MIT/WHITEHEAD/BROAD COMPUTATIONAL GENETICS TRAINING PROGRAM
K David, Professor
Massachusetts Institute Of Technologycity: Cambridge country: United States (us)
Grant 5T32HG004947-03 from National Human Genome Research Institute
Abstract: We propose to establish a new interdisciplinary research training program in Computational Genetics as a collaborative effort between MIT, the Whitehead Institute, and the Broad Institute of MIT and Harvard. The goal of this program is to train MIT students to be effective interdisciplinary scientists, working as team members with biologists to develop new algorithms, tools, and approaches for analyzing genomic and genetic data and expressing this analysis in the form of principled predictive models. The program faculty will consist of five MIT EECS and Mathematics faculty, four Whitehead faculty members, and four members of the Broad Institute of MIT and Harvard. The major research disciplines of this program include 1) the development of new approaches and algorithms for the analysis of data from genomics and genetics based experiments and studies; 2) approaches for the principled design of studies based upon past data; 3) the construction of computational models that explain complex phenotypes and biological phenomenon; 4) and the development of approaches for interpreting genomic, genetic, and clinical data relevant to human health and disease. It is proposed that four pre-doctoral trainees be supported in this program, each for a period of two years (a total of 8 slots). We have been running a training program in this area for over seven years, and our students to date have made substantial contributions to the field. Among our recent graduates are faculty at Stanford, Berkeley, Univ. of Washington, Princeton, Duke, and CMU. Our pool of applicants is unusually strong, with 592 applicants in 2008 in relevant sub-areas of Computer Science. Trainees in our proposed research training program will have a very rigorous technical and quantitative foundation from the MIT graduate program in Computer Science, combined formal interdisciplinary course work and a co mentorship arrangement between a Computer Science and a Biology faculty member. The strong technical skills present in our pre doctoral students have provided an excellent foundation for the creation of ground breaking new approaches and algorithms in Computational Genetics. PUBLIC HEALTH REVELANCE - We will train scientists who can discover links between genetic information and risks for human disease. These studies can suggest appropriate therapies for certain diseases and give clues towards the development of new therapeutics. As more data form Genome Wide Association Studies becomes available, we expect that genetic information will become an important component of preventative medicine
Keywords: Genetic; Training Programs
Project start date: 2009-07-08
Project end date: 2014-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
PFA/PA: PA-06-468
5T32HG004947-03 (2011): $172864
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to K David
MOBILE SEARCH FOR THE VISUALLY IMPAIRED
K David
Iq Engines, Inc.city: Davis country: United States (us)
Grant 2R44EY019790-02 from National Eye Institute
Abstract: The technology developed as part of this NIH SBIR project will transform the cell phone camera of visually impaired individuals into a powerful tool capable of identifying the objects they encounter, track the items they own, or navigate complex new environments. Broad access to low-cost visual intelligence technologies developed in this project will improve the independence and capabilities of the visually impaired. There has been tremendous technological progress in computer vision and in the computational power and network bandwidth of and Smartphone platforms. The synergy of these advances stands to revolutionize the way people find information and interact with the physical world. However, these technologies are not yet fully in the hands of the visually impaired, arguably the population that could benefit the most from these developments. Part of the barrier to progress in this area has been that computer vision can accurately handle only a small fraction of the typical images coming from a cell phone camera. To cope with these limitations and make any-image recognition possible, IQ Engines will develop a hybrid system that uses both computer vision and crowdsourcing if the computer algorithms are not able to understand an image, then the image is sent to a unique crowdsourcing network of people for image analysis. The proposed research includes specific aims to both develop advanced computer vision algorithms for object recognition and advanced crowdsourced networks optimized to the needs of the visually impaired community. This approach combines the speed and accuracy of computer vision with the robustness and understanding of human vision, ultimately providing the user fast and accurate information about the content of any image. The image recognition technology developed in this application will enable the visually impaired to access visual information using a mobile phone camera, a device most people already have. Transforming the camera into an intelligent visual sensor will lower the cost of assistance and improve the quality of life of the visually impaired community through increased independence and capabilities
Keywords: Address; Algorithms; Area; base; blind; Car Phone; cell transformation; Cellular Phone; Classification; Client; Clip; Communities; Complex; Computational algorithm; Computer Vision Systems; coping; cost; Crowding; Data; Databases; Detection; Development; Devices; Ensure; Environment; Family; Feedback; Friends; Glosso-Sterandryl; Human; Hybrid Computers; Hybrids; Image; Image Analysis; improved; Individual; innovation; Intelligence; Label; Learning; Location; Modeling; Monitor; novel; object recognition; open source; Phase; Population; Preparation; Process; Quality of life; Research; Running; Scanning; sensor; Services; Small Business Innovation Research Grant; Social Network; Source; Speed (motion); System; Technology; Telephone; Time; tool; United States National Institutes of Health; Vision; Visual; Visual impairment; visual information; visual search; volunteer
Relevance: The image recognition technology developed in this application will enable the visually impaired to access visual information using a mobile phone camera, a device most people already have. Transforming the camera into an intelligent visual sensor will lower the cost of assistance and improve the quality of life of the visually impaired community through increased independence and capabilities
Project start date: 2009-07-01
Project end date: 2013-11-30
Budget start date: 1-DEC-2011
Budget end date: 30-NOV-2012
2R44EY019790-02 (2012): $499358
DEVELOPMENTAL AND NEONATAL BIOLOGY TRAINING PROGRAM
K David, Sr Assoc. Dean Faculty Affairs
Stanford Universitycity: Stanford country: United States (us)
