Adrenal Cortical Cell Therapy

描述（由申请人提供）： 我的长期职业目标是有一个学术地位，使我能够进行再生医学的研究，治疗婴儿和儿童的外科疾病，并教医学和研究生在实验室和临床病房。 我的短期职业目标是获得干细胞分子生物学方面的新技能和知识。研究职业发展计划包括实验室工作，指导，以及分子遗传学和干细胞生物学的精选课程。我选择了UCLA和我的导师Edward McCabe博士，因为他在人类遗传学和肾上腺发育的分子机制方面的专业知识，大学的资源，以及儿科和外科部门支持我培训的承诺。在科学咨询委员会的指导下，我将在培训期结束前过渡成为一名独立调查员。 拟议的研究重点是将肾上腺皮质细胞按其细胞表面标记物分类为亚群。使用在肾上腺皮质细胞中表达绿色荧光蛋白的转基因小鼠作为动物模型。在特定目标1中，将采用三组表面标志物，使用荧光激活细胞分选将肾上腺皮质细胞分离成亚群。将通过实时PCR测定其肾上腺特异性mRNA谱。在特定目标2中，基于其表面标志物的差异表达分选的肾上腺皮质细胞亚群将被移植到肾包膜下以确定其再生潜力。将评价再生组织支持肾上腺皮质功能的能力。这些研究将有助于更好地了解肾上腺皮质的发育，以及替代肾上腺皮质生理功能的新疗法。

DESCRIPTION (provided by applicant): My long-term career goal is to have an academic position that allows me to conduct research in regenerative medicine, to treat infants and children with surgical disorders, and to teach medical and graduate students in the laboratory and on the clinical ward. My short-term career goal is to acquire new skills and knowledge in stem cell molecular biology. The research career development plan includes laboratory work, mentoring, and selected courses in molecular genetics and stem cell biology. I have chosen UCLA and my mentor, Dr. Edward McCabe, because of his expertise in human genetics and molecular mechanisms of adrenal development, the resources of the university, and the commitment of the Departments of Pediatrics and Surgery to support my training. Under the guidance of the Scientific Advisory Committee, I will make the transition to become an independent investigator by the end of the training period. The proposed research is focused on sorting adrenal cortical cells into subpopulations as defined by their cell surface markers. A transgenic mouse that expresses the green fluorescent protein in adrenal cortical cells is used as the animal model. In Specific Aim 1, three sets of surface markers will be employed to separate adrenal cortical cells into subpopulations using fluorescence activated cell sorting. Their adrenal-specific mRNA profiles will be determined by real-time PCR. In Specific Aim 2, subpopulations of adrenal cortical cells sorted on the basis of their differential expression of surface markers will be transplanted under the renal capsule to determine their regenerative potential. The regenerated tissues will be evaluated for their ability to support adrenal cortical function. These studies will lead to a better understanding of the development of the adrenal cortex, as well as a new therapy that replaces the physiological function of the adrenal cortex.