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MR IMAGING PREDICTORS OF RESPONSE & OUTCOME IN FIRST EPISODE SCHIZOPHRENIA

R Philip, Associate Director, Psychiatry Research
Feinstein Institute For Medical Researchcity: Manhasset    country: United States (us)

Abstract: There is now considerable evidence that anatomic pathology is present at the first episode of schizophrenia. Little research has been directed at understanding whether these anatomic deficits and their longitudinal course can be used to predict treatment response and neuropsychological and functional outcome measures. The identification of patients early in the course of illness who are nonresponsive to standard antipsychotic treatment could have significant implications for pharmacologic intervention and strategies for improving subsequent prognosis. Neurobiological predictors of treatment response in schizophrenia have not been well defined, however, and this phenomenon has no clear neurobiological basis, although a defect in the brain gray matter has been implicated. Moreover, recent empirical and theoretical work suggests that a defect in the brain white matter may be a contributing factor to antipsychotic nonresponse in schizophrenia. The investigation of neurobiological predictors in schizophrenia has been limited in large part due to the lack of controlled clinical trials from which to recruit patients and test hypotheses regarding response. Our preliminary data suggest that prefrontal gray matter deficits, as assessed via cortical surface mapping methods, predict treatment response in patients with first episode schizophrenia. Additional preliminary data suggest that lower fractional anisotropy, as assessed via diffusion tensor imaging, in frontotemporal regions is associated with treatment nonresponse in these patients. In the present study we propose scanning a unique group of 75 antipsychotic drug-naive, first episode schizophrenia patients. Patients will be drawn from an NIMH-sponsored (2R01-MH60004) double-blind randomized 12-week trial of risperidone vs. aripiprazole, and followed with regular assessments under controlled treatment as part of the CIDAR clinical algorithm for one year. The specific aims of this study are to (1) determine the relationship between cortical gray matter volume/density and white matter fractional anisotropy in first episode patients with schizophrenia and treatment response/outcome following the 12 week randomized clinical trial and after 52 weeks of controlled treatment; and (2) examine changes in gray matter volume/density and white matter fractional anisotropy in first episode patients over the 12 week randomized clinical trial and after 52 weeks of controlled treatment in relationship to treatment response/outcome. The identification of these abnormalities at the first episode of illness may be useful for identifying indicators of vulnerability, which may lead to improved early identification of individuals at risk for schizophrenia

Keywords: Algorithms; Anatomy; Anisotropy; Antipsychotic Agents; aripiprazole; base; Brain; Clinical; Clinical assessments; clinical care; Controlled Clinical Trials; Data; Defect; density; Diffusion Magnetic Resonance Imaging; Double-Blind Method; Drug Exposure; Early identification; experience; Exposure to; first episode schizophrenia; Functional disorder; functional outcomes; gray matter; Heterogeneity; improved; Individual; Intervention; Investigation; Knowledge; Lead; Left; longitudinal course; Longitudinal Studies; Magnetic Resonance Imaging; Maps; Methods; Modeling; National Institute of Mental Health (U.S.); Neurobiology; neuroimaging; neuropsychological; Outcome; outcome forecast; Outcome Measure; Pathology; Patients; prospective; Randomized; Randomized Clinical Trials; Recruitment Activity; Research; response; Risk; Risperidone; Sample Size; Scanning; Schizophrenia; Study models; Surface; Testing; Translating; treatment response; week trial; white matter; Work

Budget start date: 1-MAY-2011

Budget end date: 30-APR-2012

5P50MH080173-04_0002 (2011): $194727


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Grants awarded to R Philip

EFFECT OF BARIATRIC SURGERY ON MECHANISMS OF TYPE 2 DIABETES: THE B2D TRIAL

R Philip, Professor
Cleveland Clinic Lerner Col/med-cwrucity: Cleveland    country: United States (us)

Grant 5R01DK089547-02 from National Institute Of Diabetes And Digestive And Kidney Diseases

