OLFACTORY BULB CELL GENESIS AND SURVIVAL IN A MODEL OF REVERSIBLE DEAFFERENTATION
A Christine
Western Michigan Universitycity: Kalamazoo country: United States (us)
Grant 1R15DC011137-01A1 from National Institute On Deafness And Other Communication Disorders
Abstract: The overall aim of this proposal is to examine degeneration and regeneration of an adult brain structure, with the goal of better understanding the mature brain´s ability to heal after damage. We have developed a model for synaptic plasticity in the olfactory bulb in zebrafish one that produces temporary, partial deafferentation and allows potential regeneration of the adult brain to be observed. Repeated intranasal irrigation with Triton X-100 in this animal results in long-term, partial deafferentation of the olfactory bulb with a resulting deficit in bulb volume. Cessation of the detergent treatment allows the olfactory epithelium to recover and reinnervate the olfactory bulb, reversing the deafferentation-induced decrease in bulb volume. This proposal examines the mechanisms by which bulb volume is reduced and restored in this model. The hypothesis of this R15 proposal is that repeated chemical ablation of the olfactory epithelium produces deafferentation-related changes in cell genesis and cell survival in the olfactory bulb, and these effects are reversed with reinnervation by regenerated olfactory axons. Bromodeoxyuridine immunocytochemistry and TUNEL methods will be used to label newly formed cells and apoptotic cells, respectively. The first specific aim is to determine specific alterations in cell genesis and cell survival induced by repeated ablation of the olfactory epithelium with detergent. The hypothesis of this aim is that repeated assault on the olfactory epithelium by intranasal irrigation with detergent reduces the size of the olfactory bulb and this decrease in bulb size is possibly due to increased cell death and/or decreased cell genesis. Specific alterations in the patterns of cell genesis and cell survival will be analyzed to determine the effects of decreased afferent input on cell formation and cell fate. The second specific aim is to determine the effect of reinnervation on cell genesis and cell survival in the deafferented olfactory bulb. The hypothesis of this aim is that reinnervation will cause a reversal of the deafferentation-induced reduction in bulb size through decreased cell death and/or increased cell genesis. Zebrafish is used because it is an important model organism with similar basic cytoarchitecture as other vertebrates, including human, and the potential for future work on molecular mechanisms involved in brain plasticity. These studies permit investigation into the adult brain´s potential for recovery from physical or functional deafferentation due to injury or disease. This project examines the ability of the adult brain to recover from damage due to injury or disease. Cell genesis and cell death will be examined with a novel, reversible deafferentation method using repeated intranasal irrigation with detergent in zebrafish. This work will lead to a better understanding of the plasticity of the adult brain and the cellular interactions that are important in maintenance of adult brain structures
Keywords: Ablation; Adult; Afferent Neurons; Animal Model; Animals; Antibodies; Apoptotic; assault; Axon; Brain; Bromodeoxyuridine; Cell Death; Cell Survival; cell type; Cells; Chemicals; Deafferentation procedure; Detergents; Disease; Future; Goals; Healed; healing; Human; immunocytochemistry; In Situ Nick-End Labeling; Injury; insight; Investigation; Irrigation; Label; Laboratories; Lead; Maintenance; Methods; Modeling; Molecular; Natural regeneration; nerve supply; neurochemistry; novel; olfactory bulb; Olfactory Epithelium; Organ; Pattern; Peripheral; Quantitative Microscopy; Recovery; Regulation; reinnervation; restoration; spatial relationship; Structure; Synaptic plasticity; System; Triton X100; Vertebrates; Work; Zebrafish
Relevance: This project examines the ability of the adult brain to recover from damage due to injury or disease. Cell genesis and cell death will be examined with a novel, reversible deafferentation method using repeated intranasal irrigation with detergent in zebrafish. This work will lead to a better understanding of the plasticity of the adult brain and the cellular interactions that are important in maintenance of adult brain structures
Project start date: 2011-08-01
Project end date: 2014-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2014
PFA/PA: PA-10-070
1R15DC011137-01A1 (2011): $414135
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to A Christine
PROTEASE INHIBITOR RELATED DYSLIPIDEMIA
A Christine, Professor
Tufts University Bostoncity: Boston country: United States (us)
Grant 5R01HL065947-10 from National Heart, Lung, And Blood Institute
Abstract: This submission is the renewal of a project that was funded 6 years ago in response to an RFA that sought to determine the factors associated with cardiovascular disease in HI V-infected individuals. Our original project described predictors of abnormal surrogate markers of CVD (carotid intimal medial thickness and coronary calcium score) done at a 3 year interval. Antiretroviral regimens, markers of HIV disease activity, C- reactive protein and lipid profiles (including conventional lipid profiles, triglyceride-rich remnant lipoproteins, Lp(a), homocysteine, fasting blood glucose, free fatty acids and insulin levels), BMI, body composition by anthropometery , BIA and DXA as well as traditional risk factors (smoking, diet, blood pressure, age, gender, family history) were examined. Analyses from our original grant as well as others have suggested that traditional cardiovascular risk factors are the most common predictors for abnormal surrogate markers in this patient population; the impact of the dyslipidemia induced by Pis or other antiretroviral agents and the role of HIV and its associated inflammation on this increased risk remain unclear. To date no HIV surrogate marker studies have followed HIV-infected patients for the 6 year period that may be optimal detect the impact of the dyslipidemia or HIV on progression of disease in individuals. It remains clear that HIV infection itself induces low HDL-cholesterol levels and we have preliminary data that suggest that HIV infected individuals have an atherogenic HDL subpopulation profile. It appears that HDL-subpopulations may have a greater predictive value for risk of CVD than HDL-C alone. We now know that it is selected antiretroviral agents, not classes of agents, that are associated with more severe dyslipidemia in HIV-infected populations and propose to examine the impact of these agents (lopinavir/ritonavir, d4t, efavirenz) as well as traditional and emerging risk factors on HDL subprofiles and on surrogate markers of CVD. Markers of chronic inflammation are considered to be independent predictors of CVD; they also predict progression in HIV-infection and may reflect the cumulative burden of HIV disease in an infected individual. We propose to expand our studies of chronic inflammation adding CRP isoforms and sPLA2 to the determination of CRP to examine the association of these with atherogenic lipid profiles and with abnormal surrogate makers in our cohort. We propose to extend the duration of our surrogate marker studies in this continuation of our R01, to study the progression of c-IMT and coronary calcium score in an HIV infected population over 6 years and to document the changes in HDL subpopulations and inflammatory markers over the new grant period in our HIV infected cohort. The longitudinal determination of HDL subpopulations, the simultaneous determination of both cIMT and coronary calcium scores at 6 years in an HIV infected cohort are novel to this project