Grant 5T32HD007249-28 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: The mission of the Training Program in Developmental & Neonatal Biology is subsumed by the overall mission of the NICHD and is focused to ensure that Stanford supplies a diverse pool of highly-trained scientists in research areas, which address the Nation´s biomedical, behavioral and clinical research needs related to the fetus and newborn. Thus, the prime objective of the Program is the education and training of basic and clinical investigators from diverse backgrounds for academic careers in the developmental sciences and neonatology. The Program offers intensive clinical experiences with newborns, the opportunity for clinical investigation, and advanced study in laboratory-based investigation, at the molecular and cellular level in most of the life-science disciplines, including Biochemistry, Chemical and Systems Biology, Developmental Biology, Genetics, Microbiology and Immunology, Molecular and Cellular Physiology, Neurobiology, and Obstetrics and Gynecology. Cross-fertilization of ideas are encouraged that will enrich the research of the basic and the clinically-oriented scientists. For basic science trainees, the Program offers exposure to clinical problems that stimulate their curiosity in human development and enhance the translation from bench to bedside. All trainees have unique opportunities to learn about, as well as contribute to, cutting-edge basic research in productive laboratories with established researchers. They learn about the teamwork required for translational research and can also experience the complexity of large-scale applied clinical research in the intensive care nurseries, supervised by experienced clinical investigators/practitioners. The Program has 4 predoctoral trainees who train for 3 to 4 yrs and receive their PhD degrees; 2 recently graduated postdoctoral trainees train for 1 yr; and 2 post-General Pediatrics residency trainees who possess the knowledge and skills of a Board-Certified general pediatrician train for 2 to 3 yrs. An evaluation process has been developed to obtain each trainee´s feedback in order to make improvements to the program for future trainees. After training completion, academic progress of each trainee is followed annually to assess the success of the Program. An External Advisory Committee offers independent perspectives on the Program´s operation. Because the trainees gain an understanding of priorities in public health, they are poised to make significant research contributions, to ensure that children will be born healthy and wanted, have the full potential for a healthy and productive life, free from disease or disability, and to ensure the health, productivity, independence, and wellbeing of all people through optimal rehabilitation. The clinical and research efforts of trainees from diverse backgrounds will help alleviate the health disparity among segments of the population
Keywords: Biology; Development; Neonatal; Training Programs
Project start date: 1982-09-30
Project end date: 2014-04-30
Budget start date: 1-MAY-2011
Budget end date: 30-APR-2012
PFA/PA: PA-06-468
5T32HD007249-28 (2011): $233771
FUNCTIONAL ANALYSIS OF REPLICATION STRESS RESPONSE PROTEINS
K David, Assistant Professor
Vanderbilt Universitycity: Nashville country: United States (us)
Grant 5R01CA136933-03 from National Cancer Institute
Abstract: The long-term goal of the proposed research is to understand how DNA replication is regulated such that a precise copy of the genome is made. Accurate replication of the genome and continuous surveillance of its integrity are essential for cell survival and the avoidance of diseases such as cancer and premature aging. The genome is constantly exposed to environmental and endogenous genotoxic insults that challenge DNA replication. The replication stress response (RSR) is a subset of the DNA damage response (DDR) that acts during every cell division cycle to deal with these challenges and promote the faithful duplication of the genome. One component of the replication stress response pathway is the checkpoint kinase ATR. ATR promotes faithful DNA replication by regulating origin firing and cell cycle progression, stabilizing stalled replication forks, and promoting the repair and recovery of stalled forks. The mechanisms mediating many of these ATR-regulated activities are poorly understood. We have completed a series of genetic and biochemical screens to define the mechanisms by which the replication stress response regulates DNA replication and maintains genetic stability. These screens included two-hybrid and mass-spectrometry screens to identify proteins that interact with the ATR-ATRIP complex and the TopBP1 regulator of ATR; RNAi screens to define genes that are important for cells to recover from replication fork stress; and RNAi and cDNA overexpression screens to identify genes that when deregulated cause genetic instability. By focusing on proteins identified in more than one of these biochemical and genetic screens and using published genomic/proteomic information, we identified thirty-six high confidence RSR proteins. These include twenty-four candidate RSR proteins not previously linked to replication stress responses. We hypothesize that these novel RSR proteins have distinct functions in replication and DNA damage responses. This hypothesis will be tested using a combination of genetic and biochemical approaches. Completion of this research proposal will define the genome maintenance activities of novel replication stress response proteins and improve our understanding of how a precise copy of the genome is made during every cell division cycle. Accurate replication of the genome and continuous surveillance of its integrity are essential for cell survival and the avoidance of diseases such as cancer and premature aging. The genome is constantly exposed to environmental and endogenous genotoxic insults that challenge DNA replication. This research proposal aims to define the genome maintenance functions of novel replication stress response proteins
Keywords: Actins; base; Biochemical; Biochemical Genetics; biological adaptation to stress; Biological Process; CDK2 gene; Cell Cycle; Cell Cycle Progression; Cell Survival; Cells; CHES1 gene; Chromatin; chromatin remodeling; Chromatin Structure; Complementary DNA; Complex; Data; Defect; Disease; DNA biosynthesis; DNA Damage; DNA Replication Damage; DNA-dependent ATPase; Dysplasia; Family; Foundations; Genes; Genetic; genetic analysis; Genetic Screening; Genome; Genome Stability; Genomic Instability; Genomics; Goals; helicase; human WRN protein; improved; insight; Link; Maintenance; Malignant Neoplasms; Mass Spectrum Analysis; Mediating; Methodology; Mutate; Mutation; novel; overexpression; Pathway interactions; Phosphotransferases; Predisposition; Premature aging syndrome; prevent; protein function; protein protein interaction; Proteins; Proteomics; public health relevance; Publishing; Recovery; Regulation; repaired; Research; Research Proposals; response; RNA Interference; Series; Signal Pathway; Signal Transduction; Stress; System; Testing; TREX1 gene; yeast two hybrid system
Relevance: /Relevance Accurate replication of the genome and continuous surveillance of its integrity are essential for cell survival and the avoidance of diseases such as cancer and premature aging. The genome is constantly exposed to environmental and endogenous genotoxic insults that challenge DNA replication. This research proposal aims to define the genome maintenance functions of novel replication stress response proteins
Project start date: 2009-09-21
Project end date: 2014-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