Abstract: This application is in response to RFA-DK-09-012 Pilot Studies for Studying the Mechanisms of Improvement in Type 2 Diabetes and Cardiovascular Risk Factors after Bariatric Surgery. Current estimates indicate that 11.3% of the US population have type 2 diabetes and in many US states over 30% of the population are obese. The identification of effective therapies for obesity and type 2 diabetes is clearly an urgent public health need. Roux- en-Y gastric bypass (RYGB) surgery represents a therapeutic approach that produces long term weight loss and may lead to the complete resolution of T2DM; such a finding holds exceptional significance for the management of this recalcitrant disease. RYGB is a bariatric procedure that involves stapling the upper stomach to reduce stomach capacity to 15-30 mls and bypassing the remaining stomach, duodenum and a small portion of the jejunum. We and others have shown that gastric bypass surgery has significant long-term effects on weight loss, the resolution of type 2 diabetes, and has a positive effect on cardiovascular risk factors in extremely obese patients. The objective of this application is to evaluate the effects of RYGB surgery on glycemic control and underlying mechanisms that contribute to type 2 diabetes in moderately obese subjects (BMI 30-40 kg/m2). Our central hypothesis is that RYGB surgery will reduce hyperglycemia by reversing 2-cell dysfunction and decreasing hepatic and peripheral insulin resistance. The Specific Aims are 1) to develop and implement a 12-month prospective randomized controlled clinical trial to test the effect of gastric bypass surgery versus advanced medical therapy and lifestyle on glycemic control in 60 obese patients with type 2 diabetes; 2) to determine the effects of gastric bypass surgery on pancreatic 2-cell function and incretin hormone secretion; and 3) effects on insulin sensitivity, ectopic lipid accumulation, and cellular signaling in skeletal muscle. The primary outcome variable is an HbA1c of d 6.5% at 12 months. Mixed meal tolerance tests will be used to assess changes in 2-cell function using an insulin/C-peptide kinetic modeling approach; and euglycemic hyperinsulinemic clamps will be used to evaluate insulin sensitivity. In addition, the underlying mechanisms will be explored by measuring incretin hormone responses (GLP-1/GIP), lipid accumulation in the liver and skeletal muscle using magnetic resonance spectroscopy, and insulin signaling pathways that regulate glucose uptake in skeletal muscle. The data that will be generated from the proposed studies will advance our understanding of the physiological mechanisms that link metabolic dysfunction in the pancreas, liver, and skeletal muscle with type 2 diabetes, and its resolution following bariatric surgery. The proposed trial will also provide important preliminary data to inform recruitment, retention, follow-up, and procedures for a longer-term trial that will compare surgery with advanced medical therapy, as we strive to identify the optimal treatment strategy to counter type 2 diabetes Treatment of obesity and type 2 diabetes is a major medical challenge. There is evidence that bariatric surgery is effective in producing long-term weight loss in extremely obese patients, and recent research suggests that it may also resolve type 2 diabetes. However, direct evidence of the glycemic benefits of bariatric surgery, specifically gastric bypass surgery, for patients with type 2 diabetes but who are not extremely obese is lacking, and the mechanisms that could make this happen are the subject of intense scientific debate. The proposed research will compare Bariatric Surgery with Intensive Medical Therapy using a randomized control trial in moderately obese patients with type 2 diabetes