Keywords: Adult; Age; Anti-Retroviral Agents; antiretroviral therapy; Blood Glucose; Blood Pressure; Body Composition; C-reactive protein; Calcium; Cardiovascular Diseases; cardiovascular disorder risk; cardiovascular risk factor; Chronic; Cluster Analysis; cohort; Coronary; Data; Development; Diet; Dietary intake; Disease; Disease Progression; Dual-Energy X-Ray Absorptiometry; Dyslipidemias; efavirenz; Evolution; Family; Fasting; follow-up; Funding; Gender; Grant; High Density Lipoprotein Cholesterol; High Density Lipoproteins; HIV; HIV Infections; Homocysteine; Homocystine; Individual; Inflammation; inflammatory marker; Insulin; Lesion; Lipids; Lipoprotein (a); Lopinavir/Ritonavir; Measures; Medial; Monitor; sterified Fatty Acids; novel; Participant; patient population; Patients; Population; Predictive Value; premature; programs; Protease Inhibitor; Protein Isoforms; Proteins; Recording of previous events; Regimen; Research Personnel; response; Risk; Risk Factors; Risk Marker; Role; Smoking; Surrogate Markers; Technology; Thick; Time; Triglycerides; Viral Load result; Visit
Project start date: 2000-07-12
Project end date: 2012-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
5R01HL065947-10 (2011): $549775
NEMCH CLINICAL RESEARCH ON AIDS TRAINING GRANT
A Christine, Professor
Tufts Medical Centercity: Boston country: United States (us)
Grant 5T32AI007438-19 from National Institute Of Allergy And Infectious Diseases
Abstract: This competitive renewal proposal for an AIDS Clinical Training Grant from the Division of Geographic Medicine and Infectious Diseases (GMID) at the Tufts-New England Medical Center is submitted as an interactive program with the Brown University School of Medicine/ Miriam Hospital HIV program. Our goal is to continue to train investigators in methods of HIV/AIDS clinical research with an emphasis on the unique strengths of the two programs individually. These include nutritional and metabolic issues in HIV, cardiovascular risk in HIV, special populations in HIV including women, ethnic minorities, injection drug users, and incarcerated populations, outcomes research and decision analysis, international AIDS research, and clinical studies in HIV/AIDS. By teaching core methods together with mentored clinical research designed and carried out by trainees under the supervision of experienced and able mentors, we expect to train the next generation of AIDS clinical investigators to a level competitive for independent funding, so that their work and the work of the training grant will have a direct impact on and improve clinical practice and outcomes in HIV infected patients. We have requested 4 funded positions per year; each trainee has the option of electing a degree program in public health or in clinical research as well as conducting a mentored research project. Didactic training for trainees, whether they select a degree program, will emphasize basic methodology in study design. The faculty for this training grant is exceptionally well funded and many of the faculty have ongoing, productive collaborations in the form of a Center for AIDS Research (CFAR), a Fogarty International AIDS Training Program (AITRP) and a Center for Drug Abuse and AIDS Research (CDAAR). Through the mentoring system, the Executive Committee of the Grant, which included faculty from both institutions, and each trainee´s Research Coordination Committee, again including faculty from both institutions, we intend to individualize and optimize training opportunities for each trainee. An extensive evaluation process, including written reports and presentation of research results to the whole faculty of the training grant will ensure that each trainee is fully supported in his/her career development and that they take full advantage of the depth and breadth of the training opportunities offered
Keywords: Acquired Immunodeficiency Syndrome; Clinical Research; Grant; Training
Project start date: 1992-09-30
Project end date: 2013-08-31
Budget start date: 1-SEP-2011
Budget end date: 31-AUG-2012
PFA/PA: PA-06-468
5T32AI007438-19 (2011): $275626
THE IMPACT OF OMEGA THREE FATTY ACIDS ON VASCULAR FUNCTION AND CIMT IN HIV
A Christine, Professor
Tufts University Bostoncity: Boston country: United States (us)
Grant 5R01HL096585-03 from National Heart, Lung, And Blood Institute
Abstract: There is convincing evidence that there is an increased risk of cardiovascular disease in patients infected with HIV. There are multiple potential risks for CVD in HIV infected patients; atherogenic lipid profiles have long been associated with increased risk of cardiovascular disease; elevations in total and LDL cholesterol have been demonstrated to be associated with such increased risk in the general population. More recent data suggest that elevations in levels of triglycerides and decreased levels of HDL cholesterol may be equally important markers of CVD risk. There is also emerging data that CVD is an inflammatory disease, and that HDL-C levels and subprofiles are mediated by inflammation; in HIV-infected individuals these changes may be exacerbated by the HIV infection. While treatment of atherogenic lipid profiles is desirable, attempts to treat these abnormalities in HIV infection are complex in HIV infected individuals. In studies done in populations with and without HIV, intake of high doses of omega three fatty acids is demonstrated to decrease triglycerides and may have a beneficial effect on HDL-cholesterol levels. Intake of omega three fatty acids alters lipid metabolism and may decrease inflammation by decreasing production of arachidonic acid. At present, there are no data that extend these observations to determine whether intake of omega three fats over a more prolonged time period will also have a beneficial impact on vascular function and surrogate markers of CVD in HIV infected patients. We propose a randomized, double blind trial of purified omega three fatty acids in HIV infected individuals with elevated levels of triglycerides. While the impact of omega three fatty acids on lipid profiles should be evident within 12 weeks, we propose to conduct this trial for a full 24 months to test our overall hypothesis that this intervention will not only improve triglyceride and HDL-C levels, improve HDL- subprofiles and membrane phospholipids and decrease inflammation, but will also improve brachial artery reactivity as a measure of vascular function at 24 weeks and lead to a reduced rate of progression of cIMT as a surrogate marker of CVD at 24 months when compared to controls. The specific aims of this proposal include 1. to conduct a randomized, placebo controlled trial of omega three fatty acids over 24 months in HIV- infected individuals with elevated levels of triglycerides (> 150 mg/dl). 