Professor Jiri Neuzil
Our laboratory is interested, very generally, in cancer biology. More specifically, we study the role of mitochondria in cancer formation and progression, and the role of mitochondria as potential novel targets for anti-cancer therapy. Several years ago, we have identified mitochondrial complex II as a novel target for cancer therapy and designed several anti-cancer agents that act by destabilizing mitochondria by way of targeting complex II. We have defined ‘mitocans’ (an acronym derived from ‘mitochondria and cancer’), a group of small molecules with anticancer activity that act by destabilizing mitochondria; of the several classes of mitocans, we have been focusing on compounds that target mitochondrial respiratory complexes. Within this group of agents, we designed novel anti-cancer drugs by way of modifying them with the mitochondria-targeting vector, the triphenylphosphonium group that causes accumulation of the compounds at the interphase of the mitochondrial matrix and the inner mitochondrial membrane, adjacent to their molecular targets, respiratory complexes. Several of these agents are patent-protected, and one of them (mitochondrially targeted tamoxifen) is entering phase one clinical trial. Recently we have discovered (together with Prof. Michael Berridge from Wellington, New Zealand) horizontal transfer of mitochondria in mammals in vivo, and described this process in the context of the propensity of cancer cells to form tumours. This finding may be of more general nature, affecting various aspects of cell biology and pathology.
Broad Research Areas: Cancer cell biology; mitochondrial biology and respiration; anti-cancer therapy; mitochondrial targeting; horizontal transfer of mitochondria in health and disease