Keywords: bariatric surgery; Bariatrics; base; Beta Cell; blood glucose regulation; Blood Pressure; Body Weight decreased; Bypass; C-Peptide; cardiovascular risk factor; Cell physiology; Cells; Consensus; Data; Diabetes Mellitus; diabetes prevention program; diabetes risk; Disease; Disease remission; Duodenum; effective therapy; experience; Fasting; fasting glucose; follow-up; Functional disorder; functional improvement; Gastric Bypass; Gastrostomy; Geographic state; glucagon-like peptide 1; Glucose; glucose uptake; glycemic control; Glycosylated hemoglobin A; GNAI2 gene; Health; Hepatic; Hindgut; human study; Hyperglycemia; incretin hormone; Insulin; insulin receptor substrate 1 protein; Insulin Resistance; insulin secretion; insulin sensitivity; insulin signaling; Insulin Signaling Pathway; jejunum; Kinetics; Lead; Life Style; lifestyle intervention; Lifestyle Therapy; Link; Lipids; Liver; Long-Term Effects; Magnetic Resonance Spectroscopy; Measures; Medical; Metabolic; Modeling; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Obesity; obesity treatment; Operative Surgical Procedures; Oral; Pancreas; Patients; Peripheral; Pharmacotherapy; Physiological; Pilot Projects; Population; post intervention; primary outcome; Primitive foregut structure; Procedures; prospective; public health medicine (field); public health relevance; Randomized Controlled Clinical Trials; Randomized Controlled Trials; randomized trial; receptor; Recruitment Activity; Regulation; Reporting; Research; Resolution; response; Risk; Role; Safety; Signal Transduction; Skeletal muscle structure; Stomach; Structure of beta Cell of islet; success; Testing; Therapeutic; Tracer; Treatment Efficacy; treatment strategy; tube feeding; Tyrosine Phosphorylation; Weight; Work

Relevance: Treatment of obesity and type 2 diabetes is a major medical challenge. There is evidence that bariatric surgery is effective in producing long-term weight loss in extremely obese patients, and recent research suggests that it may also resolve type 2 diabetes. However, direct evidence of the glycemic benefits of bariatric surgery, specifically gastric bypass surgery, for patients with type 2 diabetes but who are not extremely obese is lacking, and the mechanisms that could make this happen are the subject of intense scientific debate. The proposed research will compare Bariatric Surgery with Intensive Medical Therapy using a randomized control trial in moderately obese patients with type 2 diabetes

Project start date: 2010-07-14

Project end date: 2013-04-30

Budget start date: 1-MAY-2011

Budget end date: 30-APR-2012

PFA/PA: RFA-DK-09-012

5R01DK089547-02 (2011): $558243


3R01DK089547-02S1 (2011): $61753

ADMINISTRATIVE AND THEORY CORE

R Philip
Duke Universitycity: Durham    country: United States (us)

Abstract: The mission of the Administrative and Theory (A&T) Core is to facilitate research by the 20 members, 5 trainees, and 38 funded projects that comprise the Duke Transdisciplinary Prevention Research Center (TPRC). Six aims guide this Core, The first aim is to sustain and expand our multi-disciplinary intellectual community devoted to translational science in adolescent substance use prevention. During our initial tenure as a P20 Center, we have assembled faculty members from 8 administrative departments and 7 disciplines into a genuine community of scholars, the community will be nurtured by multi-disciplinary working groups, an active lunch bunch series, nationally prominent visiting speakers, meetings of advisory boards, an annual day-long retreat, an inviting physical location for investigators to congregate, a regular newsletter, research briefs, and a website. The second aim is to cultivate innovative theory about the development and prevention of adolescent substance use. This aim will be accomplished through a Faculty Fellows Seminar, in which 6 to 8 investigators across disciplines will commit to meet regularly to discuss a common theme or topic (e.g., methods to assess change, commonalities in regulatory process across levels, gene-environment interaction), for the purposes of developing collaborative research studies within the funded projects and proposing new projects. The third aim is to facilitate cross-project collaboration by assembling time-limited work groups composed of investigators from projects that share a common theme (e.g., the longitudinal studies of members Moffitt, Caspi, Dodge, Costello, Burton, Strauman, and Costanzo). Members of these work groups will meet regularly to consider common theory-testing, measurement, methods, or data analyses. The fourth aim is to nurture the training and career development of junior investigators, through participation in Core activities and support for career development awards and training programs. The fifth aim is to facilitate the administration and grants management of the funded, pending, and planned projects. The final aim is to evaluate the TPRC, through annual systematic surveys and an external review. The Administrative and Theory Core of the Duke Transdisciplinary Prevention Research Center will reduce the public health burden of adolescent substance use by supporting multi-disciplinary efforts by investigators to develop innovative theories and programs to prevent substance use