2. To demonstrate the impact of omega three fatty acid intake on TG levels and on HDL-C levels, HDL subprofiles, composition of membrane phospholipids, chronic inflammation as measured by CRP, sPLA2 and by levels of arachidonic acid. 3. To demonstrate the impact of omega three fatty acid intake on brachial artery reactivity at 24 weeks and on cIMT at 24 months. There is convincing evidence that there is an increased risk of cardiovascular disease in patients infected with HIV. Treatment of lipid abnormalities in HIV infection is difficult in HIV and studies suggest that intake of high doses of omega three fatty acids may safely improve lipids and decrease inflammation. We propose a randomized, double blind trial of purified omega three fatty acids in HIV infected individuals with elevated levels of triglycerides to test our overall hypothesis that this intervention will not only improve lipids and decrease inflammation, but will also improve vascular function at 24 weeks and lead to a reduced progression of surrogate markers of CVD at 24 months
Keywords: Anatomy; antiretroviral therapy; Arachidonic Acids; Blood Vessels; Body Composition; Body Weight; brachial artery; cardiovascular disorder risk; Cardiovascular system; Cell membrane; Chronic; Complex; Cytochrome P450; Data; Development; Diet; Disease; Dose; Double-Blind Method; Drug Interactions; Fatty acid glycerol esters; Fatty Acids; Fibrates; functional outcomes; General Population; HDL-triglyceride; Health; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Highly Active Antiretroviral Therapy; HIV; HIV Infections; improved; Individual; Inflammation; Inflammatory; Intake; Intervention; LDL Cholesterol Lipoproteins; Lead; Life Style; lipid metabolism; Lipids; Measures; Mediating; Membrane; Morbidity - disease rate; non-nucleoside reverse transcriptase inhibitors; Omega-3 Fatty Acids; Patients; Pharmaceutical Preparations; Phospholipids; Physical activity; Population; Production; Protease Inhibitor; Randomized; randomized placebo controlled trial; Relaxation; Risk; Smoking; Surrogate Markers; Testing; Thick; Time; Triglycerides
Relevance: There is convincing evidence that there is an increased risk of cardiovascular disease in patients infected with HIV. Treatment of lipid abnormalities in HIV infection is difficult in HIV and studies suggest that intake of high doses of omega three fatty acids may safely improve lipids and decrease inflammation. We propose a randomized, double blind trial of purified omega three fatty acids in HIV infected individuals with elevated levels of triglycerides to test our overall hypothesis that this intervention will not only improve lipids and decrease inflammation, but will also improve vascular function at 24 weeks and lead to a reduced progression of surrogate markers of CVD at 24 months
Project start date: 2009-08-20
Project end date: 2014-05-31
Budget start date: 1-JUN-2011
Budget end date: 31-MAY-2012
PFA/PA: PA-07-070
5R01HL096585-03 (2011): $729231
A Christine, Professor
Tufts University Bostoncity: Boston country: United States (us)
Grant 5R01HD057613-03 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: There are more than 40 million individuals infected with HIV living throughout the world, the majority of these live within the resource-limited world. It has been clear throughout the HIV epidemic that the nutritional status of the host plays an important, independent role in HIV-associated outcomes particularly progression of HIV disease and mortality. Although it would appear to be intuitive that maintenance of or improvement in nutritional status would lead to improved outcomes in HIV infected individuals, few data are available to demonstrate the potential benefits of maintaining nutrition status at normal. There are data that suggest that the use of micronutrients could reduce CD4 count decline and delay death, however micronutrients alone will not support or maintain nutritional status. The overall hypothesis of this application is that the consumption of a nutrient dense protein supplement (NDPS) early in HIV infection will slow disease progression, and that the time from infection with HIV to the initiation of HAART will be prolonged. If this hypothesis is proven to be correct, this type of intervention will result in benefit to the individual, as the need for the use of HAART would be delayed. It would also benefit the health systems, as cost savings would result from a delay in the initiation of HAART. Specifically we propose to enroll 740 HIV infected women in Kenya, with CD4 counts between 350 cells/
Keywords: Acquired Immunodeficiency Syndrome; Adherence (attribute); Adverse effects; Africa; antiretroviral therapy; bean; Body Weight decreased; CD4 Lymphocyte Count; Cells; Cessation of life; Communities; Consumption; cost effective; cost effectiveness; Cost Savings; Data; Dietary intake; Disease; Disease Progression; Effectiveness of Interventions; Enrollment; Epidemic; Fishes; Fruit; Health; Health system; Healthcare; Highly Active Antiretroviral Therapy; HIV; HIV Infections; HIV Seropositivity; improved; Individual; Infection; Intervention; Intervention Studies; Kenya; L Cells (Cell Line); Lead; Life; Maintenance; Malnutrition; Measures; Micronutrients; Morbidity - disease rate; Mortality Vital Statistics; Nutrient; nutrition; Nutritional status; Nuts; Opportunistic Infections; Outcome; Participant; Play; Pregnant Women; Proteins; public health medicine (field); Quality of life; Randomized; Randomized Controlled Trials; Recruitment Activity; Resources; Role; standard of care; successful intervention; Symptoms; Time; Visit; Weight; Woman
Relevance: Worsening nutritional status is common as HIV infection advances and contributes to poor outcomes. We propose an intervention to maintain and improve nutritional status in HIV-infected women in Kenya who are early in the course of their infection, in an attempt delay the progression of their HIV disease. We will randomize women to either a nutrient dense protein supplement (made from beans, nuts, dried fish and dried fruit) in a porridge that is already used in Kenya or to standard of care (no support of nutritional status) and determine whether the use of this porridge delays the need for participants to begin antiretroviral therapy; the public health implications of such an intervention, if successful, would be significant
Project start date: 2009-05-20
Project end date: 2014-04-30
Budget start date: 1-MAY-2011
Budget end date: 30-APR-2012
PFA/PA: RFA-HD-07-022
5R01HD057613-03 (2011): $304266
STRESS NEUROADAPTATIONS IN ALCOHOLISM
A Christine
University Of Wisconsin Madisoncity: Madison country: United States (us)
Grant 5F31AA018608-03 from National Institute On Alcohol Abuse And Alcoholism
