My laboratory studies how DNA is organised in the cell nucleus. The organisation of DNA is a critical part of the regulation of gene expression, by partitioning DNA into active regions, potentially active regions and inactive regions. This organisation is known as “epigenetic” regulation. We are particularly interested in the way DNA organisation is controlled by epigenetic regulatory proteins in stem cells and how this changes during embryonic development.
As one might expect, a key part of embryonic development is the precise control of cell proliferation. Many of the genes which regulate the balance between cell proliferation and differentiation in embryos are cancer genes when control of their activity is lost in adults. Furthermore, the epigenetic regulators are critical for regulation of growth and, not surprisingly, are commonly mutated in cancer.
We have studied the normal function of a class of these genes, known as “KATs” in particular KAT6A and KAT6B, which are mutated in aggressive forms of leukaemia. We have developed drugs against these proteins which are now in clinical trials with a view to developing a new class of anticancer drugs.
The Thomas lab has a long-term interest in understanding the epigenetic regulation of embryonic development and in particular has characterised the function of histone acetyltransferases. These chromatin modifiers are important regulators of development and deregulated in cancer.
More recently, Tim has completed a drug discovery project, developing acetyltransferase inhibitors and a new class of anti-cancer therapeutics.
The Thomas Laboratory collaborates closely with the Voss Laboratory.