Keywords: adolescent substance use; career development; Collaborations; Commit; Communities; Data Analyses; Development; Discipline; Faculty; Funding; gene environment interaction; Grant; innovation; K-Series Research Career Programs; Location; Longitudinal Studies; Measurement; meetings; member; Methods; Mission; Newsletter; Prevention; Prevention Research; Process; programs; public health medicine (field); Research; Research Personnel; research study; Series; substance use prevention; Surveys; Testing; theories; Time; Training; Training Programs; Translational Research; Visit; web site; working group

Budget start date: 1-JUL-2011

Budget end date: 30-JUN-2012

5P30DA023026-04_9001 (2011): $490757


DUKE TRANSDISCIPLINARY PREVENTION RESEARCH CENTER

R Philip
Duke Universitycity: Durham    country: United States (us)

Grant 5P30DA023026-04 from National Institute On Drug Abuse

Abstract: The goal of the P30 Duke Transdisciplinary Prevention Research Center (TPRC) is to facilitate the translation of basic-science knowledge about regulatory processes and peer influences into innovative research efforts to prevent substance use and related problems in adolescents. During our initial five-year tenure as a NIDA-funded P20 TPRC, these themes have unified and catalyzed Center investigators who study the development and prevention of substance use at the intrapersonal, interpersonal, and institutional levels. As stipulated by NIH, a P30 Center does not directly conduct empirical investigations but, rather, exists to enhance funded projects and members. The TPRC has successfully initiated a broad intellectual community that includes 19 faculty members from 8 administrative departments and 7 disciplines, ranging from pharmacology and genetics to economics and sociology (plus 5 subdisciplines of psychology), who lead 25 externally funded collaborative research grants. Four specific aims guide this application. First, the TPRC will foster the innovative translation of theories across disciplines and projects, for the purposes of enhancing currently funded projects and generating new studies. Translation of theory will cross four steps of prevention science basic development, efficacy trials, effectiveness trials, and dissemination. Second, the TPRC will provide advanced methodological and data-analytic services to funded projects. Third, the TPRC will contribute to the nascent science of dissemination and implementation by discovering ways to influence practitioners, agency directors, school leaders, and policy makers to implement evidence-based prevention efforts at scale with fidelity. Theory in regulatory processes and peer influence will guide this effort. Finally, the TPRC will contribute to the training of the next generation of prevention scientists by enhancing ongoing funded training programs and by employing predoctoral and postdoctoral scholars-in training to serve as junior investigators in the cores. The TPRC will be evaluated internally and externally

Project start date: 2008-09-15

Project end date: 2013-06-30

Budget start date: 1-JUL-2011

Budget end date: 30-JUN-2012

5P30DA023026-04 (2011): $1321529


MECHANISTIC TARGETS FOR INTERVENTION IN SEPSIS-INDUCED RENAL INJURY

R Philip, Professor
University Of Arkansas Med Scis Ltl Rockcity: Little Rock    country: United States (us)

Grant 5R01DK075991-04 from National Institute Of Diabetes And Digestive And Kidney Diseases

