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: 7659832
• 负责人: James Nkambwe Mubiru
• 金额: $ 9.19万
• 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/7659832
• 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（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。这些疾病是造成重大死亡率和发病率的原因。前列腺特异性抗原 (PSA) 在这些疾病发展的早期以增加的水平释放到血液中，因此广泛用于前列腺癌的筛查、诊断和监测。然而，由于其敏感性和特异性较低，PSA作为前列腺疾病筛查存在临床局限性。迫切需要有关血清 PSA 水平个体差异的原因的信息。该 KO1 提案的长期目标是让 Mubiru 博士为独立职业做好准备，专注于开发用于 PSA 生物学研究的 NHP 模型和工具。 Mubiru 博士是一位接受过双重培训的兽医/科学家，拥有 DVM、硕士和博士学位。他参与了转基因小鼠的开发以及前列腺癌生物标志物的鉴定。 Mubiru 博士将获得与前列腺疾病相关的分子和群体遗传学技能。遗传学家和基因组学专家 J. Rogers 博士将担任他的导师。 UTHSCSA 细胞和结构生物学系教授 Leach 博士将担任联合导师。 Mubiru 博士将专门研究西南生物医学研究基金会 (SFBR) 饲养的两种非人类灵长类动物（狒狒、恒河猴）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 水平是由基因决定的，3) 与肥胖和肥胖相关的因素会影响血清 PSA 浓度。该提案的具体目标是 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个物种 PSA 变异的影响，iii) 识别 PSA 基因启动子区域和雄激素受体基因外显子 1 的 DNA 多态性，并评估这些多态性对血清 PSA 水平变异的影响，iv) 一方面研究肥胖及其相关表型之间的关系，另一方面研究血清 PSA 水平之间的关系。该提案的目标将通过多学科方法和合作研究来解决。