GRK 2098: Biomedicine of the acid sphingomyelinase/acid ceramidase system

过去的25年彻底改变了我们对鞘脂的看法，以前我们认为鞘脂主要是细胞膜的结构元素。我们现在知道，鞘脂是许多基本细胞过程的中心。最近的努力将这些见解转化为临床应用，用于治疗多发性硬化症、癌症、囊性纤维化、肺炎、严重抑郁症、神经退行性疾病或黄斑变性。RTG旨在为新兴的鞘脂生物医学领域的博士、医学博士/博士、医学博士和高中生提供培训。本论文主要针对酸性鞘氨酸酶(ASM)/神经酰胺/酸性神经酰胺酶(Ac)/鞘氨醇/鞘氨醇激酶(SPK)/1-磷酸鞘氨醇(S1P)通路进行研究，并将探讨该通路在炎症性肠病和Graves眼眶病等炎症性疾病中的意义；在感染性疾病中的意义；在全身和肺部分枝杆菌感染和铜绿假单胞菌感染中的意义；在囊性纤维化中的意义；在癌症中，尤其是在抵抗辐射和成功治疗恶性肿瘤中的作用；以及在心血管疾病中的意义，包括动脉硬化、缺血性梗塞和动脉瘤形成。所有项目都通过临床前项目将基础科学转化为临床应用。为了实现我们的目标，我们制定了11个真正具有协同作用的项目，这些项目将由埃森和纽约的合作伙伴共同实施。因此，学生将能够在两个小组中进行自己的项目工作。从定期研讨会和演讲，到务虚会、暑期学校和会议，过多的教学内容将为两个伙伴国家的博士生提供极好的培训机会。

The past 25 years have completely changed our view of sphingolipids, which were previously considered to be primarily structural elements of cellular membranes. We now know that sphingolipids are central to many fundamental cellular processes. Very recent efforts translated these insights into clinical applications directed at treating, for example, multiple sclerosis, cancer, cystic fibrosis, pneumonia, major depression, neuro-degenerative diseases, or macular degeneration. The RTG aims to provide training for PhD, MD/PhD, MD, and high school students in the emerging field of the biomedicine of sphingolipids. The proposed dissertation projects focus strictly on the acid sphingomyelinase (Asm)/ceramide/acid ceramidase (Ac)/sphingosine/sphingosine kinase (SPK)/sphingosine 1-phosphate (S1P) pathway and will investigate the significance of this pathway in inflammatory disorders such as inflammatory bowel disease and Graves' Orbitopathy; in infectious diseases, for example in systemic and pulmonary mycobacterial and P. aeruginosa infection; in cystic fibrosis; in cancer, in particular in the role of this pathway in both resistance to radiation and successful treatment of malignancy; and in cardiovascular disease, including arteriosclerosis, ischemic infarct, and aneurysm formation. All projects translate basic science through pre-clinical projects into clinical applications. To achieve our goals, we have developed 11 truly synergistic projects that will be conducted by partners working together in Essen and New York. Thus, students will be able to work on their own projects in both groups. A plethora of teaching elements, ranging from regular seminars and presentations, to retreats, summer schools, and conferences, will provide doctoral students with excellent training opportunities in both partner countries.