PFA/PA: PA-07-070
5R01CA136933-03 (2011): $311976
5R01CA136933-02 (2010): $321625
1R01CA136933-01A1 (2009): $321625
K David
Johns Hopkins Universitycity: Baltimore country: United States (us)
Abstract: The goal of this Core is to provide faculty in the Center for Hearing and Balance, and associated laboratories, with access to histological equipment and expertise and assistance. The visualization and quantification of structural features that correlate with physiological, developmental, and/or plastic phenomena within the peripheral and central nervous systems provide fundamental data necessary to infer basic mechanisms of neural function. But with the increasingly specialized nature of science, the expense and difficulty of such studies can place them out of reach for most laboratories. Common resources foster collaborations between scientists with different skill sets and can be the key to implementing exciting research projects that bridge different levels of analysis. Anatomical data frequently support this bridge. The Histology Core will continue to provide assistance as well as access to, and instruction in the tools and resources required for tissue preparation and sectioning for light microscopy. This includes both plasticembedded and frozen sections. The Core provides and maintains a light/fluorescence compound microscope with digital camera for image acquisition and auxiliary workstations for analysis. In addition the Core will enable ultrastructural studies through the services of an experienced electron microsopist
Keywords: Behavioral; Collaborations; Computer software; cost effective; Data; Data Collection; Development; digital; Digital Photography; Educational process of instructing; Electron Microscope; Electron Microscopy; Electrons; Equilibrium; Equipment; experience; Faculty; Fluorescence; Fostering; Foundations; Frozen Sections; Goals; graduate student; Hearing; Histologic; Histology; Image; Imagery; immunocytochemistry; implementation research; Individual; Instruction; Investigation; Laboratories; Light; light microscopy; meetings; meter; Methods; Microanatomy; Microscope; Microtome - medical device; Mission; Molecular; Nature; Neuraxis; Neurobiology; Neurophysiology - biologic function; Neurosciences; new technology; Peripheral; Physiological; Plastics; Postdoctoral Fellow; Preparation; Procedures; Process; Research; Research Personnel; Research Project Grants; Research Technics; Resource Sharing; Resources; sample fixation; Science; Scientist; Sensory; Services; skills; Smell Perception; Staging; Staining method; Stains; Structure; Techniques; Time; tissue preparation; tissue processing; Tissues; tool; Training
Budget start date: 1-SEP-2011
Budget end date: 31-AUG-2012
5P30DC005211-10_9002 (2011): $300771
K David
University Of Iowacity: Iowa City country: United States (us)
Abstract: The goal of the Pathology Core is to provide service, expertise and professional consultation to all Investigators of the Cystic Fibrosis PPG. To facilitate these goals the Pathology Core will provide 1) technical assistance for labor intensive histotechnology techniques from tissue processing to specialized staining, 2) professional veterinary pathology support for gross, microscopic and anatomic phenotyping of the CFTR-/-pig model, 3) economic benefits through centralization of equipment, experienced staff and availability of specialized reagents, and 4) consultation and instruction in specialized morphologic techniques and image analysis. Program Investigators will have full access to the Core´s expertise and resources. The Pathology Core will provide its services to Program Investigators in a timely and efficient manner for optimal assessment of tissues. The Specific Aims of the Pathology Core are 1) Provide scientific support, expertise and technical labor for microscopic slide processing from tissues, routine to specialized application of tinctorial stains, and immunohistochemistry techniques. 2) Provide expertise and resources to develop new morphologic or morphmetric techniques as required to facilitate the needs of Project Investigators. 3) Provide veterinary pathology support (though boarded veterinary pathologists) for examination and interpretation of gross to microscopic tissues from the CFTR-/- pig and for consultation in experimental design. 4) Provide expertise and a uniform framework for the standardized assessment of tissues collected by Project Investigators to define a comprehensive anatomic phenotype of the novel porcine CFTR-/- model
Keywords: Anatomy; Comparative Pathology; Complex; Consultations; Cystic Fibrosis; cystic fibrosis mouse; Cystic Fibrosis Transmembrane Conductance Regulator; Disease; Economics; Equipment; experience; Experimental Designs; Family suidae; Functional disorder; Goals; Housing; Human; Human Resources; Image Analysis; Immunohistochemistry; Infectious Agent; Instruction; Laboratories; Lesion; Microscopic; Modeling; Morphology; novel; Pathogenesis; Pathologist; Pathology; Phenotype; Physiology; Play; programs; Reagent; Research Infrastructure; Research Personnel; Resources; response; Role; Services; Slide; Staining method; Stains; Technical Expertise; Techniques; Time; tissue processing; Tissues; Veterinary Pathology
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
5P01HL091842-04_9002 (2011): $89999
MOLECULAR HIERARCHIES IN SALIVARY ADAPTIVE RESPONSES
K David
City Of Hope/beckman Research Institutecity: Duarte country: United States (us)
Grant 5R01DE014183-10 from National Institute Of Dental & Craniofacial Research
Abstract: Saliva is critical for the maintenance of oral function and health. Patients with radiation for head and neck cancer and with Sjogren´s syndrome suffer irreversible damage to salivary glands, rendering them atrophic. The long-term goal of this project is to elucidate the cellular and molecular mechanisms, in particular protein modifications, involved in salivary adaptive responses. Protein modifications by the ubiquitin homologue, SUMO, and phosphorylation have been identified as important regulatory mechanisms governing transcription, DMA repair, cell cycle progression, and intracellular trafficking. This application will focus on the crosstalk and individual roles of SUMOylation-dependent and protein kinase C5 (PKC8)-mediated signaling network in conveying resistance and sensitivity, respectively, towards hypoxia-induced injury in salivary cells. Cellular hypoxia is a stress with important implications in the developmental biology, normal physiology, and many pathological conditions, including a myriad of acute and chronic disease states and cancers. Emerging evidence suggests that hypoxia regulates biological and biochemical functions in many different cell types, yet, the mechanisms by which salivary cells utilize to counteract or reinforce hypoxia-induced cell/DMA damage and growth inhibition are still not clear. We recently demonstrated that hypoxia leads to an increase in SUMOylation in salivary Pa-4 cells, which results in an enhanced NF-tcB-mediated transactivation and an attenuation of PKC8/caspase-3 activation, suggesting that SUMO-dependent protein-protein interaction plays an essential role in modulating salivary hypoxic responses. Further, hypoxia-induced salivary adaptive responses also appear to involve the phosphatidylinositol kinase-related kinase (PIKK) family members, such as ataxia telangiectasia mutate (ATM), implicating that hypoxia leads to cumulative DMA damage, rendering either cell survival or growth inhibition. Therefore, we hypothesize that salivary epithelial adaptive responses against hypoxia is mediated, at least in part, by an intricate balance among ATM activation, SUMO-dependent protein- protein interaction and its associated signaling, and PKC8 activation. To test our hypothesis, we propose the following three Specific Aims 1) To establish the role of SUMO-dependent protein modification in protecting salivary epithelial cells against hypoxia-induced injury; 2) To investigate SUMOylation-dependent and PKC5-mediated signaling network crosstalk upon hypoxic exposure and delineate the antagonistic role by PKC8-activation in programming SUMOylation-promoted hypoxia tolerance in salivary epithelial cells; and 3) To characterize SUMOylation targets that mediate the adaptive responses to hypoxia in salivary epithelial cells. The proposed mechanistic studies will extend our current knowledge on hypoxia-elicited pathogenesis in salivary glands. Information obtained from this study should lead to the development of innovative prevention and therapeutic approach against pathological manifestations in salivary glands, associated with Sjogren´s syndrome and head and neck irradiation
Keywords: Acute Disease; Apoptosis; ataxia telangiectasia mutated protein; Atrophic; Attenuated; attenuation; austin; base; Binding (Molecular Function); Biochemical; Biochemical Genetics; Biological; Biological Models; caspase; caspase-3; Cell Culture Techniques; Cell Cycle Arrest; Cell Cycle Progression; cell growth; Cell Hypoxia; cell injury; Cell model; Cell Survival; cell type; Cells; Characteristics; Chronic Disease; Deferoxamine; Development; Developmental Biology; DNA Binding; Elements; Engineering; Epithelial; Epithelial Cells; Equilibrium; Event; Exhibits; Experimental Models; extracellular; Family; Family member; Fluorescence Microscopy; GADD45; Genetic Transcription; Goals; Growth; Head and Neck Cancer; Head and neck structure; Health; Homeostasis; Homologous Gene; human ZNF45 protein; Hypoxia; In Vitro; Individual; Injury; innovation; insight; Introns; irradiation; Knowledge; Lead; Maintenance; Malignant Neoplasms; Mammalian Cell; MAP Kinase Gene; MAPK14 gene; Measurement; Mediating; member; Metabolic; mimetics; Molecular; Mus; Nature; novel; Nuclear; Oral; Oxygen measurement, partial pressure, arterial; Pathogenesis; Pathway interactions; Patients; Peptides; Phenotype; Phosphatidylinositols; Phosphorylation; Phosphotransferases; Physiological; Physiology; Play; Post-Translational Protein Processing; Prevention; Process; programs; Protein Kinase; protein protein interaction; Proteins; Proteomics; Radiation; Rattus; repaired; Repression; Research Personnel; Resistance; response; Rodent; Role; Saliva; Salivary; salivary adaptive responses; salivary cell; Salivary Glands; Scheme; Series; Signal Pathway; Signal Transduction; Sjogren`s Syndrome; Small Interfering RNA; Stimulus; Stress; System; Techniques; Testing; Therapeutic; Tight Junctions; Tissues; trafficking; Trans-Activation (Genetics); Transcriptional Activation; TRIM Motif; Ubiquitin; Whole Organism; Yang
Project start date: 2001-07-01
Project end date: 2012-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
5R01DE014183-10 (2011): $344085
5R01DE014183-09 (2010): $354727
MOLECULAR PROGRAMMING OF SALIVARY GLAND GENE EXPRESSION
K David
City Of Hope/beckman Research Institutecity: Duarte country: United States (us)
Grant 5R01DE010742-20 from National Institute Of Dental & Craniofacial Research
Abstract: Proper salivary gland function is critical for oral health. Radiation therapy for head and neck cancer often causes notable side effects that impact normal salivary gland function, most commonly xerostomia. Current therapies are unable to permanently restore salivary function, which remains a major therapeutic challenge. The long-term goal of our research is to elucidate the molecular and cellular mechanisms, in particular the signaling networks, involved in salivary gland homeostatic control and regeneration. One of the homeostatic control mechanisms, autophagy, is a constitutive cellular catabolic degradation process whereby cellular proteins and organelles are engulfed, digested through the lysosomal machinery and recycled. The autophagy-related 5 gene, Atg5, has been established as an indispensable player in autophagy. Our preliminary data suggest that acute hypoxic stress utilizes the JNK1/Beclin 1-dependent pathway to induce autophagy, providing transient protection against hypoxic stress-elicited cell death in salivary cells. Moreover, we generated Aqp5-Cre transgenic mice, in which the Cre recombinase was targeted to express in salivary acinar cells by being knocked in the exon 1 of Aquaporin-5 (Aqp5) gene, as Aqp5 protein is preferentially expressed in salivary acinar cells. Utilizing this knowledge and these tools, we propose to investigate the role of autophagy in governing homeostatic control, regeneration and adaptive responses following stress or injury of various types and/or severity to salivary acinar cells. Our central hypotheses are 1) Loss-of-Atg5-function impairs the ability of salivary acinar cells to maintain homeostatic control against stress (Aim 1), 2) Autophagy plays a transient cytoprotective role during injury (Aim 2), and 3) Crosstalk among autophagic, apoptotic and necrotic pathways decides the fate of stressed or injured salivary acinar cells (Aim 3). We postulate that autophagy protects salivary glands from stress and pathologic insults by promoting acinar cell survival and regeneration as a stress adaptation response. Our objective will be pursued through the following means (1) Characterize mice with salivary acinar-targeted Atg5 inactivation from crossing Aqp5-Cre mice with Atg5f/f mice, representing a unique source on which our experimental plan is based, (2) Determine the contribution of autophagy to homeostatic control using a chronic isoproterenol- injection model and to salivary acinar cell death and regeneration using a submandibular ductal ligation/de- ligation model, respectively, and (3) Investigate crosstalk of autophagy with other cell death pathways in underlying salivary adaptive responses. These studies will greatly improve our understanding of salivary gland homeostatic control and/or regeneration in a deleterious environment. In addition, they will provide a unique opportunity to evaluate the feasibility of autophagy-targeted therapies to ameliorate or restore salivary gland (dys)function following injury in human. Autophagy is a biological process, associated with cell death, which has important implications in normal physiology and many pathological conditions, including acute and chronic disease states and a myriad of cancers. Understanding how these autophagic processes modulate adaptation to cellular stress is essential for developing effective therapeutics to target diseased salivary tissues, as well as tissue engineering of salivary glands for tissue replacement. The proposed studies will not only open the field of salivary research, but will also assist in developing a strategy to prevent the loss of salivary gland function resulting from disease or cell death in head and neck cancer patients undergoing radiation therapy
