investigate long-term advanced MR imaging measures and clinical outcome of concussive traumatic brain injury (TBI) sustained during deployment in US military personnel. We will relate these findings to prospectively acquired longitudinal imaging and clinical data from the acute/sub-acute, and early chronic stages following concussion collected on these patients as part of previous collaborative efforts. We hypothesize that early clinical and imaging measures can be used to predict 5-7 year late stage clinical outcome which will offer important insight into the long term impact of war-time mild TBI thereby guiding new recommendations for clinical management and therapeutic intervention.|
|Mikheev||R21||5R21NS082542-02||Generation of TWIST1 reporters through characterization of TWIST1 dependent network||9/1/2013||8/31/2016||no-cost extension||We recently found that stable inhibition of TWIST1 expression in primary glioma stem cells (GSCs) isolated from patients dramatically reduced stem cell activity and tumorigenicity. We propose now to generate TWIST1 reporters suitable for application in High-throughput screening for TWIST1 inhibitors targeting specifically cancer stem cell activity. We will use an innovative approach that combines microarrays profiling of our human primary GSCs with and without TWIST1 inhibition, CHIP-sequencing and interrogation of transcriptional factor network using bioinformatics tools followed by reporters construction and validation.|
|Morrison||R21||5R21NS084217-02||A transgenic model to study Bif-1 mediated neuroprotection in injury and disease||3/15/2014||2/29/2016|| ||Utilizing a novel mouse model we hope to develop, we will assess whether an uncharacterized mitochondrial protein that is neuroprotective in cultured neurons against amyloid toxicity confers protection against stroke and damage associated with a mouse model of Alzheimer's disease when overexpressed in neurons. |
|Morrison||Bright Focus Fnd||A2014237S||Bif-1 therapy for cognitive impairment and neuropathology in AD||7/1/2014||6/30/2017|| ||The major goal of this project is to create a transgenic mouse line that expresses the neuron-specific form of Bax-interacting factor-1 (Bif-1) in a neuron-specific and inducible manner to test the hypothesis that maintenance of Bif-1 expression in neurons can reduce cognitive impairment and neuropathological changes in a mouse model of Alzheimer’s disease. |
|Mourad||DoD|| ||Localizing and assessing amputee pain with intense focused ultrasound||9/15/2015||9/14/2018|| ||Human subject studies assessing the ability of intense focused ultrasound (iFU) under ultrasound image guidance to assess the sensitivity of tissue within residual limbs, including neuromas and targeted muscle reinnervation (TMR) sites.|
|Mourad||FUSF|| ||Modulated focused ultrasound for treatment of demylenating axons in multiple sclerosis lesions: pilot animal studies||6/1/2015||11/30/2016|| ||Initial tests of the potential for ultrasound to activate neurons within model multiple sclerosis lesions in a manner that ameliorates the structure of those lesions.|
|Ojemann||R01||R01NS065186||Electrocorticography signals for human hand prosthetics||5/1/2010||4/30/2015||no-cost extension||Uses linear and nonlinear measures of motor function, with feedback, to control a prosthetic hand.|
|Ojemann||R25||R25NS079200||Neurosurgery research training in interdisciplinary neuroscience||4/1/2012||3/31/2017|| ||
The University of Washington has a long and strong tradition of training residents in neurological surgery for careers in academic medicine. This proposal will support the research component of this training by placing the resident in an interdisciplinary research environment, preparing the candidate for neurosurgically-inspired science projects and a future career as an interdisciplinary investigator in funded projects. Future candidates will pursue topics in one of three core strengths of ongoing department work – Neural Engineering, Neuro Oncology, and Restorative Medicine. The first candidate will pursue research in brain-computer interface in a structured laboratory environment that studies, in ongoing collaborative projects between basic neuroscientists, neural engineers, and neurosurgeons, control and device considerations in brain-computer interface. The 12 month experience will include both independent
investigation but in the context of a mature project to ensure success. Combined with a didactic program that is supported by the department and superior clinical experience, the resident will be prepared to enter into collaborative neural engineering projects at the conclusion of the support period.
|Ojemann||NSF|| ||Collaborative Research: US-German; Optimization of human cortical stimulation||7/1/2015||6/30/2018||year 1 of 3||Animal models of cortical stimulation will be developed to maximize stimulation of regions of interest. 2. These models will be validated across a variety of inter-electrode distances and geometries (based on the model results) in sheep studies. 3. Conventional human cortical stimulation will be modeled with varying spatial patterns of stimulation proposed and 4. These models will be validated with surface stimulation and recording in patients with implanted electrodes.|
Human brain tissue collection and preservation for cortical neuronal cell type classification.
