CONTROL OF LEISHMANIA BY PROGRAMMED CELL DEATH (APOPTOSIS)

利什曼原虫引起人类疾病，有临床症状 从自我修复的皮肤损伤到致命的内脏 感染。此外，在流行地区，感染艾滋病毒的人 尤其容易感染利什曼原虫。对……缺乏了解 这种寄生虫的细胞生物学和致病机制完成了这项任务 控制这一严重的、全球性的健康风险是困难的。更接近 国内尤其令美国军事人员担忧，他们的 前往疫区或居住在疫区的家庭和其他旅行者。至 找到控制这种病原体的新方法，我们已经开始研究 为了了解细胞程序性死亡(细胞凋亡)的机制 利什马尼亚。我们已经证明了利什曼原虫细胞死亡是由 热休克或用抗利什曼药物治疗， Petastam与经典的细胞凋亡有一些相似之处 哺乳动物细胞。我们正在寻找更确凿的证据来证明 通过克隆利什曼原虫在这些寄生虫中的一种凋亡程序 已知的从线虫到人类保存的无融合基因的同源物。 下一步，我们计划操纵利什曼原虫中的凋亡基因，以改变 因此，利什曼原虫的细胞死亡途径可以被消除 容易被目前可用的药物取代，且毒副作用较小 通常与这些疗法相关的效果。

The Leishmania parasite causes human disease with clinical symptoms ranging from-self healing cutaneous lesions to a fatal visceral infection. Additionally, in endemic areas, people infected with HIV are especially prone to Leishmania infection. The lack of understanding of cell biology and pathogenic mechanisms of this parasite makes the task of controlling this grave, worldwide health risk difficult. Closer to home it is particularly of concern to U.S. military personnel, their families and other travelers visiting or living in the endemic areas. To find novel methods for control of this pathogen, we have initiated study to understand the mechanism of programmed cell death (apoptosis) in Leishmania. We have demonstrated that Leishmania cell death induced by heat shock or treatment with one of the anti-leishmanial drugs, pentastam, bears some similarities to classical apoptosis seen in mammalian cells. We are seeking more definitive evidence of the existence of an apoptotic program in these parasites by cloning Leishmanial homolgues of known apototic genes conserved from nematodes to humans. Next , we plan to manipulate apoptotic genes in Leishmania so as to alter the cell death pathway in Leishmania parasite thus can be eliminated with ease by the currently available drugs and has less toxic side effects commonly associated with these therapies.