David M. Raizen, MD, PhD
Assistant Professor of Neurology
Department: Neurology
Graduate Group Affiliations
Contact information
Dept Neurology
462 Stemmler Hall
415 Curie Blvd
Philadelphia, PA 19104-4283
462 Stemmler Hall
415 Curie Blvd
Philadelphia, PA 19104-4283
Email:
raizen@mail.med.upenn.edu
raizen@mail.med.upenn.edu
Publications
Education:
BA (Biochemistry)
University of Texas at Austin, 1989.
MD (Medicine)
University of Texas Southwestern, 1997.
PhD (Neuroscience)
University of Texas Southwestern, 1997.
Permanent linkBA (Biochemistry)
University of Texas at Austin, 1989.
MD (Medicine)
University of Texas Southwestern, 1997.
PhD (Neuroscience)
University of Texas Southwestern, 1997.
Description of Research Expertise
Research InterestsThe regulation and function of sleep
Key Words: sleep, ecdysis, molting, behavior, amyloid, neuropeptides
Description of Research
Quiescent behavioral states are universal to the animal world with the most famous and mysterious of these being sleep. Despite the fact that we spend one third of our life sleeping, and despite the fact that all animals appear to sleep, the core function of sleep remains a mystery. In addition, the molecular basis underlying sleep/wake regulation is poorly understood.
We use C. elegans as a model system to address these questions. C. elegans offers many experimental advantages including powerful genetic tools as well as a simple neuroanatomy.
Growth of C. elegans from an embryo to an adult is punctuated by four molts, during which the animal secretes a new cuticle and sheds its old one. Prior to each molt the worm has a quiescent behavioral state called lethargus. Lethargus has several similarities to sleep including rapid reversibility to strong stimulation, increased sensory arousal threshold, and homeostasis, which is manifested by an increased depth of sleep following a period of deprivation. Similarity to sleep at the molecular genetic level is demonstrated by the identification of signaling pathways that regulate C. elegans lethargus in the similar fashion to their regulation of sleep in mammals and arthropods. For examples, cAMP signaling promotes wakefulness and epidermal growth factor signaling promotes sleep in C. elegans and other organisms. We have identified new regulators of sleep like behavior in C. elegans and are currently studying how these regulators function to regulate sleep.
By studying the purpose and genetic regulation of nematode lethargus, we hope to identify additional novel sleep regulators, and to gain insight into why sleep and sleep-like states had evolved, a central biological mystery.
Rotation projects
Please see David about possible projects.
Selected Publications
Driver RJ, Lamb AL, Wyner AJ, and Raizen DM : DAF-16/FOXO Regulates Homeostasis of Essential Sleep-like Behavior during Larval Transitions in C. elegans. Current Biology 23(6): 501-506, March 2013.Belfer SJ,Chuang HS, Freedman BL, Yuan J, Norton M, Bau HH, and Raizen DM: Caenorhabditis-in-Drop array for monitoring C. elegans quiescent behavior. Sleep in press, 2013.
Dabbish NS, Raizen DM.: GABAergic synaptic plasticity during a developmentally regulated sleep-like state in C. elegans. Journal of Neuroscience 31(44): 15932-15943, Nov 2011.
Chuang HS, Raizen DM, Lamb A, Dabbish N, Bau HH.: Dielectrophoresis of Caenorhabditis elegans. Lab on Chip 11(4): 599-604, Feb 2011.
Zimmerman JE, Raizen DM, Maycock MH, Maislin G, Pack AI.: A video method to study Drosophila sleep. Sleep 31(11): 1587-1598, November 2008.
David M. Raizen, John E. Zimmerman, Matthew H. Maycock, Uyen D. Ta, Young-jai You, Meera V. Sundaram & Allan I. Pack: Lethargus is a Caenorhabditis elegans sleep-like state. Nature 451, January 2008.
You, Y., Kim, J., Raizen, D. M., and Avery, L.: Insulin, cGMP and TGF-ß signals regulate food intake and quiescence in C. elegans: a model for satiety Cell Metabolism 7: 249-257, 2008.
Zimmerman, J. E., Raizen, D. M., Shockley, K., Churchill, G. A., and Pack, A. I.: Temporal changes in gene expression with sleep and wake in the Drosophila brain. Physiological Genomics 27(3): 337-350, September 2006.
Raizen, D. M., Cullison, K. M., Pack, A. I, and Sundaram, M. V.: A novel gain-of-function mutant of the cGMP-dependent protein kinase egl-4 affects multiple physiological processes in C. elegans. Genetics 173(1): 177-187, May 2006.
Raizen, D. M., Brooks-Kayal, A., Steinkrauss, L., Tennekoon, G. I., Stanley, C. A., and Kelly, A.: Central nervous system hyperexcitability associated with glutamate dehydrogenasae gain of function mutations. Journal of Pediatrics 146(3): 388-394, March 2005.