Combinatorial screens to identify novel targets to combat mitochondrial diseases.
Speaker: Eduardo Balsa-Martinez, PhD - Harvard Medical School - Dana-Farber Cancer Institute - Boston - MA - USA
Organizers: IRB Barcelona
Date: Tuesday, 19 March, 15:00h
Place: Felix Serratosa room
Host: Dr. Manuel Serrano, PhD - IRB Barcelona
Despite major advances in our understanding of the pathophysiology of mitochondrial diseases, we have no cures for these disorders. Therefore, there is an urgent unmet medical need to develop new technologies and platforms for identifying therapeutic opportunities to treat mitochondrial diseases. To address this need, I have employed a combination of chemical and CRISPR/Cas9 genome-editing screenings to identity novel genes and molecular targets that can be exploited therapeutically to treat mitochondrial disorders.Loss-of-function screens yielded BRD4 protein as a molecular target. BRD4 inhibition, either chemically or genetically, remodeled the mitochondrial proteome to increase the levels and activity of OXPHOS protein complexes, leading to rescue of the bioenergetic defects and cell death caused by inhibition of Complex I. Conversely, gain-of-function screens identified a previously uncharacterized link between electron transport chain functional and cellular redox homeostasis with relevant implications in neurodegenerative disorders associated with mitochondrial dysfunction.
Extraordinary Plenary Seminar