Keywords: Acinar Cell; Acute; Acute Disease; Adopted; Adverse effects; Aging; Alleles; Apoptosis; Apoptotic; aquaporin 5; Area; Atrophic; Autolysis; Autophagocytosis; Autophagosome; base; Biological Process; Biomedical Research; Cell Death; Cell physiology; cell suicide; Cell Survival; Cells; Cellular Stress; Chronic; Chronic Disease; Data; Degenerative Disorder; Development; Digestion; Disease; Ductal; Enhancers; Environment; Epithelial Cells; Exons; extracellular; Failure (biologic function); Gene Expression; Genes; Goals; Head and Neck Cancer; head and neck cancer patient; Health; Homeostasis; Human; Hyperplasia; Hypertrophy; Hypoxia; Immunity; improved; In Vitro; in vivo; Injection of therapeutic agent; injured; Injury; innovation; insight; irradiation; Isoproterenol; Knock-in Mouse; Knowledge; Ligation; Maintenance; Malignant Neoplasms; Mammalian Cell; MAPK8 gene; Mediating; Modeling; Molecular; Mus; Natural regeneration; Nature; Necrosis; novel; Obstruction; Oral; Oral health; Organelles; Outcome; Pathologic; Pathway interactions; Patients; Phenotype; Physiological; Physiology; Play; pre-clinical; prevent; Process; programs; Promotor (Genetics); protein misfolding; protein structure; Proteins; public health relevance; Radiation therapy; recombinase; Recovery; Recycling; Research; response; Rodent; Role; Saliva; Salivary; salivary acinar cell; salivary adaptive responses; salivary cell; Salivary Gland Tissue; Salivary Glands; Severities; Signal Transduction; Sjogren`s Syndrome; Source; Starvation; Stimulus; Stress; Submandibular gland; Testing; theories; Therapeutic; Tissue Engineering; Tissues; tool; Transgenic Mice; Trauma; tumor progression; Withdrawal; Xerostomia
Relevance: NARRATIVE STATEMENT Autophagy is a biological process, associated with cell death, which has important implications in normal physiology and many pathological conditions, including acute and chronic disease states and a myriad of cancers. Understanding how these autophagic processes modulate adaptation to cellular stress is essential for developing effective therapeutics to target diseased salivary tissues, as well as tissue engineering of salivary glands for tissue replacement. The proposed studies will not only open the field of salivary research, but will also assist in developing a strategy to prevent the loss of salivary gland function resulting from disease or cell death in head and neck cancer patients undergoing radiation therapy
Project start date: 1993-09-01
Project end date: 2014-08-31
Budget start date: 1-SEP-2011
Budget end date: 31-AUG-2012
PFA/PA: PA-07-070
5R01DE010742-20 (2011): $396604
Sponsored Links Excellgen http://Excellgen.com
5R01DE010742-19 (2010): $408870
APPLYING GENERALIZABILITY THEORY TO THE MEASUREMENT OF EXTERNALIZING DISORDERS
K David
University Of Southern Mississippicity: Hattiesburg country: United States (us)
Grant 1R03HD061513-01A2 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: Project Summary State of the art diagnostic assessment procedures for externalizing disorders of childhood (i.e., ADHD and the disruptive behavior disorders) rely on reports from multiple informants (e.g., parents and teachers), often using multiple measures of the same construct, raising the challenge of how to interpret discrepant scores. Researchers and clinicians often use idiosyncratic decision rules for weighing the various reports, which is inconsistent with the recent attention and emphasis on evidence based assessment (EBA). By quantifying the degree of measurement consistency across types of raters, Generalizability Theory (GT) can provide an empirical basis for interpreting the results from multiple informants. Therefore, a GT study of the measurement of externalizing disorders can make a significant contribution toward the goal of EBA. The long- range goal is to maximize the measurement consistency of childhood externalizing disorders. The objective of this application is to quantify the degree of measurement error associated with parent and teacher ratings of childhood externalizing disorders using data for a community sample from the NICHD Study of Early Child Care and Youth Development (SECCYD) and for an archived clinical sample from The University of Alabama at Birmingham. These data are ideal, because they allow for multiple facets of measurement error that can be quantified by GT analyses. The first specific aim of this study is to partition the error variance in reports of externalizing symptoms across items, rater type, and grade (i.e., measurement occasion), as well as the interactions among these three facets. The second specific aim is to generate reliability estimates (Generalizability and Dependability coefficients) that incorporate all relevant sources of error. The third specific aim is to determine the generalizability of the various sources of information about these externalizing symptoms. All analyses will be conducted simultaneously for both ADHD and ODD behaviors in a multivariate analysis. Analyses will be replicated (for only one measurement occasion) with a clinical sample. The rationale for the study is that partitioning the error variance due to items, rater type, and grade will (a) determine which externalizing disorder (ADHD or ODD) are most reliably assessed by which informants, at which times, and thus (b) contribute to the further development of evidence based assessment. Childhood externalizing disorders are linked to negative consequences and thus accurate assessment and diagnosis is critical. One of the major challenges of such an assessment is resolving how to interpret discrepant scores from different sources. The proposed study will help determine the best way to integrate assessment data from multiple sources for use in the diagnosis of externalizing disorders, which will contribute to the further development of evidence based assessment
Keywords: Age; Alabama; Archives; Attention; Attention deficit hyperactivity disorder; base; Behavior; Child; Child Care; Child Psychiatry; Child Psychology; Childhood; Clinic; Clinical; Clinical Data; Communities; Data; Data Set; Development; Diagnosis; Diagnostic; Disease; Disruptive Behavior Disorder; Error Sources; evidence base; externalizing behavior; Goals; inattention; informant; instrument; Learning; Link; Measurement; Measures; Mothers; Multivariate Analysis; National Institute of Child Health and Human Development; Outcome; Parents; Participant; Procedures; Relative (related person); Reporting; Research Personnel; Respondent; Sampling; Source; Symptoms; teacher; Testing; theories; Time; Universities; Youth
Relevance: Childhood externalizing disorders are linked to negative consequences and thus accurate assessment and diagnosis is critical. One of the major challenges of such an assessment is resolving how to interpret discrepant scores from different sources. The proposed study will help determine the best way to integrate assessment data from multiple sources for use in the diagnosis of externalizing disorders, which will contribute to the further development of evidence based assessment
Project start date: 2011-04-01
Project end date: 2013-03-31
Budget start date: 1-APR-2011
Budget end date: 31-MAR-2013
1R03HD061513-01A2 (2011): $73250
PARKINSON DISEASE NEUROPROTECTION CLINICAL TRIAL
K David, Associate Professor Of Neurol.