Abstract: The primary goal of this project is to improve understanding of the changes in emotional behavior caused by alcoholism. Specifically, we will examine whether abstinent alcoholics demonstrate persistent change in their reactions to different types of stress-inducing stimuli. In the proposed project, alcoholics who have been abstinent for 4-8 weeks and non-alcoholic controls will view a series of visual stimuli separated into predictable shock blocks, unpredictable shock blocks, and no shock blocks. The shock blocks are proposed to model the emotional experiences of fear and anxiety, respectively. Auditory startle probes will be presented throughout the experimental session, and participants´ EMG activity will be recorded to index their physiological responses to the various stimuli. Based on our previous research and the extant literature, we predict that abstinent alcoholics, relative to non-alcoholic controls, will show increased startle potentiation in response to unpredictable shock (i.e. anxiety) but will show comparable levels of startle potentiation in response to traditional fear conditioning stimuli (predictable shock). We will follow-up with alcoholic participants after six months to assess their drinking behavior outcomes. These data, along with participants´ psychophysiological data will be used in exploratory analyses designed to consider their utility for predicting length of abstinence and likelihood of relapse. The study of emotional behavior in abstinent alcoholics is relevant to public health because alcoholism is a common, chronic, relapsing disorder which annually costs the US over $100 billion. The links between stress and drinking among problem drinkers are many, and further understanding of these mechanisms will help improve treatment decision-making and hopefully outcomes; this information may be of import to policymakers as well. The use of a cross-species procedure and dependent measure (i.e. the startle reflex) suggest that this particular research project can provide a critical link between preclinical work in this area and human addiction research
Keywords: Abstinence; ing; Acute; addiction; Affect; Affective; Affective Symptoms; alcohol abstinence; alcohol and other drug; Alcohol consumption; Alcohol dependence; alcohol use disorder; Alcoholism; Alcohols; Animal Model; Animals; Anxiety; Anxiety Disorders; Applied Research; Area; Attention; Auditory; base; Basic Science; Behavior; Benzodiazepines; biological adaptation to stress; Brain; Chemosensitization; Chronic; Cigarette; Clinical Research; clinically significant; conditioned fear; cost; Cycloserine; Data; Decision Making; design; Diagnostic and Statistical Manual; Disease; drinking; drinking behavior; Drug Addiction; Drug Exposure; Drug usage; Emotional; emotional experience; Emotions; Etiology; follow-up; Frequencies (time pattern); Fright; Goals; Homeostasis; Human; improved; indexing; Individual; Laboratories; Laboratory Research; Length; Light; Link; Literature; Measurement; Measures; Methods; Modeling; Nature; neuroadaptation; Neurobiology; Nicotine; non-alcoholic; Opiates; Outcome; Participant; Pharmaceutical Preparations; Physiological; Piper; positive emotional state; pre-clinical; Probability; problem drinker; Procedures; Process; programs; Property; Psychophysiology; public health medicine (field); Reaction; Reflex action; Relapse; Relative (related person); Reporting; Research; Research Project Grants; response; Risk; Role; Science; Series; Shock; Smoker; social; Stimulus; Stress; System; Testing; theories; Visit; visual stimulus; Walkers; Withdrawal; Work
Project start date: 2009-08-05
Project end date: 2012-08-04
Budget start date: 5-AUG-2011
Budget end date: 4-AUG-2012
5F31AA018608-03 (2011): $28381
ETIOLOGY OF TRANSLOCATIONS IN HEMATOPOIETIC CELLS
A Christine, Assistant Professor
University Of North Carolina Charlottecity: Charlotte country: United States (us)
Grant 4R01CA100159-07 from National Cancer Institute
Abstract: The long-term objective of my research is to understand the influence of hematopoietic-specific developmental programs on the repair DNA damage such as double strand breaks (DSBs) and the initial molecular events that lead to translocations, which are a hallmark of leukemia, lymphoma, and soft-tissue sarcomas. DSBs are highly recombinogenic, increasing the exchange of information between two homologous DNA duplexes by several orders of magnitude; thus, mammalian cells are potentially at risk for rearrangements arising during DSB repair. Chromosomal DSBs result following exposure to irradiation, alkylating agents, and topoisomerase II (topoII) inhibitors that are common therapies in the treatment of human cancers. Treatment regimens that include the topoII inhibitor etoposide are associated with one class of therapy-related acute myeloid leukemia (t-AML) and chromosomal translocations involving the mixed lineage leukemia (MLL) gene on chromosome band 11q23. Similarity of 11q23 MLL breakpoints in t-AML and infant leukemias suggests an association between de novo infant leukemia and in utero exposure to topoII inhibitors. The list of potential topo II inhibitors is extensive, and it remains unclear which of these compounds have a direct potential to induce the chromosomal translocations observed in the clinical setting. Using a unique genetic system to determine the potential for repair of DSBs within the breakpoint cluster regions of the 11q23 MLL gene and common partner genes to result in chromosomal translocations, this proposal will (1) determine the potential for exposure to a range of topoII inhibitors to initiate chromosomal rearrangements within the breakpoint cluster region of the MLL and AF9 genes similar to those observed in the clinical setting; and (2) create a targeted mouse model to determine in vivo the potential for exposure to topoII inhibitors to initiate chromosomal rearrangements within the breakpoint cluster region of the MLL and AF9 genes as measured by the presence of MLL-AF9 genome rearrangements in bone marrow and peripheral blood. These approaches in both ex vivo cell culture and in vivo mouse models will provide significant insight into the initiation of potentially oncogenic chromosomal rearrangements and leukemogenesis. Unraveling the etiology and consequences of translocations may lead to new approaches to therapy and prevention. Exposure to the topoisomerase II (topoII) inhibitors is associated with chromosomal translocations involving the mixed lineage leukemia (MLL) gene on chromosome band 11q23, one class of therapy-related acute myeloid leukemia (t-AML), and possibly de novo infant leukemias following in utero exposure to topoII inhibitors. The list of potential topo II inhibitors is extensive, and it remains unclear which of these compounds have a direct potential to induce the chromosomal translocations observed in the clinical setting. Our approaches in both ex vivo cell culture and in vivo mouse models will provide significant insight into the initiation of these oncogenic chromosomal translocations and leukemogenesis and may lead to new approaches to therapy and prevention
Keywords: 11q23; Alkylating Agents; Antigen Receptors; base; Bone Marrow; Cell Culture Techniques; Cells; chemotherapeutic agent; Chromosomal Rearrangement; Chromosomal translocation; Chromosome Band; Clinical; cohort; Development; DNA; DNA biosynthesis; DNA Damage; DNA Repair; DNA Sequence Rearrangement; Double Strand Break Repair; Embryo; embryonic stem cell; endodeoxyribonuclease SceI; Endonuclease I; Etiology; Etoposide; Event; Exposure to; Frequencies (time pattern); Generations; Genes; Genetic; Genetic Recombination; Genome; Genomics; Health; Hematopoietic; Human; in vivo; Infant; inhibitor/antagonist; insight; irradiation; Knock-in Mouse; Lead; leukemia; leukemia/lymphoma; leukemogenesis; Lymphoid Cell; Malignant Neoplasms; Mammalian Cell; Measures; Metabolism; MLL gene; MLLT3 gene; Molecular; Monitor; mouse model; Mus; novel strategies; Oncogenic; Perinatal Exposure; peripheral blood; Prevention therapy; programs; Recombinants; repaired; Reporter; Research; Risk; sarcoma; soft tissue; stem; Stem cells; System; Therapy-Related Acute Myeloid Leukemia; Topoisomerase II; Topoisomerase-II Inhibitor; Translocation Breakpoint; Treatment Protocols; Yeasts
