Chemokine-related acute lung injury pathogenesis in African-American patients

非裔美国患者趋化因子相关的急性肺损伤发病机制

• 批准号: 8812903
• 负责人: Kirsten Neudoerffer Kangelaris
• 金额: $ 15.83万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8812903
• 关键词: Acute Lung Injury; Acute respiratory failure; Affect; African; African American; Algorithms; Anti-Inflammatory Agents; Anti-inflammatory; Antigen Receptors; Binding; Bioinformatics; Biological; Biological Factors; Biological Markers; California; Chromosome Mapping; Clinical; Clinical Data; Clinical Research; Cohort Studies; Critical Illness; Data; Diagnosis; Disease; Enrollment; Environmental Risk Factor; Epithelial; Erythrocytes; Etiology; Faculty; Foundations; Future; Gene Expression; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Predisposition to Disease; Genomics; Genotype; Goals; Health; Health Services Accessibility; Hospitalists; Incidence; Individual; Inflammation; Inflammatory; Injury; Interleukin-8; Interleukins; Kidney; Lead; Lung; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentors; Molecular Epidemiology; Not Hispanic or Latino; Organ failure; Outcome; Pathogenesis; Pathway interactions; Patients; Phenotype; Plasma; Play; Population; Population Control; Predisposition; Prevention strategy; Production; Prognostic Marker; Proteins; Reporting; Research; Research Infrastructure; Research Personnel; Risk; Risk Assessment; Role; San Francisco; Sepsis; Socioeconomic Status; Specimen; Techniques; Testing; Universities; Validation; Whole Blood; Work; base; career; chemokine; cohort; differential expression; experience; functional genomics; genetic variant; high risk; improved; innovation; lung injury; mortality; multidisciplinary; neutrophil; novel; outcome forecast; patient oriented; prospective; public health relevance; racial difference; racial disparity; response; skills; treatment strategy

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Kirsten Kangelaris, a hospitalist at the University of California, San Francisco. Dr. Kangelaris is establishing herself as a young investigator in patient-oriented clinical research in acute lung injury (ALI), with a focus on understanding biologic and genetic factors that impact susceptibility to and prognosis in acute lung injury among African-American patients. This K23 award will provide Dr. Kangelaris with the support necessary to accomplish the following goals: (1) to become an expert patient-oriented clinical and translational researcher in acute lung injury; (2) to elucidate genetic and biologic mechanisms of acute lung injury combining innovative approaches including genetics, protein markers and functional genomics; (3) to implement advanced biostatistical techniques in clinical studies, including advanced regression and bioinformatics; and (4) to develop an independent clinical research career. To achieve these goals, Dr. Kangelaris has assembled a multidisciplinary team comprised of a primary mentor, Dr. Michael Matthay, who has extensive experience in translational, pathogenesis-oriented ALI research, and in mentoring junior faculty to independent investigators, and two co-mentors: Dr. Elad Ziv, an expert in genetic mapping in admixed populations, and Dr. Bradley Aouizerat, a leader in genomics and molecular epidemiology. Additionally, Dr. Kangelaris will benefit from the expertise of several scientific advisors. Acute lung injury (ALI) is a common cause of acute respiratory failure in hospitalized patients, and African Americans suffer the highest ALI incidence and mortality rates. Dr. Kangelaris' research plan builds on her preliminary data to examine chemokine-dependent pathways of ALI pathogenesis in African-American patients. She will study the role of a functional polymorphism in the Duffy antigen/receptor for chemokines gene (Darc -46C/C, rs2814778), prevalent in individuals of African descent, that has been associated with worse ALI outcomes in her preliminary work, possibly via an increase in circulating interleukin (IL)-8. Dr. Kangelaris will test the extent to which this so-called "Dufy null" genotype is associated with susceptibility to acute lung injury (Aim 1), determine whether the Duffy null genotype is associated with differences in Duffy- binding chemokine levels (e.g., IL-8) and biomarkers of injury among patients with acute lung injury (Aim 2), and to use whole blood gene expression to identify chemokine-related pathways of acute lung injury pathogenesis in African-American patients (Aim 3). This research plan makes use of the existing infrastructure of Dr. Carolyn Calfee's Early Assessment of Renal and Lung Injury (EARLI) cohort at UCSF and Dr. Lorraine Ware's Validation of biomarkers in Acute Lung Injury Diagnosis (VALID) cohort at Vanderbilt University. This research will form the basis for an R01-level application to study the association between chemokine-related genomic and protein markers and acute lung injury susceptibility and outcomes in African-American patients.

描述（由申请人提供）：这是一份为加州大学旧金山分校的医院医生Kirsten Kangelaris博士申请的K23奖。Kangelaris博士是一名以患者为导向的急性肺损伤（ALI）临床研究的年轻研究者，专注于了解影响易感性的生物和遗传因素