Development of Nonhuman Primate Models for PSA Biology Studies

用于 PSA 生物学研究的非人类灵长类动物模型的开发

• 批准号: 7797648
• 负责人: James Nkambwe Mubiru
• 金额: $ 9.4万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7797648
• 关键词: Address; Affect; Age; Anatomy; Androgen Receptor; Animal Model; Benign Prostatic Hypertrophy; Biochemical; Biological Markers; Biology; Biomedical Research; Blood; Clinical; DNA; Development; Diagnosis; Disease; Doctor of Philosophy; Exons; Foundations; Genes; Genetic; Genetic Polymorphism; Genomics; Genotype; Goals; Hand; Histology; Individual; Macaca mulatta; Malignant neoplasm of prostate; Mentors; Modeling; Molecular; Monitor; Morbidity - disease rate; Obesity; Papio; Pathology; Phenotype; Population Genetics; Promoter Regions; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Receptor Gene; Relative (related person); Research; Scientist; Screening procedure; Sensitivity and Specificity; Serum; Study models; Training; Transgenic Mice; Trinucleotide Repeats; Variant; Veterinarians; career; interdisciplinary approach; mortality; nonhuman primate; professor; prostatitis; skills; structural biology; tool

DESCRIPTION (provided by applicant): Common prostatic diseases include prostate cancer, benign prostatic hyperplasia (BPH) and prostatitis. These diseases are a cause of significant mortality and morbidity. Prostate specific antigen (PSA) is released at increased levels into the blood early in the development of these diseases and therefore is widely used for screening, diagnosing and monitoring of prostate cancer. However, PSA has clinical limitations as a screen for prostatic diseases due to its low sensitivity and specificity. There is an urgent need for information about the causes of individual variation in serum PSA levels. The long term goal of this KO1 proposal is to prepare Dr. Mubiru for an independent career focused on the development of NHP models and tools for the study of PSA biology. Dr. Mubiru is a dual-trained veterinarian/scientist with DVM, MS and PhD degrees. He has been involved in the development of transgenic mice as well as in identifying biomarkers for prostate cancer. Dr Mubiru will acquire skills in molecular and population genetics as they relate to prostatic diseases. Dr. J. Rogers, a geneticist and genomics expert will serve as his mentor. Dr. Leach, a Professor in the Dept. of Cellular and Structural Biology at UTHSCSA will serve as co-mentor. Dr. Mubiru will specifically study the prostate of two nonhuman primate species (baboon, rhesus) maintained at the Southwest Foundation for Biomedical Research (SFBR). Our hypothesis is that 1) nonhuman primate species are the best animal models to study PSA biology, 2) serum PSA levels in nonhuman primates are genetically determined, 3) factors relating to adiposity and obesity affect serum PSA concentration. The specific aims of this proposal are i) study the anatomy and histology of the prostate of the baboon and rhesus, ii) investigate the influence of age and genetics on variation in PSA among these two species, iii) identify DNA polymorphisms in both the promoter regions of the PSA gene and exon 1 of the androgen receptor gene and assess the influence of these polymorphisms on variation in serum PSA levels, iv) investigate the relationship between obesity and its related phenotypes on one hand and serum PSA levels on the other. The aims of this proposal will be addressed using multidisciplinary approaches and through collaborative studies.

描述（由申请人提供）：常见的前列腺疾病包括前列腺癌，良性前列腺增生（BPH）和前列腺炎。这些疾病是死亡率和发病率显着的原因。前列腺特异性抗原（PSA）在这些疾病的发展早期以增加水平释放到血液中，因此被广泛用于筛查，诊断和监测前列腺癌。但是，由于其敏感性低和特异性，PSA具有临床局限性作为前列腺疾病的筛查。迫切需要有关血清PSA水平差异的原因的信息。该KO1提案的长期目标是为Mubiru博士做好准备，以致力于开发NHP模型和PSA生物学研究工具的独立职业。 Mubiru博士是DVM，MS和PHD学位的双重培训兽医/科学家。他参与了转基因小鼠的发展以及鉴定前列腺癌的生物标志物。 Mubiru博士将获得与前列腺疾病有关的分子和人口遗传学的技能。遗传学家和基因组专家J. Rogers博士将担任他的导师。 UTHSCSA的细胞和结构生物学系教授Leach博士将担任联合学。 Mubiru博士将专门研究在西南生物医学研究基金会（SFBR）维持的两种非人类灵长类动物（Baboon，Rhesus）的前列腺。我们的假设是1）非人类灵长类动物是研究PSA生物学的最佳动物模型，2）非人类灵长类动物的血清PSA水平是遗传确定的，3）与肥胖和肥胖有关的因素影响血清PSA浓度。该提案的具体目的是i）研究狒狒和恒河猴前列腺的解剖学和组织学，ii）研究年龄和遗传学对这两种物种中PSA变异的影响，iii）识别PSA基因和Exon pss pSA的启动子中的DNA多态性对这些psa受体的启动子的影响，并评估PSA级别的影响阶段的影响。一方面研究肥胖与其相关表型之间的关系，另一方面研究血清PSA水平。该提案的目的将使用多学科方法和协作研究来解决。