Relevance: Exposure to the topoisomerase II (topoII) inhibitors is associated with chromosomal translocations involving the mixed lineage leukemia (MLL) gene on chromosome band 11q23, one class of therapy-related acute myeloid leukemia (t-AML), and possibly de novo infant leukemias following in utero exposure to topoII inhibitors. The list of potential topo II inhibitors is extensive, and it remains unclear which of these compounds have a direct potential to induce the chromosomal translocations observed in the clinical setting. Our approaches in both ex vivo cell culture and in vivo mouse models will provide significant insight into the initiation of these oncogenic chromosomal translocations and leukemogenesis and may lead to new approaches to therapy and prevention
Project start date: 2003-05-19
Project end date: 2013-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
PFA/PA: PA-07-070
4R01CA100159-07 (2011): $247644
FASEB SRC ON PROTEIN LIPIDATION, SIGNALING AND MEMBRANE DOMAINS
A Christine, Associate Professor
Federation Of Amer Soc For Exper Biologycity: Bethesda country: United States (us)
Grant 1R13CA162820-01 from National Cancer Institute
Abstract: The field of protein lipidation, signaling and membrane domains is an extremely active area of research as investigators seek to refine and expand our understanding of the consequences of protein-lipid interactions for cell signaling, growth and differentiation, and membrane synthesis and trafficking, and the role of these processes in human disease. We request funds to partially support the Federation of American Societies of Experimental Biology (FASEB) conference on "Protein Lipidation, Signaling and Membrane Domains", that will be held from July 24-29, 2011 in Saxtons River, Vermont. This meeting will highlight recent progress and provide a forum for critical discussions on these topics and promote interactions, idea-sharing, and collaborations between researchers from diverse fields ranging from biophysics and biochemistry to cancer biology, genetics, and clinical medicine. Lipid-modified proteins, signaling, and membrane domains represent distinct areas of research that are theless closely intertwined. For example, many lipidated proteins regulate membrane synthesis and vesicular trafficking. Moreover, lipidated proteins exhibit a strong yet dynamic interaction with membranes and their interaction with effector molecules and downstream signaling partners can be affected by shuttling in and out of membrane microdomains. Thus, investigators in these research areas benefit from and find synergy in discussions and collaborations initiated at this meeting. An equally important function of the meeting is to stimulate meaningful interactions between trainees including graduate students and postdoctoral fellows and established leaders in these fields. This objective is realistic given the small size of the conference (maximum 200 participants) and the requirement that speakers remain on-site throughout the meeting. We are also committed to fostering the career development of trainees. To this end, speakers chosen from submitted s will present seventeen short talks, with at least two-thirds selected from this cohort. Furthermore, we propose to offer 25 travel awards of $500 to highly qualified graduate students and postdoctoral fellows and give them each the opportunity to summarize the rationale, results, and importance of the work presented in their poster in a 5-minute oral presentation during the first poster session. In the selection process, we will ensure that the sessions are balanced with regard to the inclusion of women and underrepresented minority groups. We are requesting partial support for our scientific conference entitled "Protein Lipidation, Signaling and Membrane Domains", that will be held from July 24-29, 2011 in Saxtons River, Vermont. These research fields have emerged as important and integrated facets in the study of basic cellular biology and many human diseases, including cancer. It is essential to bring together researchers from these fields to share findings, exchange ideas, and initiate collaborations in order to better understand the biology of these cellular processes and develop effective treatments for diseases such as cancer
Keywords: ing; Affect; American; Area; Award; Biochemistry; Biology; Biophysics; Cancer Biology; career development; Cell physiology; Cellular biology; Clinical Medicine; cohort; Collaborations; Commit; Differentiation and Growth; Disease; effective therapy; Ensure; Equilibrium; Exhibits; Fostering; Funding; Genetic; graduate student; human disease; Lipids; Malignant Neoplasms; meetings; Membrane; Membrane Microdomains; Membrane Protein Traffic; membrane synthesis; Minority Groups; Oral; Participant; Postdoctoral Fellow; posters; Process; Proteins; Qualifying; Research; Research Personnel; Rivers; Role; Signal Transduction; Signaling Protein; Site; Societies; symposium; trafficking; Travel; Underrepresented Minority; Vermont; Woman; Work
Relevance: We are requesting partial support for our scientific conference entitled "Protein Lipidation, Signaling and Membrane Domains", that will be held from July 24-29, 2011 in Saxtons River, Vermont. These research fields have emerged as important and integrated facets in the study of basic cellular biology and many human diseases, including cancer. It is essential to bring together researchers from these fields to share findings, exchange ideas, and initiate collaborations in order to better understand the biology of these cellular processes and develop effective treatments for diseases such as cancer
Project start date: 2011-07-06
Project end date: 2012-06-30
Budget start date: 6-JUL-2011
Budget end date: 30-JUN-2012
PFA/PA: PA-10-071
1R13CA162820-01 (2011): $4000
QUANTITATIVE ANALYSIS OF AGING RETINA
A Christine, Professor
University Of Alabama At Birminghamcity: Birmingham country: United States (us)
Grant 5R01EY006109-23 from National Eye Institute