Abstract: Renal failure is a frequent complication of septicemia that contributes significantly to mortality, particularly in postoperative patients in the ICU. In the U.S. septicemia is the 12th leading cause of death in adults and the 9th leading cause of death in children 1-4 years of age. Current therapy is, for the most part, only supportive. Thus, the long-term objective of our research is to identify new therapeutic targets to treat sepsis-induced renal injury. In this proposal, we will describe a functional defect in the kidney that may represent a previously unrecognized vascular pathway involved in polymicrobial sepsis- induced renal injury using the most clinically relevant murine model, cecal ligation and puncture (CLP). Our preliminary data show that inhibition of inducible nitric oxide synthase, inhibition of caspases, or inhibition of p53 each can prevent CLP-induced renal failure in mice. We also discovered a dramatic loss in perfused cortical peritubular capillaries following CLP that is ameliorated by these three classes of inhibitors. This unexpected and novel finding of a CLP-induced vascular defect mediated by reactive nitrogen species (RNS), caspases, and p53 is the basis of our central hypothesis that in sepsis, RNS-initiated activation of caspases results in a decline in peritubular capillary perfusion that leads to RNS-dependent tubular epithelial injury and ultimately renal failure. We will use biochemical and intravital videomicroscopy techniques to assess peritubular capillary dysfunction and tubular injury following mild and severe CLP in mice. Aim 1 will determine if peritubular endothelial injury and capillary dysfunction are early events that precede tubule epithelial cell injury. Aim 2 will determine the relative contributions of caspase-3 and p53 in peritubular capillary dysfunction and tubule epithelial cell injury using both pharmacological and genetic approaches. Aim 3 will determine if RNS-induced activation of p53 and caspases contribute to CLP-induced peritubular capillary dysfunction and tubule epithelial cell injury using pharmacological a genetic approaches. Both Aim 2 and Aim 3 will use in vivo studies as well as complementary in vitro studies with primary cultures of renal endothelial and tubular epithelial cells. These studies will supply valuable information on the cascade of signaling and cell- specific events that result in sepsis-induced renal injury. They will identify new signaling pathways and test them as new therapeutic targets for this devastating disease

Keywords: 4 year old; Acute Renal Failure with Renal Papillary Necrosis; Address; Adult; base; Biochemical; Blood capillaries; Blood Vessels; capillary; caspase; caspase-3; Cause of Death; Cell Culture Techniques; cell injury; Cells; Child; clinically relevant; Complication; cost; Data; Defect; Disease; Endothelial Cells; Endothelium; Enzymes; Epithelial; Epithelial Cells; Epithelium; Event; Evolution; Functional disorder; functional loss; Generations; Genetic; Health; Hour; human NOS2A protein; Immunohistochemistry; Impaired Renal Function; In Vitro; in vivo; inhibitor/antagonist; injured; Injury; Intervention; Kidney; Kidney Failure; Knockout Mice; Ligation; Mediating; Mediator of activation protein; Modeling; Mortality Vital Statistics; Motion; Mus; new therapeutic target; novel; overexpression; Pathogenesis; Pathway interactions; Patients; Perfusion; Postoperative Period; prevent; Protein p53; Puncture procedure; Reactive Nitrogen Species; Reactive Oxygen Species; Relative (related person); Renal function; Research; Role; Scheme; Sepsis; Septicemia; Serum; Signal Pathway; Signal Transduction; Stimulus; Superoxide Dismutase; Techniques; Testing; Tubular formation; Video Microscopy

Project start date: 2008-08-01

Project end date: 2013-05-31

Budget start date: 1-JUN-2011

Budget end date: 31-MAY-2012

PFA/PA: PA-07-070

5R01DK075991-04 (2011): $299907


3R01DK075991-02S1 (2010): $67063

5R01DK075991-03 (2010): $302936

MANIPULATING IMMUNODOMINANCE IN INFLUENZA HA

R Philip
Children´s Hospital Bostoncity: Boston    country: United States (us)

