Division of Signal Transduction in Cancer and Metabolism
Dr. Aurelio Teleman
When cancer cells proliferate to form a tumor, they need to grow and to divide. Regulation of cell division (i.e. the cell cycle) has been extensively studied. In comparison, the mechanisms regulating cell growth (i.e. the accumulation of cell mass) are less well understood. The Teleman lab studies cell growth and its regulation.
For cells to grow, they need to produce biosynthetic building blocks such as nucleotides, amino acids and lipids. This occurs via regulation of the metabolic pathways that produce these molecules. Therefore, understanding cell growth requires understanding metabolism. Cells decide to grow, however, based on information coming from outside the cell, such as the presence of nutrients and growth factors. Cells receive and process this information via signaling pathways such as the insulin pathway. Therefore, understanding cell growth also requires understanding signaling pathways. Finally, the signaling pathways regulate the metabolic pathways, therefore the lab also studies the interface between signaling and metabolism.
Both the metabolic pathways, as well as the signaling pathways, are complex and intricate networks. These pathways, however, are conserved amongst animals. Therefore, the Teleman lab studies these pathways using a combination of human tissue culture together with the fruitfly Drosophila, since Drosophila is simplified and genetically tractable compared to mammals.
The aim of our work is to understand the processes regulating cell growth so that this knowledge can be used in the future for cancer therapy. Unlike other cells in the body, cancer cells have mutations that promote cell growth. Blocking this process will hopefully be a powerful method to specifically and efficiently inhibit tumor progression.
Senyilmaz D, Virtue S, Xu X, Tan CY, Griffin JL, Miller AK, Vidal-Puig A and Teleman AA. Regulation of mitochondrial morphology and function by Stearoylation of TfR1. (2015) Nature 525:124-8
Tiebe M, Lutz M, De La Garza A, Buechling T, Boutros M and Teleman AA. REPTOR and REPTOR-BP regulate organismal metabolism and transcription downstream of TORC1. (2015) Developmental Cell. 33:272-84
Schleich S, Strassburger K, Janiesch PC, Koledachkina T, Miller KK, Haneke K, Cheng Y-C, Kuechler K, Stoecklin G, Duncan KE and Teleman AA. DENR•MCT-1 Promotes Translation Reinitiation Downstream of uORFs to Control Tissue Growth. (2014) Nature 512: 208-212
Demetriades C, Doumpas N and Teleman AA. Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2. (2014) Cell 156:786-99