Abstract: The clinical management of patients with age-related maculopathy (ARM) has been revolutionized by non-invasive imaging of the retina at near-histological detail. Imaging is essential for educating patients about eye health and following disease progression, monitoring treatment outcomes, and specifying, designing, and validating new instruments. We propose translational research directed toward informing the clinical use of spectral domain optical coherence tomography (SD-OCT), which provides cross-sectional views of all chorioretinal layers, and fundus reflectance and autofluorescence (AF) imaging, which both provide en face (face on) views of the retinal pigment epithelium (RPE). We will exploit a unique resource of human donor eyes at different stages of ARM to produce gold standards for retinal image interpretation. Points of identification essential for maculopathy management and research using SD-OCT have not been systematically validated. We will obtain SD-OCT images of excised macula and optic nerve followed by high-resolution, wide-field histological cross-sections. Project MACULA (Maculopathy Unveiled by Laminar Analysis) will use aged normal, early ARM, geographic atrophy, and neovascular ARM to 1. Identify features in SD-OCT images and corresponding histological cross-sections of the same eyes, with special attention to disambiguating combined signals from adjacent layers and identifying ARM- pathology beyond drusen. 2. Measure the thickness of each retinal layer, Bruch´s membrane (BrM), and choroid across the macula and in comparison regions of peripheral retina. 3. Establish an electronic atlas of ARM pathology to inform next-generation tomographic imaging by scanning each tissue slide in its entirety and placing it an online digital pathology archive. The RPE, central to ARM pathogenesis, has been visualized clinically in the en face direction using both reflectance and autofluorescence (AF) signals, the latter from RPE lipofuscin. Project RPE Census will use chorioretinal whole mounts, DIC and confocal microscopy, and eyes of different ages and ARM status to 4. Quantify RPE packing geometry at well-specified locations to generate a continuous mathematical function describing RPE topography; describe disruptions over drusen and basal deposits. 5. Quantify RPE AF at well-specified locations; identify AF correlates of RPE disruptions associated with drusen and basal deposits, using 3-dimensional reconstruction of confocal microscopy images Improved knowledge about macular anatomy will help inform assessment of risk for advanced ARM and the assessment of treatments. We anticipate that data will be used by opinion leaders in clinical imaging, instrumentation engineers, ophthalmic educators and illustrators, and developers of new animal models of ARM. The fundamental data that we obtain will be useful for this and future generations of imaging. Because the retina is so readily visible through the eye´s optics, clinical imaging is now an essential component of staging and monitoring patients involved in clinical trials for treatments of age- related maculopathy (ARM), the large and debilitating cause of vision loss among the elderly. We propose to improve clinical interpretation of two increasingly common retinal imaging methods (optic coherence tomography and fundus autofluorescence) by quantitative analysis of retina and choroid from human tissue specimens at different stages of ARM
Keywords: 3-Dimensional; Age; Age related macular degeneration; Aging; Anatomy; Animal Model; Archives; Atlases; Attention; Benchmarking; Blindness; Bruch`s basal membrane structure; Censuses; Choroid; Clinical; Clinical Management; Clinical Treatment; Clinical Trials; Confocal Microscopy; Data; Deposition; design; digital; Disease Progression; disorder of macula of retina; Drusen; Elderly; Electronics; Engineering; Eye; Face; Fundus; Future Generations; geographic atrophy; Gold; Health; Human Resources; human tissue; Image; imaging modality; improved; instrument; instrumentation; Knowledge; Lipofuscin; Location; macula; Measures; Monitor; neovascular; next generation; normal aging; Optic Nerve; Optical Coherence Tomography; Optics; Pathogenesis; Pathology; Patient Monitoring; Patients; Peripheral; public health relevance; reconstruction; Research; Resolution; Retina; Retinal; Risk Assessment; Scanning; Signal Transduction; Slide; Specific qualifier value; Specimen; Staging; Structure of retinal pigment epithelium; Thick; Tissues; tomography; Translational Research; Treatment outcome
Relevance: Because the retina is so readily visible through the eye´s optics, clinical imaging is now an essential component of staging and monitoring patients involved in clinical trials for treatments of age- related maculopathy (ARM), the large and debilitating cause of vision loss among the elderly. We propose to improve clinical interpretation of two increasingly common retinal imaging methods (optic coherence tomography and fundus autofluorescence) by quantitative analysis of retina and choroid from human tissue specimens at different stages of ARM
Project start date: 1990-07-15
Project end date: 2013-05-31
Budget start date: 1-JUN-2011
Budget end date: 31-MAY-2012
PFA/PA: PA-07-070
5R01EY006109-23 (2011): $281280
BIOSTATISTICS AND BIOINFORMATICS CORE
A Christine, Associate Professor
University Of New Mexicocity: Albuquerque country: United States (us)
Abstract: The Biostatistics and Bioinformatics Core (BBC) provides support with design, data management and analysis of research studies for the University of New Mexico Interdisciplinary HPV Prevention Center (UNMIHPC). Moreover, it serves as a centralized resource for biostatistical consulting and analyses for all scientific projects proposed by the UNM-IHPC. The unit provides a centralized base to each of the four scientific research projects at all levels of investigation, beginning with the formulation of more specific hypotheses related to the overall unifying hypotheses, reviewing the design of studies, and evaluating the utility of measurement techniques. Support and consultation concludes with aiding in the interpretation, presentation, and final writing of results. The BBC also serves to warehouse and maintain a public health population-based data resource the New Mexico HPV Pap Registry (NMHPVPR), which under New Mexico Administrative code collects retrospective and longitudinal data from state-wide, regional and national laboratories on all cervical screening, diagnostic and treatment procedures. The BBC will promote the UNMIHPC research aims as follows 1) finalize the study designs and protocols in collaboration with each of the study investigators; 2) collaborate with the study investigators in the development of the forms and applications for recording data; 3) assist in development of protocols for data transmission; 4) collaborate with the study investigators in developing detailed Manuals of Procedures; 5) develop and manage the IHPC central and project-specific relational databases including the NMHPVPR; 6) run SAS quality-control program checks; 7) maintain a Master Database for each project with appropriate backups and security checks; 8) monitor study progress and distribute monthly study reports; 9) produce reports summarizing the status of data acquisition by subject, distributions and summary statistics for the primary variables; 10) interface and perform linkages to the New Mexico state-wide immunization information system (NM-SIIS); 11) perform basic and complex statistical analyses for the scientific projects as needed; and 12) develop and maintain the IHPC web site in collaboration with the UNM Health Sciences Center (UNM-HSC) web master