Abstract: Each influenza hemagglutinin (HA) is a mosaic of conserved and strain-specific epitopes, some of which are recognized by neutralizing antibodies. An influenza vaccine that preferentially elicits neutralizing antibodies that recognize conserved epitopes will be more broadly protective than those now in use. Understanding how the exposure history of subjects, differences in influenza vaccine antigens, and the addition of adjuvants bias the immune response towards different HA epitopes will enable us to design optimal vaccines. The following three hypotheses will be tested. (1] The B-cell repertoires elicited by non-replicating influenza vaccines and by infection differ in degree of polyclonal activation and breadth of neutralization. The repertoires elicited by adjuvanted and non-adjuvanted vaccines differ because adjuvant broadens the range of recognized epitopes. (2] Broadly reactive antibodies, including those recognizing the heterosubtypic stem epitope, are less frequent after true primary than after secondary influenza immunization due to broadening of the response by multiple HA stimulations. (3) Efficient induction of antibodies against a desired epitope requires (a] proliferation of a favorable germline antibody and (b) an affinity maturation pathway to a desired final specificity. There are preferred germline precursors and maturation pathways for antibodies targeting particular epitopes. Hypotheses 1 and 2 will be tested by mapping the epitopes recognized by the repertoires of human subjects with different exposure histories to influenza infection and/or immunization with adjuvanted or un-adjuvanted vaccines. We will seek broadly neutralizing antibodies (those we want to elicit) to understand their germline precursors and maturation pathways. We will also map the epitopes of the full range of antibodies that bind HA to determine what the humoral immune system "sees." The insights obtained from this mapping will be used to rationally design superior HA immunogens that will be optimized through an iterative cycle of antigen engineering, mouse immunization, repertoire analysis, and antigen redesign. Antigen design techniques will include selective epitope presentation, epitope masking, and germ-line antibody targetting followed by guided affinity maturation. The principles of antigen design revealed by this work could be applied to protective determinants of multiple pathogens for which vaccines are needed

Keywords: Activities of Daily Living; Adjuvant; Affinity; Antibodies; Antigens; B cell repertoire; Binding (Molecular Function); Child; Competitive Binding; Complex; design; Disease; Drug Formulations; Engineering; Epitope Mapping; Epitopes; Escape Mutant; Exposure to; Germ Lines; Hemagglutinin; high throughput screening; human subject; Immune response; Immune system; Immunization; improved; Infection; Influenza; Influenza Hemagglutinin; Influenza vaccination; Influenza virus vaccine; insight; Instruction; iterative design; Learning; Libraries; Maps; Masks; Memory B-Lymphocyte; Monoclonal Antibodies; Mus; neutralizing antibody; pandemic disease; pathogen; Pathway interactions; Plasmablast; Race; Recording of previous events; Resolution; response; Specificity; stem; Structure; Techniques; Testing; Time; Vaccine Antigen; Vaccines; Virus; Work

Relevance: RELEVANCE (See instructions): Influenza vaccines protect against strains closely related to the vaccine strains but not against more distantly related strains, necessitating repeated immunization with new flu vaccines and a race against time to make vaccines during pandemics. Learning how to design vaccine antigens that elicit antibodies that recognize relevant conserved patches on the influenza could allow more broadly protective vaccines against influenza and other diseases. This study aims to learn how to design these improved vaccine antigens

Project start date: 2011-08-01

Project end date: 2016-07-31

Budget start date: 1-AUG-2011

Budget end date: 31-JUL-2012

PFA/PA: PAR-10-271

1P01AI089618-01A1_8259 (2011): $554789


AIRWAY PROGENITOR CELL PROFILERATION AND DIFFERENTIATION DURING LUNG REPAIR

R Philip
Children´s Hospital Medical Center Cincicity: Cincinnati    country: United States (us)

