Shawn Bratton
副教授
德克萨斯大学医学博士安德森癌症中心
表观遗传学和分子癌变系
布拉顿实验室,我们主要是兴趣sted in two basic areas of research: apoptosis (programmed cell death) and autophagy (self-cannibalism). Apoptosis is critical for normal development in multicellular organisms from flies to humans, and it works in concert with cell division to maintain the normal size and function of adult tissues. Diseases associated with increased rates of apoptosis, include neurodegenerative disorders (Alzheimer's Disease and Parkinson's Disease), AIDS, myelodysplastic syndromes, and ischemic injury (stroke and myocardial infarction), whereas those associated with inhibition of apoptosis, include autoimmune diseases and cancer. In fact, defective apoptosis is a hallmark of cancer and a major cause of resistance during cancer therapy. Autophagy, on the other hand, is primarily a cell survival rather than a cell death process. In cells deprived of growth factors or nutrients, intracellular proteins and even entire organelles are broken down and proteolytically digested within lysosomes in order to provide energy and macromolecules for essential biosynthetic pathways. Autophagy therefore plays an important role during tumorigenesis, and it promotes chemoresistance by allowing tumor cells to remove damaged proteins and organelles. Finally, emerging evidence suggests that cross-talk exists between apoptotic and autophagic pathways, in that established regulators of apoptosis, such as the tumor suppressor p53 and antiapoptotic Bcl-2 family members, also regulate autophagy.
Projects/Techniques：下面，我在实验室中提供了一些正在进行的项目。我们利用广泛的技术来解决生物学上重要的问题，包括重组蛋白工程和表达，各种分子生物学方法（例如PCR，克隆，诱变，RT-PCR），细胞培养，流式细胞术，荧光显微镜以及生成新颖的鼠标模型。
caspase激活复合物: Most toxicants induce apoptosis by triggering the activation ofcaspases（半胱氨酸天冬氨酸特异性蛋白酶）。引发剂胱天蛋白酶通过与特定的衔接蛋白的关联而激活，然后激活效应子胱天蛋白酶，从而裂解细胞蛋白并拆除细胞。因此，胱天蛋白酶是通过唯一的信号转导途径激活的，我们的总体目标是从分子细节中理解这些胱天蛋白酶的激活方式以及如何调节它们的活动。我们对一个称为的多聚体综合体特别感兴趣apoptosome。这个大型综合体 - 七个APAF-1(apoptosis protease-activating factor-1) proteins and formed in response to mitochondrial stress—binds to the initiator caspase-9 to form a holoenzyme that subsequently activates the effector caspases-3 and -7. We are currently studying the regulatory mechanisms that control the activity of this complex体外and体内。
Inhibitor of apoptosis (IAP) proteins and IAP antagonists: IAPs are important antiapoptotic proteins present throughout nature. In humans and rodents, at least one family member,XIAP（X连锁IAP），是caspases -9，-3和-7的已建立抑制剂。但是，目前尚不清楚其他家庭成员如何抑制细胞凋亡。我们目前正在研究其他IAP的机制，例如细胞IAP1（CIAP1）和CIAP2， 也Drosophila IAP-1（DIAP1）和DIAP2, suppress apoptosis in human and fly models of cell death. The fly IAP antagonists,收割者，隐藏（头部不足有缺陷），严峻，镰刀，anddOmi, are thought to induce apoptosis during development by antagonizing DIAP1. Recent studies in our laboratory and others, however, suggest that these IAP antagonists may promote cell death through mechanisms that do not involve antagonism of DIAP1本身。因此，我们正在积极追求这些替代的死亡途径。
TRAIL-induced apoptosis and resistance in prostate cancer: Tumor cells are normally removed from the body, in part, through the activation ofdeath receptors位于肿瘤细胞上，例如FAS/CD95或死亡受体-4和5（DR4/5）。这些受体通过其同源配体，FASL和肿瘤坏死因子相关凋亡诱导的配体（TRAIL）激活，并且由于其在癌细胞中选择性诱导凋亡的能力，因此具有潜在的治疗价值。实际上，目前正在针对各种癌症治疗DR4/5的重组步道和对DR4/5的激动抗体。不幸的是，约有50％的肿瘤表现出对步道的抵抗力。我们正在使用两者都研究前列腺癌中抗性的主要机制体外and animal models.
教育与培训
德克萨斯大学奥斯汀分校博士，1999年
Research Info
Apoptosis and Autophagy