Investigating the role of SOX9 in liver fibrosis

肝纤维化是一种破坏性的疤痕反应，由肝脏损伤(如酒精或感染)引起。疤痕会损害肝功能。肝纤维化的最终治疗方法是移植。不幸的是，由于需要移植的人数很多，这一数字有限。因此，在疾病的早期阶段找到有效的抗纤维化治疗将是非常有益的。要做到这一点，需要更好地了解疤痕是如何形成的。虽然在这方面已经取得了进展，但不幸的是，仍然没有得到批准的抗纤维化治疗。为了解决这个问题，我已经确定SOX9是负责调节疤痕形成的主要成分的核心因素。现在至关重要的是确定SOX9的丢失是否可以用作逆转瘢痕形成和最终肝纤维化的手段。该项目将开发模型来测试Sox9的缺失是否可以预防或改善肝纤维化，以及Sox9的过度表达是否会恶化或加速疾病。此外，我将发现SOX9下游还有哪些其他基因，并将这些基因与已知的肝纤维化重要信号通路相结合，以发现治疗肝纤维化的新靶点和潜力。总之，这些实验有望证明Sox9在器官纤维化中发挥重要作用，并帮助确定新的有价值的途径来寻找新的治疗方法。

Liver fibrosis is a devastating scarring reaction that results from injury to the liver (e.g. by alcohol or infection). The scarring impairs liver function. The ultimate treatment of liver fibrosis is transplantation. Unfortunately this is limited due to the high numbers of people in need of a transplant. For this reason, identifying effective anti-fibrotic treatments at early stages of disease would be hugely beneficial. To achieve this better understanding of how the scar forms is needed. Although progress has been made in this area, unfortunately there are still no approved anti fibrotic treatments. To tackle this problem, I have identified SOX9 as a core factor responsible for mediating large components of scar formation. It is now essential to determine whether loss of SOX9 can be used as a means of reversing scar formation and ultimately fibrosis in the liver. This project will develop models to test whether loss of Sox9 prevents or ameliorates liver fibrosis and if over-expression of Sox9 worsens or accelerates the disease. In addition, I will discover what other genes lie downstream of SOX9 and integrate these with known signalling pathways important in liver fibrosis to uncover new targets and potential for therapies against liver fibrosis.Taken together, these experiments are anticipated to prove an important role for Sox9 in organ fibrosis and assist in identifying new pathways of value in the search for new therapies.