Beth Israel Deaconess Medical Centercity: Boston country: United States (us)
Grant 5U10NS044482-09 from National Institute Of Neurological Disorders And Stroke
Abstract: No agent has been demonstrated unequivocally to have clinically significant neuroprotective efficacy in Parkinson´s disease (PD) patients; that is to slow or stop the ongoing loss of dopaminergic neurons and synapses. On the other hand, numerous agents have shown clear neuroprotective efficacy in vitro and in various in vivo models of PD, providing hope that effective neuroprotection can be achieved in PID patients. Selection of agents that target mechanisms of demonstrated pathogenetic significance in PD patients will improve the likelihood that this success in vitro and in vivo will translate into similar success in PD patients. Evidence has accumulated that mitochondrial dysfunction and oxidative stress may play key roles in the pathogenesis of PD. Mitochondrial complex I activity is impaired in the substantia nigra in PD compared to age-matched controls. The ability of complex I inhibitors (MPTP and rote) to reproduce many features of PD when systemically administered in animals indicates that complex I dysfunction may play a causal role in PD. Levels of markers of oxidative damage to lipids, proteins, and DNA are elevated in the substantia nigra in PD (as well as in MPTP-treated animals). Thus, complex I dysfunction resulting in oxidative stress may play a key role in the pathogenesis of PD. The parallel work on the role of alpha synuclein in PD also now is revealing a strong connection to mitochondrial mechanisms. Inhibition of complex I or exposure to oxidative stress promotes alpha synuclein aggregation. Conversely, overexpression of mutant or wild-type alpha synuclein induces mitochondrial dysfunction and oxidative stress, and expression of mutant alpha synuclein enhances susceptibility to oxidative stress. In vitro and in vivo models of PD have demonstrated successful neuroprotection with strategies to enhance energy metabolism, block free radical damage, or enhance endogenous antioxidant mechanisms. The clinical trial now being planned provides a unique opportunity to determine if similar strategies can yield clinically meaningful neuroprotection in PD
Keywords: (1)Benzopyrano(3, 4-b)furo(2, 3-h)(1)benzopyran-6(6aH)-one, 1, 2, 12, 12a-tetrahydro-8, 9-dimethoxy-2-(1-methylethenyl)-, (2R-(2alpha, 6aalpha, 12aalpha))-; 2-Amino-6-trifluoromethoxybenzothiazole; Abnormal Movements; advanced disease; Age; alpha synuclein; alphaSP22; Am 80; Am80; Amentia; Animal Model; Animal Models and Related Studies; Animals; anti-oxidant; Antioxidants; Benzoic acid, 4-(((5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)amino)carbonyl)-; Budgets; Caring; Clinic; clinical data repository; clinical data warehouse; clinical investigation; Clinical Research; clinical significance; Clinical Study; Clinical Trials; Clinical Trials Design; Clinical Trials, Unspecified; clinically significant; Complex; DA Neuron; Data Banks; Data Bases; data repository; Databank, Electronic; Databanks; Database, Electronic; Databases; Dementia; Deoxyribonucleic Acid; Diagnosis; DNA; Dopamine neuron; dopaminergic neuron; drug/agent; Drugs; Dysfunction; Dyskinesia Syndromes; Dyskinesias; Dyskinetic syndrome; Energy Expenditure; Energy Metabolism; enroll; Enrollment; Ensure; Exposure to; Free Radicals; Functional disorder; gene product; Human; Human, General; Idiopathic Parkinson Disease; improved; In Vitro; in vivo; in vivo Model; inhibitor; inhibitor/antagonist; Internist; language translation; Lewy Body Parkinson Disease; Lipids; Man (Taxonomy); Man, Modern; Medication; Mitochondria; mitochondrial; mitochondrial dysfunction; model organism; Motor; Movement Disorder Syndromes; Movement Disorders; mutant; NAC precursor; Neurologic; Neurological; Neurologist; Neuroprotectants; neuroprotection; Neuroprotective Agents; Neuroprotective Drugs; non A-beta component of AD amyloid; non A4 component of amyloid precursor; overexpression; oxidative damage; Oxidative Stress; Paralysis Agitans; PARK1 protein; PARK4 protein; Parkinson; Parkinson Disease; Parkinson`s; Parkinson`s disease; Parkinsonian; Parkinsonian Condition; Parkinsonian Diseases; Parkinsonian Disorders; Parkinsonian Syndrome; Parkinsonism; Parkinsons disease; Pathogenesis; pathophysiology; Patients; Pharmaceutic Preparations; Pharmaceutical Preparations; phase 3 study; Physiopathology; Play; Predisposition; Primary Parkinsonism; Proteins; recruit; Recruitment Activity; relational database; Riluzole; Role; Rote; Second Opinions; SNCA; SNCA protein; social role; Source; Substantia Nigra; Substantia nigra structure; success; Susceptibility; Synapses; Synaptic; Toxic effect; Toxicities; Translating; Translatings; Visit; Work
Project start date: 2002-09-30
Project end date: 2012-11-30
Budget start date: 1-DEC-2010
Budget end date: 30-NOV-2011
PFA/PA: RFA-NS-02-010
5U10NS044482-09 (2011): $97968
OXIDATIVE STRESS, ALPHA-SYNUCLEIN, AND MTDNA MUTATIONS IN PARKINSON´S DISEASE
K David, Associate Professor Of Neurol.
