The DNA is the blueprint to build and operate each individual bacterium, plant, animal, and person. Decoding the information contained in the DNA requires a process called ‘transcription’. Transcription needs to happen at the right time and in the right place. Otherwise, humans can get diseases such as cancer, diabetes, and developmental abnormalities. But how are specific DNA programs transcribed to develop a functional organ, or to allow our body to adapt to a changing environment?
My lab studies ‘Mediator’, a molecular machine that is absolutely critical for transcription: without it, the information contained in DNA cannot be not properly read. Accordingly, Mediator genes are mutated or deregulated in many human diseases. But how exactly these Mediator mutations contribute to disease is not well understood.
We want to delineate how Mediator assures normal development, prevents disease, and promotes healthy aging. We use the worm Caenorhabditis elegans and the house mouse as animal models, because they share important aspects of human biology and because we can manipulate them with cutting-edge genetic methods. This way, we study how Mediator and its molecular partners regulate metabolism, help cells adapt to stress, control cell type specification and organ development, and prevent aging and age-associated decline. We anticipate that our work will lead to new entry points for therapies and drugs that can treat human diseases.
Canada Research Chair in Transcriptional Regulatory Networks (2009-2019)
- Jan A et al. eEF2K inhibition blocks Aβ42 neurotoxicity by promoting an NRF2 antioxidant response. Acta Neuropathologica, 133(1):101-119. PMID:27752775
- Grants et al. The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in Caenorhabditis elegans. Genetics, 202(2):583-99. PMID:26715664
- Ding et al. s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways. Cell Metabolism, 22(4):633-45. PMID:26321661
- Hou NS et al. Activation of the endoplasmic reticulum unfolded protein response by lipid disequilibrium without disturbed proteostasis in vivo. PNAS. 111(22):E2271-80. PMID:24843123
- Goh GYS et al. The conserved Mediator subunit MDT-15 is required for oxidative stress responses in C. elegans. Aging Cell, 13(1):70-79. PMID:23957350