The research project described in this plan is critically important to achieving an Allen Institute goal to characterize the functional architecture of the human neocortex at the level of cell types and local circuits and create a publicly available scientific resource of this information to advance the understanding of the brain. Such characterization includes molecular, anatomical and physiological analysis at the single cell level, using tissues from human brain.|
More specifically, characterization is expected to include:
- Transcriptional analysis (e.g., PCR, RNA sequencing).
- Filling of single neurons with dyes (e.g., biocytin, Lucifer yellow) for morphological reconstruction and quantitative anatomy.
- In vitro slice electrophysiology for physiological characterization and correlated analysis of functional, morphological and molecular properties of individual cells, and for studies of population dynamics using calcium-sensitive dyes.
- Analysis of the molecular composition of synapses (e.g., array tomography).
- Extended maintenance of cortical tissues in culture for virally-mediated molecular genetic studies of circuit function.
In this collaboration, the expertise and resources of University of Washington will be applied in the areas of consenting, scheduling, arrangement of tissue collection, provision of facilities for minimal tissue processing, and management of IRB approvals, to provide human brain tissue and de-identified patient information to the Allen Institute.
Investigators from both parties will work together to establish appropriate exclusionary criteria, determine scientifically useful patient information that can be shared with the Allen Institute, establish requirements for minimal Institute use of UW Neurosurgery facilities for tissue processing, and establish logistical and administrative processes that enable rapid communication, transfer and processing of tissue to meet tissue viability needs for robust characterization of neuronal cell types.
The parties anticipate that the collaboration will result in profiling of tissues on a regular basis throughout the year, up to once a week.
|Temkin||DoD||W81XWH-14-2-0176 (PI: Temkin) ||Traumatic Brain Injury Endpoints Development (TED)||9/20/2014||9/29/2019|| ||The goals are to harmonize and curate data from military, civilian and sports-related TBI studies to create the TED Metadataset in order to identify endpoints to validate as measures for diagnostic and therapeutic trials for TBI. Existing research networks will be leveraged to validate endpoints and once validated will be submitted for the FDA qualification process for Drug Development Tools for TBI trials.|
|Mourad||NSF|| ||Bothell summer students|| || || ||
|Williams||NASA||NNX16AE78G||Zero G and ICP: Invasive and noninvasive ICP Monitoring of Astronauts on the ISS||2/5/2016
||10/4/2022||"This research will systematically apply established clinical and investigational diagnostic methods for disorders of cerebrospinal fluid (CSF) circulation to a cohort of astronauts at risk for Visual Impairment Intracranial Pressure (VIIP). This research will result in the first-ever invasive measurements of intracranial pressure (ICP) in astronauts before, during, and after an ISS mission, providing the first physiologic evidence to demonstrate if VIIP is associated with alterations of ICP in long duration spaceflight.
1) To determine whether ICP in space is elevated in comparison to baseline ICP on Earth, and whether ICP after return to Earth differs from baseline values by measuring ICP in astronauts before, during, and after an ISS mission by invasive methods.
2) To validate noninvasive ICP measurement methods and their correlation with invasive ICP before, during, and after spaceflight, and to quantify their error of measurement.
