What is the relative importance of MCL-1’s Anti-Apoptotic vs Apoptosis-Unrelated Functions in vivo?
Research seminar presented by:
Dr Kerstin Brinkmann
Victorian Cancer Agent Mid-Career-Research Fellow
WEHI
About Dr Kerstin Brinkmann
Kerstin is a Victorian Cancer Agent Mid-Career-Research fellow in the laboratory of Prof. Andreas Strasser at WEHI (Melbourne, Australia). Kerstin has been trained in biochemistry, genetics and pharmacology at CECAD (Cologne, Germany) and joined WEHI in 2015. Kerstin is an emerging leader in the field of cell death as evidenced by 22 publications including 5 first author publications in leading journals such as EMBO J, Cell Death and Differentiation and Cell Reports. Her research focuses on the improvement of cancer therapy by evaluating potential treatment side effects (e.g. damage to healthy tissue) of different chemotherapeutic treatment protocols, including DNA damaging chemotherapy and BH3 mimetic compounds. Kerstin currently leads a small team of 2 PhD students and 1 research assistant and holds funding for her independent research program from the Victorian Cancer Agency and the NHMRC (as CIA) and the Cancer Council Victoria (as CIB).
Abstract
MCL1 is amplified in >10% of human cancers. MCL-1-inhibitors are amongst the most promising new cancer therapeutics, however, concerning on-target side effects were observed in early clinical trials. To allow the safe clinical application of MCL-1-inhibitors, a profound understanding of all functions of MCL-1 is required. Amongst the pro-survival BCL-2 family members, MCL-1 is unique in being essential for early embryogenesis and the survival of many cell types (malignant and non-malignant) that are not impacted by the loss of any other pro-survival BCL-2 protein. Apoptosis-unrelated functions of MCL-1 in cellular metabolism might underlie this unique requirement, but their in vivo relevance is unknown. To determine the importance of anti-apoptotic compared to apoptosis-unrelated functions of MCL-1, we generated “pro-survival gene-swap” mice. We hypothesized that BCL-XL, BCL-2 and A1 can substitute MCL-1’s anti-apoptotic role but not its alleged apoptosis-unrelated function(s). The exciting results of these studies will be discussed during this seminar.
Public Health
