Don W. Cleveland

Don W. Cleveland is Professor and Department Chair of Cellular and Molecular Medicine at the University of California, San Diego in the VC-Health Sciences-Schools. His research spans two major areas: genome rearrangement in cancer and mechanisms/therapies for neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS).

Research Focus

Dr. Cleveland's laboratory investigates:

• Genome rearrangement in cancer, particularly chromosomal instability, aneuploidy, and complex chromosome rearrangements like chromothripsis
• Mechanisms of neurodegeneration in amyotrophic lateral sclerosis (ALS) and related disorders
• TDP-43 proteinopathies and their role in ALS and frontotemporal dementia
• Mitotic spindle assembly and chromosome segregation mechanisms
• Development of therapeutic approaches for neurodegenerative diseases, including antisense oligonucleotide therapies

Research Trends

Analysis of Dr. Cleveland's recent publications reveals a strong focus on TDP-43-related mechanisms in neurodegenerative diseases, particularly ALS. His work has identified how loss of stathmin-2 due to TDP-43 dysfunction leads to motor neuron degeneration, and how this pathway can be targeted therapeutically. In cancer research, his laboratory has made significant contributions to understanding how chromosomal instability drives tumorigenesis through complex rearrangements. His work bridges basic molecular mechanisms with translational applications, as evidenced by the FDA approval of Qalsody (tofersen) for SOD1-ALS, which emerged from research in his laboratory.

Grants and Funding

Dr. Cleveland maintains continuous NIH funding with major grants including:

• TDP-43 acetylation, phase separation, aggregation, and clearance (R01NS121604)
• Determining stathmin-2 function and potential as a therapeutic target in ALS/FTD (R01NS112503)
• Mechanisms of chromosome segregation, aneuploidy, and tumorigenesis (R35GM122476)
• Disease mechanism in ALS and frontotemporal dementia (R01NS027036)

Laboratory and Collaborations

The Cleveland Lab at UCSD is a vibrant research group focused on both cancer biology and neurodegenerative disease mechanisms. The lab has made significant contributions to understanding TDP-43 proteinopathies in ALS and has been instrumental in developing antisense oligonucleotide therapies for neurodegenerative diseases. The lab maintains strong collaborations across UCSD and with other institutions, particularly in the areas of RNA biology, protein aggregation, and therapeutic development.