Keywords: base; Bioinformatics; Biological; Biometry; Cervical; Clinical; Code; Collaborations; comparison group; Complex; Consult; Consultations; Data; data acquisition; Data Analyses; data exchange; data management; Data Quality; database design; Databases; design; Development; Diagnostic; Diffusion; Drug Formulations; Effectiveness; Goals; Health Sciences; Human papilloma virus infection; Human Papillomavirus; Immunization; Information Systems; instrument; Internet; Intervention; Investigation; Laboratories; Manuals; Manuscripts; Measurement; Monitor; New Mexico; population based; Prevention; Procedures; programs; protocol development; Protocols documentation; public health medicine (field); Quality Control; Registries; relational database; Reporting; Research; Research Design; Research Personnel; Research Project Grants; research study; Resource Development; Resources; Running; Screening procedure; Security; Sexually Transmitted Agents; statistics; Summary Reports; Techniques; Universities; web site; Work; Writing
Relevance: The University of New Mexico Interdisciplinary STI Prevention Center will focus on the most common sexually transmitted agents, human papillomavirus (HPV) infections. To maximally realize improvements in HPV prevention, the Center will partner basic biological discovery, technological advancements, populationbased effectiveness and diffusion of interventions across laboratory, clinical & real-worid settings
Budget start date: 1-SEP-2011
Budget end date: 31-AUG-2012
5U19AI084081-03_6481 (2011): $393978
IMPROVING CANCER PAIN MANAGEMENT THROUGH SELF-CARE
A Christine, Professor
University Of California San Franciscocity: San Francisco country: United States (us)
Grant 5R01CA116423-06 from National Cancer Institute
Abstract: Recent work from our research group demonstrated that the use of a 6-week psychoeducational intervention, called the PRO-SELF Pain Control Program, compared to standard care, resulted in clinically and statistically significant improvements in pain management in a sample of oncology outpatients with bone metastasis. While the overall effects of the intervention were significant for approximately 70 percent of patients in the intervention group, pain intensity scores did not decrease by > 30 percent and worst pain intensity scores remained at or above 4 at the end of the intervention. Therefore, as a logical extension of this study, we propose a randomized clinical trial (RCT) that will test the effectiveness of two different doses of the revised PRO-SELF Pain Control Program [i.e., PRO-SELF PLUS-HIGH and PRO-SELF PLUS-LOW] on pain intensity and analgesic prescriptions. In addition, the sustainability of the two doses of the intervention will be evaluated. Adult oncology outpatients with pain from bone metastasis will be recruited, stratified by site and by whether or not they participate alone or with a family caregiver, and randomized to one of the doses of the intervention. The psychoeducational intervention will be conducted by specially trained oncology nurses and will include the components of knowledge, skills training, and coaching to improve cancer pain management. Patients in both groups will be seen in their homes over the course of 10 weeks with phone calls conducted in between the home visits. Patients in the HIGH-DOSE group will receive 6 visits and 10 phone calls [total time 12.3 hours]. Patients in the LOW-DOSE group will receive 4 visits and 6 phone calls [8.0 hours]. Follow- up visits to assess the sustainability of the intervention will be done at 2 weeks, 1 month, and 3 months after the intervention. Both quantitative and qualitative analyses will be conducted to evaluate patient outcomes. Lay summary - This study will test two different doses of an educational intervention to improve cancer pain management. In addition, the study will determine if the changes in pain management behaviors that the patients and their family caregivers learn continue to be used once the intervention stops
Keywords: Address; Adult; Analgesics; Anxiety; base; Behavior; behavior change; cancer pain; Cancer Pain Management; Clinical; Clinical Practice Guideline; Constipation; Critiques; Data; Dose; Educational Intervention; Educational process of instructing; Effectiveness; Effectiveness of Interventions; Enrollment; Evaluation; experience; Family Caregiver; Fatigue; follow-up; functional status; Funding; group intervention; Guidelines; Health Personnel; Home environment; Home visitation; Hour; House Call; improved; In complete remission; Intake; Intervention; intervention effect; Intervention Studies; Knowledge; Learning; Malignant Neoplasms; Mental Depression; Metastatic Neoplasm to the Bone; National Cancer Institute; Nurses; nursing intervention; Oncologic Nursing; oncology; Oncology Nurse; Opioid; Opioid Analgesics; Outcome; Outpatients; Pain; Pain management; partial response; Patients; Pattern; Problem Solving; Process; programs; psychoeducational intervention; Publishing; Qualitative Methods; Quality of life; Randomized; Randomized Clinical Trials; Recruitment Activity; Regimen; Reporting; Research; Research Personnel; Sampling; Self Care; Self Efficacy; Severities; Site; skills training; Sleep disturbances; standard care; Symptoms; Telephone; Testing; Time; Training; Translational Research; United States Agency for Healthcare Research and Quality; Visit; Work
Project start date: 2006-09-27
Project end date: 2012-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
5R01CA116423-06 (2011): $680065
Sponsored Links Excellgen http://Excellgen.com
TGF-BETA SIGNALING IN PANCREATIC CANCER PROGRESSION
A Christine, Associate Professor
Johns Hopkins Universitycity: Baltimore country: United States (us)
Grant 5R01CA140599-03 from National Cancer Institute
Abstract: Pancreatic cancer is an almost uniformly lethal disease. This year in the United States, an estimated 37,680 patients will be diagnosed with pancreatic cancer, and 34,290 patients will die of their disease. In contrast to the wealth of data demonstrating genetic or epigenetic alterations associated with pancreatic carcinogenesis, the genetic events specifically and consistently associated with pancreatic cancer metastasis have not been well defined. However, it is this final stage of the cancer process- the uncontrolled growth and/or dissemination of cancer cells to other organs-that is ultimately responsible for the majority of cancer-related deaths. This fact is of particular relevance to human pancreatic cancer. The dismal prognosis associated with this disease is largely due to the fact that most patients are diagnosed at an advanced stage of disease that is not amenable to surgical resection. Studies that focus on pancreatic cancer metastasis have the potential to greatly expand our understanding of the most lethal stage of this disease and identify novel areas for therapeutic intervention. We have recently characterized the patterns of pancreatic cancer failure in rapid autopsy participants and found that genetic inactivation of the DPC4 gene is highly correlated with widespread metastatic failure at autopsy. Thus, we propose three Specific Aims towards understanding the contribution of the TGF-b pathway to pancreatic cancer progression. First, we will perform high throughput sequencing and copy number evaluations of matched primary and metastatic tissues from 48 patients who have undergone rapid autopsy, and use this unprecedented dataset to identify the pro-metastatic genotype of pancreatic cancers. This genotype "classifier" will be independently validated in an