Epigenetic Control of Gene Expression in Leukaemia and Haematopoiesis

儿童急性淋巴细胞性白血病(ALL)过去是一种无法治疗的疾病。值得庆幸的是，对所有人的普遍护理有了很大改善，大约90%的儿童得到了治愈。不幸的是，ALL中仍有一些罕见的子集有复发的趋势，并且无法治疗。我们正试图了解这些罕见的、不可治愈的ALL的分子细节，以便设计新的治疗方法。为了做到这一点，我们研究了表观遗传学如何影响基因调控。基因是由DNA组成的，它们驻留在细胞核中，在那里它们充当细胞的硬件，需要被“读取”才能发挥作用。当基因被不适当地读取(或我们所说的“激活”)时，可能会导致癌症生长等异常行为。表观遗传学是不直接存储在DNA本身中的信息。例如，一些表观遗传信息存储在组蛋白携带的化学修饰中，组蛋白在一种名为染色质的结构中与DNA相互作用。越来越清楚的是，异常的表观遗传变化不仅在许多人类疾病中很常见，例如白血病，而且这些变化本质上是可逆的。我们的目标是帮助设计针对这些可逆表观遗传变化的疗法。

Acute lymphoblastic leukaemia (ALL) in children used to be a disease that was untreatable. Thankfully, general care for ALL has greatly improved so that ~90% of children are cured. Unfortunately, there are still rare subsets of ALL that have a tendency to relapse and are untreatable. We are trying to understand the molecular details of these rare, incurable ALLs in order to design new therapies. In order to do this, we study how epigenetics impacts gene regulation. Genes are made up DNA, and they reside in the nucleus, where they act as hardware for the cell that needs to be "read" in order to be functional. When genes are read (or what we call "activated")inappropriately, this can cause aberrant behaviour such as cancerous growth. Epigenetics is information that is not stored directly in the DNA itself. For example, some epigenetic information is stored in chemical modifications carried by histone proteins that interact with DNA in a structure called chromatin. It is becoming clear not only that aberrant epigenetic changes are common in many human diseases such as leukaemia, but that these changes by their very nature are reversible. Our goal is to help design therapies that can target these reversible epigenetic changes.