Beth Israel Deaconess Medical Centercity: Boston country: United States (us)
Grant 5R01NS058988-05 from National Institute Of Neurological Disorders And Stroke
Abstract: Mitochondrial complex I activity is impaired in Parkinson´s disease (PD), and inhibition of complex I with MPTP or rote reproduces many features of PD in animal models. The complex I defect can be transferred to cell lines expressing mitochondrial DNA (mtDNA) from PD patients, suggesting that mtDNA mutations account for the complex I defect. But despite attempts to identify them, the specific mutations that account for this defect remain unknown. Mitochondrial complex I dysfunction increases free radical production in the mitochondria, resulting in damage to macromolecules, with particularly high levels of potentially mutagenic damage to mtDNA. This damage to mtDNA accumulates with age and reaches especially high levels in PD. We hypothesize that this oxidative damage to mtDNA leads to the accumulation of somatic mtDNA mutations, ultimately contributing to the loss of dopaminergic terminals and potentially to cell death. Therefore, we predict that substantia nigra (SN) neurons will harbor high levels of somatic mtDNA mutations at early stages of PD. Consistent with this prediction, we present preliminary data indicating remarkably high levels of somatic mtDNA point mutations in SN neurons at very early stages of PD, whereas neurons with high levels of mutations are largely absent by end stage PD. Furthermore, we find that levels of the subset of mtDNA mutations predicted to result from oxidative stress are nearly 10-fold more prevalent in SN neurons from early PD compared to controls or to late PD neurons. These data are consistent with our hypothesis that somatic mtDNA mutations accumulate in SN neurons at early stages of PD, and that these mutations contribute to neuronal loss in PD. We further predict that experimental acceleration of the age-related accumulation of somatic mtDNA mutations will lead to similar changes in transgenic mice expressing a proofreading deficient mtDNA polymerase (POLG). We propose to use laser capture microdissection to analyze point mutations and large deletions in neurons and glia from human postmortem SN neurons and other brain regions in early PD, late PD, and controls. We further propose to conduct parallel experiments in transgenic mice expressing mutant POLG. Together, these studies have the potential to reveal a key mechanism in the pathogenesis of PD, and may lead to novel neuroprotective strategies. Parkinson´s disease (PD) is a common disorder that leads to progressive disability. Though many symptomatic treatments exist for PD, each has limitations, and a strategy to slow the progression of PD could have an enormous positive impact on the quality of life of PD patients. The proposed experiments will test the hypothesis that the accumulation of somatic mitochondrial DNA mutations in the brain contributes to the pathogenesis of PD, and may lead to novel strategies to slow the progression of PD
Keywords: Acceleration; Accounting; Age; age related; alpha synuclein; Animal Model; Astrocytes; Autopsy; base; Blood Platelets; Brain; Brain region; brain tissue; Cell Death; Cell Line; Cells; Cessation of life; Complex; Corpus striatum structure; Data; Defect; disability; Disease; disorder control; DNA; DNA Damage; DNA-Directed DNA Polymerase; Dopamine; Engineering; Free Radicals; frontal lobe; Functional disorder; Health; Human; immunoreactivity; laser capture microdissection; Lead; macromolecule; Measures; Microglia; Mitochondria; Mitochondrial DNA; mitochondrial DNA mutation; mitochondrial genome; Motor; mutant; Mutant Strains Mice; Mutation; Neuroglia; neuron loss; Neurons; novel; novel strategies; oxidative damage; Oxidative Stress; Parkinson Disease; Pathogenesis; Patients; Performance; Play; Point Mutation; Process; Production; Quality of life; Reporting; research study; Role; Rotarod Performance Test; Rote; Screening procedure; Series; Staging; Substantia nigra structure; Techniques; Testing; Time; Transgenic Mice; Tyrosine 3-Monooxygenase
Project start date: 2007-09-30
Project end date: 2012-03-31
Budget start date: 1-APR-2011
Budget end date: 31-MAR-2012
PFA/PA: PA-07-070
5R01NS058988-05 (2011): $267750
MITOPHAGY-DRIVEN SELECTION AGAINST HETEROPLASMIC MITOCHONDRIAL DNA MUTATIONS
K David, Associate Professor Of Neurol.
Beth Israel Deaconess Medical Centercity: Boston country: United States (us)
Grant 1R21NS077758-01 from National Institute Of Neurological Disorders And Stroke
Abstract: Disorders caused by maternally inherited pathogenic mitochondrial DNA (mtDNA) mutations can lead to a wide array of neurological, cardiac, and other disorders. Unfortunately, clearly effective clinical treatments for these often devastating disorders are lacking. An ideal strategy would eliminate the mutant mtDNA and replace it with wild type (WT) DNA. However, classic "gene therapy" approaches are difficult to apply to mtDNA mutations. On the other hand, mitochondria undergo frequent turnover (every few days), even in postmitotic cells, with only a subset of copies of the mitochondrial genome being replicated during this process, providing an opportunity to influence which mtDNA molecules are replicated. We now propose to test a novel strategy to promote the selective elimination of deleterious mtDNA mutations that can be applied to heteroplasmic mtDNA mutations. Heteroplasmy is a common feature of pathogenic mtDNA mutations, and refers to a mix of WT and mutant mtDNA within the same cells or tissue. Our hypothesis takes advantage of a natural cellular process known as "mitophagy" (mitochondrial degradation by autophagy), which is a mechanism for selectively eliminating dysfunctional mitochondria. We hypothesize that some mitochondria within a cell will harbor greater levels of a heteroplasmic mtDNA mutation than others. Those with greater levels of a deleterious mutation will tend to have relatively greater impairment of mitochondrial function. Therefore, we propose to test the novel hypothesize that stimulating mitophagy by inhibiting mTOR kinase activity in cells harboring a heteroplasmic pathogenic mtDNA mutation will drive selection against the mutant mtDNA, over time leading to a substantial reduction in the mutational burden and hence an improvement in mitochondrial function. We have a unique resource available for testing this hypothesis multiple SH-SY5Y cybrid cell lines harboring different levels of a heteroplasmic G11778A complex I (CI) gene mutation associated with Leber´s Heredity Optic Neuropathy (LHON), all prepared at the same time from members of a single family. Our preliminary data with these cell lines support our hypothesis. A second important resource in our laboratory is the "mutator" mouse that expresses a proofreading deficient mtDNA polymerase 3 (Polg) leading to accumulation with age of heteroplasmic somatic mtDNA mutations in association with a premature aging phenotype. Our preliminary data demonstrate substantial metabolic, behavioral, and neurochemical deficits in these mice. We now hypothesize that enhancing mitophagy in the Polg mutator mice will attenuate the accumulation of somatic mtDNA mutations and ameliorate the deficits in these mice. Ultimately, clinical applications of this strategy have the potential to be of benefit to patients with classic mitochondrial disorders associated with heteroplasmic mtDNA mutations, to families harboring Polg mutations associated with familial parkinsonism and other disorders, and potentially for age-related neurodegenerative disorders. Mitochondrial genetic disorders can be disabling but clearly effective treatments are lacking. Ideally, one would want to use a strategy that would eliminate the mutant mitochondrial DNA and replace it with normal DNA. We now propose to test a strategy of enhancing the natural process by which cells eliminate dysfunctional mitochondria, which we hypothesize will drive selection against mutant mitochondrial DNA in favor of normal DNA in cells harboring a mix of mutant and normal DNA
