Identification of Self-renewal pathways in Cancer Stem Cells and Development of T

最近的证据表明，癌症有一个细胞层次结构，在这个层次中，癌症的少数群体 被称为癌症干细胞的细胞驱动肿瘤的生长和扩散。能够前瞻性地识别 致瘤癌细胞将有助于识别调节其生长、转移和 患者的存活率。以自我更新等基本过程中涉及的途径为目标可能会导致 更有效的治疗方法。初步证据表明，存在许多不同的基因。 由癌症干细胞及其非致瘤后代表达。这些基因中的许多都是mRNA 编码关键蛋白质和非编码微RNA被认为是调节基因表达/翻译的 被认为在基本的癌症功能中发挥作用，包括增殖、存活、自我更新和 对标准疗法的抵抗力。我们的研究首先是为了确定新的和更好的治疗方法 然后找出针对这些目标的药物。他们将依赖于体内(异种移植试验)和 体外(微流控技术用于单细胞基因表达、染色质免疫沉淀和细胞 (培养)方法，适应癌症干细胞具有挑战性的特殊性(稀有性和原发来源)。 以下目标将使我们能够实现这一目标。具体目标1.确定针对关键目标的药物 癌症干细胞靶点。具体目标2.确定调节活性氧的机制 癌症干细胞中的物种(ROS)。具体目的3.寻找其他肿瘤干细胞治疗靶点。 所有3个目标都将是项目1和项目3的合作努力，并将大量利用动物和流动 细胞学核心。目标2和目标3也将需要生物信息学核心才能成功

Recent evidence suggests that cancers have a cellular hierarchy in which a minority population of cancer cells, called cancer stem cells, drives the growth and spread of a tumor. The ability to prospectively identify tumorigenic cancer cells will facilitate the identification of pathways that regulate their growth, metastasis and survival in patients. Targeting the pathways involved in essential processes such as self renewal may lead to more effective therapies. Preliminary evidence demonstrates that there is a host of genes differentially expressed by the cancer stem cells and their non-tumorigenic progeny. Many of these genes, both mRNAs encoding critical proteins and non-coding micro RNAs thought to modulate gene expression/translation, are thought to play a role in essential cancer functions including proliferation, survival, self renewal and resistance to standard therapeutics. Our studies are designed first to identify new and better therapeutic targets and then to identify drugs against these targets. They will rely on both in vivo (xenograft assays) and in vitro (microfluidic technology for single cell gene expression, chromatin immunoprecipitation and cell culture) approaches, adapted to the challenging particularities of cancer stem cells (rarity and primary origin). The following aims will allow us to accomplish this goal. Specific Aim 1. To identify drugs that target critical cancer stem cell targets. Specific Aim 2. To determine the mechanisms which regulate reactive oxygen species (ROS) in cancer stem cells. Specific Aim 3. To identify other cancer stem cell therapeutic targets. All 3 aims will be a collaborative effort with both Projects 1 and 3 and will heavily utilize the animal and flow cytometry cores. Aims 2 and 3 will also require the bioinformatics core for success