Don W. Cleveland

Last updated

Don W. Cleveland
Cleveland Don.jpg
Cleveland in 2013
Born (1950-08-26) August 26, 1950 (age 73)
NationalityAmerican
Alma mater Princeton University (PhD)
New Mexico State University (BS)
Awards National Academy of Sciences, 2006
American Academy of Arts and Sciences, 2006
Institute of Medicine, 2012
Breakthrough Prize in Life Sciences, 2018
Scientific career
Fields Centromeres, aneuploidy and tumorigenesis
Mechanism and therapy in human neurodegenerative disease
Institutions Ludwig Cancer Research
University of California, San Diego
Johns Hopkins University
Doctoral advisor Marc W. Kirschner
Other academic advisors William Rutter

Don W. Cleveland (born 1950 in Waynesville, MO) is an American cancer biologist and neurobiologist.

Contents

Cleveland is currently the Department Chair of Cellular and Molecular Medicine [1] and Distinguished Professor of Medicine, Cellular and Molecular Medicine and Neurosciences [2] at the University of California at San Diego, and Head, Laboratory for Cell Biology at the San Diego branch of Ludwig Cancer Research. [3]

Biography

Cleveland grew up in Las Cruces, New Mexico. He earned a B.S. in physics in 1972 from New Mexico State University, and graduated as the valedictorian for the College of Arts and Sciences. [3]

Cleveland started graduate school at Princeton University in 1972, switching mid-year into biochemistry. He worked with Marc Kirschner and graduated with a Ph.D. in 1977. Cleveland's doctoral dissertation was titled "Purification and properties of tau, a microtubule associated protein which induces assembly of microtubules from purified tubulin". [4] As a graduate student, Cleveland provided the initial identification and characterization of tau, showing it to have characteristics of a natively unfolded protein. [5] Tau is now recognized to accumulate in Alzheimer's disease and to be the basis for chronic brain injury. [6] He also developed and published a peptide fingerprinting technique [7] that was so popular that it became a citation classic [8] Cleveland did postdoctoral work with William J. Rutter at the University of California at San Francisco from 1978 to 1981. Cleveland was the first to clone tubulin [9] [10] actin and keratin [11]

From 1981 through 1995, Cleveland was on the faculty of the Department of Biological Chemistry at the Johns Hopkins University School of Medicine. In 1995, he accepted a position at the San Diego Branch of Ludwig Cancer Research at the University of California at San Diego. Since 2008, he has been Chair of the Department of Cellular and Molecular Medicine.

Contributions to Science

Cleveland has made pioneering discoveries of the mechanisms of chromosome movement and cell-cycle control during normal cellular division, as well as of the principles of neuronal cell development and their relationship to the defects that contribute to inherited neurodegenerative disease. [12] Cleveland's research looks at the molecular genetics of axonal growth and motor neuron disease and the cell biology of mammalian chromosome movement. [13]

Most recently, his research has achieved a significant breakthrough in treating Huntington's disease, an inherited and degenerative brain disorder for which there is no cure. A one-time injection of a new DNA-based drug treatment - known as ASO (short for antisense oligonucleotide) - blocked the activity of the gene whose mutation causes the disease. A single treatment silenced the mutated gene responsible for the disease, slowing and partially reversing progression of the fatal neurodegenerative disorder in animal models. [14] This drug, called IONIS-HTTRx, was developed by scientists at Ionis Pharmaceuticals in collaboration with partners CHDI Foundation, Roche Pharmaceuticals and academic collaborators at University of California, San Diego and is now in a Phase 1/2a clinical study. [15]

Books

Cell and Molecular Biology of the Cytoskeleton: Molecular Mechanisms Controlling Tubulin Synthesis Edited by Jerry W. Shay (Plenum Press, 1986), ISBN   978-1-4612-9269-2

With Toni L. Williamson, Mouse Models in the Study of Genetic Neurological Disorders: Mouse Models of Amyotrophic Lateral Sclerosis Edited by Brian Popko (Kluwer Academic/Plenum Publishers, 1999), ISBN   0-306-45965-5

With Nicholas G. Theodorakis, Control of Messenger RNA Stability: Translationally Coupled Degradation of Tubulin mRNA Edited by Joel Belasco and George Brawerman (Academic Press, Inc., 1993) ISBN   0-12-084782-5

Select honors

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References

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  2. "Four Department of Medicine Faculty Members Are on 2015 Thomson Reuters Highly Cited Researchers List". News From The Department of Medicine. Regents of the University of California. Archived from the original on January 24, 2017. Retrieved February 2, 2016.
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  5. Mandelkow, E.-M.; Mandelkow, E. (March 20, 2012). "Biochemistry and Cell Biology of Tau Protein in Neurofibrillary Degeneration" (PDF). Cold Spring Harbor Perspectives in Medicine. 2 (7): a006247. doi:10.1101/cshperspect.a006247. PMC   3385935 . PMID   22762014.
  6. McKee; et al. (2009). "Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury". J Neuropathol Exp Neurol. 68 (7): 709–35. doi:10.1097/NEN.0b013e3181a9d503. PMC   2945234 . PMID   19535999.
  7. Cleveland, D.W.; Fischer, S.G.; Kirschner, M.W. & Laemmli, U.K. (1977). "Peptide mapping by limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis" (PDF). J. Biol. Chem. 252 (3): 1102–6. doi: 10.1016/S0021-9258(19)75212-0 . PMID   320200.
  8. Kresge, Nicole; Simoni, Robert D.; Hill, Robert L. (August 18, 2006). "The Development of Cleveland Peptide Mapping by Don W. Cleveland". The Journal of Biological Chemistry. 281 (33): e27. doi: 10.1016/S0021-9258(19)46364-3 .
  9. Janke, Carsten (August 18, 2014). "The tubulin code: Molecular components, readout mechanisms, and functions". The Journal of Cell Biology. 206 (4): 461–472. doi:10.1083/jcb.201406055. PMC   4137062 . PMID   25135932.
  10. Cleveland, Don W.; Lopata, Margaret A.; MacDonald, Raymond J.; Cowan, Nicholas J.; Rutter, William J.; Kirschner, Marc (May 1980). "Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes" (PDF). Cell. 20 (1): 95–105. doi:10.1016/0092-8674(80)90238-x. PMID   6893015. S2CID   54326866.
  11. Fuchs, Elaine V.; Coppock, Susan M.; Green, Howard; Cleveland, Don W. (November 1981). "Two distinct classes of keratin genes and their evolutionary significance" (PDF). Cell. 27 (1): 75–84. doi:10.1016/0092-8674(81)90362-7. PMID   6173133. S2CID   38166670.
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