Keywords: Age; age related; Aging; Attenuated; Autophagocytosis; Behavioral; Blood - brain barrier anatomy; Brain; cancer therapy; Cardiac; Cardiomyopathies; Cell Line; cell motility; Cell physiology; Cells; Chronic; clinical application; Clinical Treatment; Clinical Trials; Cognitive deficits; Complex; Data; Defect; Disease; DNA; DNA Fingerprinting; DNA-Directed DNA Polymerase; Dose; effective therapy; Family; FDA approved; fly; Functional disorder; Gene Mutation; gene therapy; Genome; Hereditary Disease; Heredity; high risk; Human; human FRAP1 protein; Impairment; Inherited; kinase inhibitor; Laboratories; Lead; Longevity; member; Metabolic; Mitochondria; Mitochondrial Diseases; Mitochondrial DNA; mitochondrial DNA mutation; mitochondrial genome; Mus; mutant; Mutation; Myopathy; neurochemistry; Neurodegenerative Disorders; Neurologic; Non-Insulin-Dependent Diabetes Mellitus; novel; novel strategies; optic nerve disorder; Oral; Oxidative Stress; Parkinson Disease; Parkinsonian Disorders; Patients; Phenotype; Phosphotransferases; Premature aging syndrome; Process; Resistance; Resources; Role; Safety; Seizures; Sirolimus; stroke; Testing; Therapeutic; Time; Tissues; Translations; Work
Relevance: Mitochondrial genetic disorders can be disabling but clearly effective treatments are lacking. Ideally, one would want to use a strategy that would eliminate the mutant mitochondrial DNA and replace it with normal DNA. We now propose to test a strategy of enhancing the natural process by which cells eliminate dysfunctional mitochondria, which we hypothesize will drive selection against mutant mitochondrial DNA in favor of normal DNA in cells harboring a mix of mutant and normal DNA
Project start date: 2011-09-01
Project end date: 2013-08-31
Budget start date: 1-SEP-2011
Budget end date: 31-AUG-2012
PFA/PA: PA-10-069
1R21NS077758-01 (2011): $255080
CIRCADIAN CLOCK CELLS: AUTONOMY PERSISTENCE AND CALCIUM DEPENDENCE
K David, Assistant Professor
University Of California San Diegocity: La Jolla country: United States (us)
Grant 5R01MH082945-04 from National Institute Of Mental Health
Abstract: Daily oscillations in mammalian physiology and behavior persist even in a constant environment, and their disruption leads to jet lag, sleep disorders, and other maladies, including mood disorders. Such "circadian" (ca. 24 hr) rhythms depend on a biological clock located within the brain, in the suprachiasmatic nucleus (SCN). Most cells express "clock genes", components of a transcriptional feedback loop comprising the intracellular clock, but the SCN is the master pacemaker it has access to synchronizing light/dark input from the retina, specialized coupling mechanisms to maintain coherence among its component cellular oscillators and enhance its robustness, and neuronal efferent projections to synchronize cellular oscillators in peripheral tissues throughout the body. Recent work, however, has challenged the simplistic view that SCN neurons are all stable, autonomous, single cell transcriptional feedback oscillators. The objective of this proposal is to define the autonomy, persistence, and precision of SCN and fibroblast circadian clock cells, and to explore the interdependence of intracellular transcriptional, electrical, and calcium rhythms in these cells. This will be accomplished using mechanical, pharmacologic, and genetic approaches to disrupt cell interactions and manipulate membrane potential or intracellular calcium. Effects on the intracellular circadian clock will be assessed in individual cells by using optical methods to measure calcium and clock gene transcription, and multielectrode arrays to monitor neuronal firing. Specifically, we will test the hypotheses that (1) SCN neurons require tonic (but not rhythmic) input from other neurons to maintain rhythmicity, (2) apparent non-rhythmicity of some SCN neurons is a stochastic event due to membrane hyperpolarization rather than a reflection of a stable non-rhythmic subtype, and (3) cells require a tonic level of calcium (but not rhythmic calcium) for transcriptional or electrical rhythms. Answers to these fundamental questions about the cellular basis of circadian rhythmicity will be essential for an understanding of how circadian clocks contribute to health and disease, and serve as a basis for novel therapeutic approaches. PUBLIC HEALTH RELEVANCE A biological clock in the human brain keeps track of time of day and orchestrates countless circadian (ca. 24 hr) rhythms throughout the body. By further delineating the mechanisms of this clock at the level of single cells, the experiments proposed here may suggest new therapeutic approaches not only to jet lag, shift work, and other sleep disorders, but also to cancer, diabetes, and depression
Keywords: Address; Animals; Antibodies; base; Behavior; Biological Clocks; Bioluminescence; Brain; Buffers; Calcium; Calcium Oscillations; Calcium-Binding Proteins; Cell Communication; Cell physiology; Cells; Characteristics; circadian pacemaker; Circadian Rhythm Sleep Disorders; Circadian Rhythms; Clinical; Complex; Coupling; Crying; Defect; density; Dependence; Diabetes Mellitus; Disease; Dominant-Negative Mutation; Environment; Event; Explosion; Feedback; Fibroblasts; Fluorescence; Gene Components; Gene Expression; Genes; Genetic; Genetic Transcription; Health; Human; Image; Individual; insight; Jet Lag Syndrome; Label; Light; Liver; Malignant Neoplasms; Measurement; Measures; Mechanics; Membrane; Membrane Potentials; Mental Depression; Metabolic syndrome; Molecular; Monitor; Mood Disorders; Mus; Neuroglia; Neurons; Neuropeptides; novel therapeutic intervention; Optical Methods; Optics; Pacemakers; Parvalbumins; Periodicity; Peripheral; Phenotype; Physiology; Potassium; Process; Proteins; Records; research study; Retina; shift work; Signal Transduction; Signaling Molecule; Sleep Disorders; Slice; SNAP receptor; suprachiasmatic nucleus; Testing; Tetrodotoxin; Time; Tissues; Transfection; Variant; Work
Project start date: 2008-06-01
Project end date: 2013-02-28
Budget start date: 1-MAR-2011
Budget end date: 29-FEB-2012
PFA/PA: PA-07-070
5R01MH082945-04 (2011): $342411
MECHANISMS OF B CELL RESPONSES TO A NOVEL ADJUVANT FOR INFLUENZA VACCINE
K David, Clinical Fellow
Stanford Universitycity: Stanford country: United States (us)
Grant 5K08AI079269-04 from National Institute Of Allergy And Infectious Diseases
Project start date: 2008-07-01
Project end date: 2013-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
PFA/PA: PA-06-512
5K08AI079269-04 (2011): $130599