independent set of early stage pancreatic cancer tissues from patients with known outcome. Second, we will determine the synergistic effects of TP53 and TGF-b pathway alterations in pancreatic carcinogenesis and progression using two well characterized mouse models of pancreatic cancer. Third, we will use well characterized cell lines derived from rapid autopsy patients to determine the effects of DPC4 restoration, or DPC4 knockout, on both canonical and non-canonical TGF-b pathway signaling and their relationship to invasion and spontaneous metastasis in vivo. These findings will be important because they will lead to improvements in therapeutic management of patients with pancreatic cancer based on their expected patterns of failure, including the development of novel rational therapies for this disease. Pancreatic cancer is an aggressive disease with a poor prognosis, in part because most patients are diagnosed at an advanced stage of disease. In this proposal we will study one of the most common pathways that control growth and normal development, the TGF-b pathway, and the mechanisms by which it is altered to promote pancreatic cancer formation and spread
Keywords: Aggressive behavior; Alleles; Area; Autopsy; base; cancer cell; cancer genome; carcinogenesis; Cell Line; Cessation of life; Collaborations; Collection; Critical Pathways; Data; Data Set; Development; Diagnosis; Diagnostic Neoplasm Staging; Disease; Disease Progression; Distant Metastasis; Epigenetic Process; Evaluation; Event; Excision; Failure (biologic function); Genes; Genetic; Genetic Status; Genotype; Goals; Growth; Health; Human; in vivo; inhibitor/antagonist; innovation; Knock-out; KRAS2 gene; Laboratories; Lead; MADH4 gene; Malignant neoplasm of pancreas; Malignant Neoplasms; Manuscripts; Mediator of activation protein; Modeling; mouse model; mutant; Mutation; Neoplasm Metastasis; new therapeutic target; novel; novel therapeutic intervention; Operative Surgical Procedures; Organ; Outcome; outcome forecast; Pancreas; pancreatic cancer cells; Pancreatic carcinoma; Participant; Pathway interactions; Patients; Pattern; Predictive Value; Primary Carcinoma; Principal Investigator; Process; programs; Publishing; Reporting; Research; Research Personnel; Resected; Resources; restoration; Science; Sequence Analysis; Signal Pathway; Signal Transduction; Stage at Diagnosis; Staging; Systems Biology; Therapeutic; Therapeutic Intervention; Tissues; TP53 gene; Transforming Growth Factor beta; Treatment Failure; Treatment Protocols; tumor progression; Tumorigenicity; United States; Work
Relevance: Pancreatic cancer is an aggressive disease with a poor prognosis, in part because most patients are diagnosed at an advanced stage of disease. In this proposal we will study one of the most common pathways that control growth and normal development, the TGF-¿ pathway, and the mechanisms by which it is altered to promote pancreatic cancer formation and spread
Project start date: 2009-09-01
Project end date: 2014-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
PFA/PA: PA-07-070
5R01CA140599-03 (2011): $330091
DIFFERENTIAL RESPONSE TO THE DPP MORPHOGEN
A Christine
New York Universitycity: New York country: United States (us)
Grant 5R01GM063024-09 from National Institute Of General Medical Sciences
Abstract: In all animals the initial events of embryogenesis are controlled by maternal gene products that are deposited into the developing oocyte. At some point after fertilization, control of embryogenesis is transferred to the zygotic genome in a process called the maternal to zygotic transition (MZT). During this time maternal RNAs are degraded and zygotic RNAs are transcribed. Although progress has been made on the mechanisms underlying RNA degradation (Giraldez et al., 2006), the activators of the zygotic genome have remained elusive. A hint came from the discovery that many Drosophila zygotic genes share a cis-regulatory motif related to CAGGTAG (ten Bosch et al.,2006; De Renzis et al., 2007). We recently isolated a zinc-finger protein, Zelda, which binds specifically to these sites. Mutant embryos lacking maternal zelda transcripts fail to activate the transcription of a sample of zygotic genes, and are defective in several aspects of the cellularization process, which corresponds to the point at which embryos can no longer survive on maternal products alone (Merrill et al., 1988). Our preliminary results suggest that Zelda activates batteries of genes during the MZT, each responsible for a key developmental process. Zelda may activate early-transcribed microRNAs that mediate maternal RNA degradation, thus providing a link between the two hallmark events of the MZT. Building on our preliminary data, we will further characterize the role of Zelda in the MZT. How many genes does Zelda activate and which early genes are independent of Zelda? We will use a genomics approach in Aim 1 to determine all Zelda targets in the early embryo. How many genes does Zelda activate, and are there groups of genes not regulated by Zelda? In Aim 2 we ask whether Zelda plays an instructive or permissive role, or both, in activating target genes, and how it interacts with other key regulators such as Dorsal and Dpp to activate their target genes. In Aim 3 we investigate the structure and function of conserved Zelda protein domains, and test whether there is Zelda function in the long germ Nasonia wasp and if it plays a similar role in activating the zygotic genome. Finally, we address mechanistic questions regarding the timing of genome activation in Aim 4, and the possible role of Zelda in reversing the initial silencing of the genome. The experiments outlined in this proposal have the potential to advance greatly our understanding of the mechanisms underlying the MZT. The study of the molecular mechanisms underlying basic developmental processes is relevant to understanding the cause and progression of human diseases such as cancer, and human disorders such as birth defects
Keywords: activating transcription factor; Address; Affect; Affinity; Amino Acids; Animals; Antibodies; Binding (Molecular Function); Biological Assay; blastocyst; Candidate Disease Gene; Chimeric Proteins; Chromatin; Congenital Abnormality; Data; Dependence; Deposition; Development; Developmental Process; Disease; DNA Binding; DNA Polymerase II; Dorsal; dorsal proteins; Drosophila genus; Embryo; Embryonic Development; Enhancers; Event; Fertilization; Gene Activation; Gene Dosage; Gene Expression; Gene Targeting; Genes; Genetic Transcription; Genome; Genomics; Germ; Histones; Human; human disease; Insecta; interest; Life; Link; Malignant Neoplasms; Mediating; MicroRNAs; Molecular; Molecular Profiling; morphogens; mutant; Mutate; Nucleic Acid Regulatory Sequences; Oocytes; Phenotype; Play; Positioning Attribute; Process; Promotor (Genetics); Proteins; public health relevance; Reporter Genes; research study; response; RNA; RNA Degradation; RNA Interference; Role; Sampling; Site; Smad protein; Smad Proteins; Staging; Structure; Tertiary Protein Structure; Testing; Time; Transcript; Wasps; Zinc Fingers
Project start date: 2002-04-01
Project end date: 2012-04-30
Budget start date: 1-MAY-2011
Budget end date: 30-APR-2012
PFA/PA: PA-07-070
5R01GM063024-09 (2011): $266053