MOUSE MODELS OF CANCER, BONE DISEASE, AND LACTATION

描述(改编自申请者的摘要)：K26奖将是 用于将50%的精力投入到小鼠病理生物学的研究和 指导兽医和兽医生物科学博士研究生 以及俄亥俄州立大学实验小鼠病理生理学的其他研究生课程 人类疾病的模型。将有四个主要研究项目：1) 建立乳腺特异的“基因敲除”模型以研究其功能 甲状旁腺激素相关蛋白(PTHrP)在哺乳期和乳汁中的变化 哺乳期间的新生儿(正在进行的项目)；2)调查 一种新的人类SCID/褐鼠恶性体液高钙血症模型 HTLV-1相关淋巴瘤(正在进行的项目)；3)研究发病机制 前列腺癌骨转移诱导骨形成的研究进展 异种前列腺上皮移植(“成骨细胞”转移) 裸鼠骨骼中的细胞(新项目)；以及4)检查 雌激素受体α和β基因的破坏(敲除) 正常、去卵巢和雌激素治疗的小鼠的骨重建(新 协作项目)。这些型号是经过精心挑选和开发的。 模仿人类疾病，提供获得知识的独特机会 并在人们知之甚少的领域培训小鼠病理生物学家，即 骨病、骨癌、骨质疏松症和体液高钙血症 恶毒。这些项目将建立在长期专业知识的基础上 申请人的骨、癌症和骨病理生理学的实验室 小鼠高钙血症。指导工作包括：1)担任以下项目的顾问 正在攻读实验小鼠病理生物学博士学位的兽医(目前 五个DVM的顾问)；2)担任研究的协作导师 兽医和基础科学家博士生在本系的项目 兽医生物科学(目前有17个项目)和博士生 分子、细胞和发育生物学课程与综合 俄亥俄州立大学癌症中心；3)参加由 转基因动物共享资源；4)合作研究项目 涉及小鼠的实验病理生物学；以及5)开发训练 小鼠病理生物学方面的程序。

DESCRIPTION (Adapted from the applicant's abstract): The K26 Award will be utilized to devote 50% effort to research in mouse pathobiology and to mentoring veterinarians and PhD graduate students in Veterinary Biosciences and other graduate programs at OSU in experimental pathophysiology of mouse models of human disease. There will be four major research projects: 1) develop a mammary gland-specific 'knock-out' model to investigate the function of parathyroid hormone-related protein (PTHrP) during lactation and in the neonate during suckling (ongoing project); 2) investigate the pathogenesis of humoral hypercalcemia of malignancy in a new SCID/beige mouse model of human HTLV-1-associated lymphoma (ongoing project); 3) investigate the pathogenesis of bone formation induced by bone metastases of human prostate cancer ("osteoblastic" metastases) by xenotransplantation of prostate epithelial cells in bones of athymic mice (new project); and 4) examine the effects of disruption (knock-out) of the genes for estrogen receptor alpha and beta on bone remodeling in normal, ovariectomized, and estrogen-treated mice (new collaborative project). The models have been carefully chosen and developed to mimic human disease and to provide unique opportunities to gain knowledge and train mouse pathobiologists in areas that are poorly understood, namely bone disease, cancer in bone, osteoporosis, and humoral hypercalcemia of malignancy. The projects will build on the long-term expertise of the applicant's laboratory in the pathophysiology of bone, cancer, and hypercalcemia in mice. Mentorship will consist of: 1) serving as advisor for veterinarians pursuing a PhD in experimental mouse pathobiology (currently advisor for five DVMs); 2) serving as collaborative mentor on research projects by veterinarians and basic scientist PhD candidates in the Department of Veterinary Biosciences (currently 17 projects) and PhD candidates in the Molecular, Cellular, and Developmental Biology Program and Comprehensive Cancer Center at OSU; 3) participating in training programs offered by the Transgenic Animal Shared Resource; 4) collaborating on research projects involving experimental pathobiology of mice; and 5) developing a training program in mouse pathobiology.