New York — Ludwig Cancer Research extends its warmest congratulations to Don Cleveland, who has been a Member of the Ludwig Institute for Cancer Research since 1995 and today was awarded the prestigious Breakthrough Prize “for elucidating the molecular pathogenesis of a type of inherited amyotrophic lateral sclerosis (ALS), including the role of glia in neurodegeneration and for establishing antisense oligonucleotide therapy in animal models of ALS and Huntington’s disease.” The $3 million Breakthrough Prizes honor individuals for significant achievement in fundamental physics, mathematics and life sciences.
Cleveland’s contributions to the life sciences have been steady and spectacular. He and his colleagues discovered the tau protein, which is mutated or accumulates abnormally in cells, causing a range of cognitive disorders, including Alzheimer’s disease. Most notably, his lab also showed that a mutation in superoxide dismutase gives the enzyme a toxic activity that it otherwise would not have and that this toxicity drives the symptoms of a major genetic form of the neurodegenerative disease ALS. Cleveland has similarly made pioneering discoveries on the etiology of Huntington’s disease, and his work has broadly influenced approaches to treating a number of other neurodegenerative diseases.
His lab has also developed gene silencing technologies—designer DNA drugs—that have been adopted and put into clinical trials to treat ALS, Huntington’s disease and Alzheimer’s disease. The technology is currently being adapted for the treatment of Parkinson’s disease, chronic brain injury and glioblastoma, the most frequent cancer of the nervous system.
Cleveland has also long focused on the intricate mechanisms responsible for the correct parceling out of chromosomes to the daughters of a dividing cell—processes essential to the survival of cells as well as good health. He and his colleagues identified many of the genes that encode constituents of the protein cables or microtubules that draw chromosomes apart during cell division. They also described the components required to link those cables to chromosomes and align the chromosomes appropriately, identified the protein motor, CENP-E, that drives those processes and the molecular signaling cascades that prevent the misdistribution of chromosomes in dividing cells. Such errors are a defining trait of most advanced cancers. Cleveland’s discovery that suppressing CENP-E kills cancer cells led to the development of novel cancer therapies, two of which drug companies have taken into clinical trials.
Cleveland’s scientific insight and extraordinary creativity will continue to advance the world’s understanding of the cell’s most fundamental processes—and improve the prospects of patients diagnosed with cancer and devastating neurological diseases.
In addition to being a Member of the Ludwig Institute for Cancer Research, Don Cleveland is a Professor of Cellular and Molecular Medicine at the University of California, San Diego.