3) To determine the correlation of ICP changes to other indicators of VIIP by collecting biomarkers of VIIP for correlation to ICP."
|Hevner @ SCH||R01||5R01NS085081-03||INTERMEDIATE NEURONAL PROGENITORS IN NEOCORTICAL DEVELOPMEN||9/1/2013||5/31/2018|| || Developmental disorders of the cerebral cortex include autism, epilepsy, and intellectual disability. This project investigates basic mechanisms of cerebral cortex development, focusing on the role of intermediate neurogenic progenitors, a recently discovered progenitor type that appears to be critical in the development of cortical layers, areas, and connections.|
|Hevner @ SCH||R01||1R01NS092339-01A1||DEVELOPMENT AND MALFORMATIONS OF THE DENTATE GYRUS||3/1/2016||12/31/2020|| || The dentate gyrus (DG) is a region of cerebral cortex in the medial temporal lobe that is frequently involved in epilepsy and other neurodevelopmental disorders. Interestingly, DG neurogenesis is extremely prolonged relative to other cortical areas, and depends on migrations of progenitor cells within the dentate migration stream (DMS) and other transient neurogenic niches. Previous studies from the PI's lab have shown that one type of cortical progenitor cells, known as intermediate progenitors (IPs) or transit-amplifying cells, specifically express Tbr2, a T-box transcription factor, during DG development as well as adult neurogenesis. New preliminary data show that Tbr2+ IPs plays major roles in transient neurogenic niches and dentate migration streams that are essential to morphogenesis of the dentate gyrus. For example, Tbr2+ IPs appear to pioneer the DMS and enhance the subsequent migration of neural stem cell (NSC)-like radial glial progenitors (RGPs). Aims 1 and 2 of this project will analyze transient DG niches and cell migrations in mice, and determine the roles of RGPs and IPs in gyrogenesis (development of convoluted cortex). Aim 3 extends these approaches to characterize DG malformations in mutant mice with defects of IP or radial glial progenitor (RGP) differentiation. |
|Ramirez @ SCH||R01||5R01HL126523-02||UNRAVELING RESPIRATORY RHYTHM GENERATION IN THE MEDULLARY NETWORK||1/1/2015||11/30/2018|| ||Breathing is generated by a neuronal network that is distributed along the rostro-caudal axis of the ventrolateral medulla ('ventral respiratory column', VRC). This network gives rise to three distinct phases: inspiration (I), post-inspiration (Post-I), and active expiration (AE). Many disorders are associated with disturbances in different forms of breathing and the response to hypoxia. Thus understanding how these phases of breathing are generated and dynamically regulated under various conditions such as hypoxia is of great basic scientific and clinical interest. In this project we introduce two novel rhythmicall active brainstem slice preparations that allow us to study the integration of synaptic, intrinsic and modulatory properties in the wider medullary network to an extent that was not possible before. Based on our preliminary data we propose the hypothesis that post-I and inspiration are generated by an excitatory column that extends rostrally from the pre-Bötzinger complex into the Bötzinger complex. This distributed excitatory network interacts with GABAergic and glycinergic mechanisms as well as intrinsic membrane properties that will be explored in the horizontal slice preparation using a variety of electrophysiological, pharmacological, and optogenetic approaches (Aim 1). Insights gained in this horizontal slice preparation will be compared with data obtained from two transverse slice preparations that isolate the caudal and rostral portion of this excitatory column (Aim 2). This approach will allow us to differentiate rhythmogenic mechanisms occurring at the caudal and rostral end of this column. Concepts revealed in these in vitro findings will then be tested in a spontaneously breathing in vivo preparation (Aim 3). We expect that the introduction of these novel in vitro preparations, combined with modern optogenetic techniques and a rigorous integration with in vivo approaches will allow us to revisit existing models of respiratory rhythm generation. This may lead to a better understanding of various issues that remain unresolved and unexplained at the current state of knowledge in the field of neural control of breathing.|
|Ramirez @ SCH||R01||HA126523||Unraveling respiratory rhythm generation in the medullary network||1/1/2015||11/20/2018|| ||Many neurological disorders are associated with breathing disorders that affect the control of inspiration and various forms of expiration. We identify the cellular mechanisms in a neuronal network that is located within the lower brainstem and that controls the different phases of breathing.|
|Browd @ SCH|| ||Baylor-PCORI SubContract||A Randomized Controlled Trial of Anterior Versus Posterior Entry Site for CSF Shunt Insertion||1/1/2015||12/31/2018|| || |