Grant 1U01HL110964-01 from National Heart, Lung, And Blood Institute

Abstract: Airway Progenitor Cell Proliferation and Differentiation during Lung Repair This application responds to RFA-HL-12-006 to participate in a Consortium for the study of "Lung Repair and Regeneration." The proposal seeks to establish a participating Center working closely with other national "Consortium" members. Our proposed Center consists of faculty led by Dr. Jeffrey Whitsett at Cincinnati Children´s Hospital IVIedical Center (CCHMC) and Dr. Philip Streeter at the Oregon Health and Science University (OHSU), who have established collaborations for the study of lung biology. Our Center provides four specific aims, all focused to transcriptional mechanisms controlling proliferation and differentiation of Airway Epithelial Cell (AEC) progenitors. The Aims also generate and provide new antibodies, gene expression data and transgenic models of broad application to the field of Pulmonary Biology and Medicine. Aim 1 will elucidate the role of a novel transcriptional network controlling AEC progenitors and their differentiation in conducting airways, with focus to the role of a PAX9-centered transcriptional network in the regulation of basal cell proliferation and differentiation. Aim 2 will produce, characterize and use monoclonal and polyclonal antibodies for the identification and purification of human and mouse AECs for study of lung repair and disease. Aim 3 will define gene expression patterns and transcriptional regulators critical for AEC homeostasis with focus to PAX9 and associated factors. This Aim will create and standardize expression and transcriptional databases for human and mouse AECs and iPS cells induced to specific airway cell lineages. Aim 4 will produce novel transgenic mice for the conditional deletion and addition of genes in conducting AECs, including those related to the study of PAX9. Preliminary data accompanying this application were produced via close collaborations and interactions between members of laboratories in multiple divisions at CCHMC in the fields of Pulmonary Biology, Developmental Biology, Hematology/Oncology, and Bioinformatics, as well as those at OHSU and the Oregon Stem Cell Center. Our investigators have long-standing commitments and success related to the building and sharing of useful technologies and reagents and have been long committed to training others to advance the field of pulmonary biology and medicine. RELEVANCE (See instructions) This U01 grant seeks to provide (1) novel insights into the molecular and cellular control of AEC progenitors and their differentiation and (2) novel reagents, tools and procedures enabling scientific advancements of value to the field of pulmonary medicine

Keywords: Antibodies; Antibody Formation; Applications Grants; Basal Cell; base; Bioinformatics; Biology; cell behavior; Cell Culture Techniques; Cell Differentiation process; Cell Line; Cell Lineage; Cell model; Cell Proliferation; cell type; Cells; Cellular biology; Cessation of life; Collaborations; Commit; common treatment; Data; data modeling; Databases; Development; Developmental Biology; Diphtheria Toxin; Disease; Embryonic Development; Epithelial Cell Proliferation; Epithelial Cells; Epitopes; experience; Faculty; Flow Cytometry; Fluorescence-Activated Cell Sorting; Gene Deletion; Gene Expression; gene function; Generations; Genes; genetic analysis; Genomics; Grant; Health Sciences; Hematology; Histones; Homeostasis; Human; Immunization; Immunohistochemistry; in vitro Model; in vivo; induced pluripotent stem cell; insight; Instruction; interest; Laboratories; Lung; Lung diseases; Medical center; Medicine; member; Membrane; Messenger RNA; Modeling; Molecular; Molecular Profiling; Monoclonal Antibodies; mouse model; Mucous body substance; Mus; Mutation; Natural regeneration; NKX2H gene; novel; Nuclear; oncology; Oregon; Pathogenesis; Pathway interactions; Pattern; Pediatric Hospitals; polyclonal antibody; Principal Investigator; Procedures; Process; Production; progenitor; programs; Pulmonary Disease (Specialty); Reagent; Regulation; Regulator Genes; repaired; Reporter; Research; Research Personnel; RNA; Role; Scientist; Signal Transduction; skills; Specificity; Standardization; Stem cells; Structure of respiratory epithelium; success; Surface; Systems Biology; Technology; Testing; Tetracyclines; tool; Training; transcription factor; Transcriptional Regulation; transgene expression; Transgenes; Transgenic Mice; Transgenic Model; Universities; Work

Project start date: 2012-01-01

Project end date: 2016-12-31

Budget start date: 1-JAN-2012

Budget end date: 31-DEC-2012

1U01HL110964-01 (2012): $701050