David Raizen
Assistant Professor, Dept of Neurology

Genetics and Gene Regulation Program

Address

1400 TRL
125 S. 31st Street
Philadelphia PA 19104

Office tel.: 215-746-4809
Lab tel.: 215-746-3039
Fax: 215-746-4814
E-mail: raizen@mail.med.upenn.edu


Education

University of Texas at Austin, B.A. (Biochemistry), 1989.

University of Texas Southwestern Medical School, PhD (Neuroscience), 1997.

University of Texas Southwestern Medical School, MD (Medicine), 1997.

Research Interests

• The regulation and purpose of sleep-like behavior in C. elegans

Key words: C. elegans, sleep, synaptic plasticity, behavioral genetics, quiescence, cGMP, locomotion

Description of Research

Despite the fact that we spend one third of our life sleeping, and despite the fact that all animals appear to sleep, the purpose or sleep remains a mystery. In addition, the molecular basis underlying sleep/wake regulation is poorly understood.

My lab uses C. elegans as a model system to answer 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 reversibility, increased sensory arousal threshold, and homeostasis, which is manifested by a decreased latency to sleep and an increased depth of sleep following a period of deprivation. We have identified a novel regulator of sleep like behavior in worms. This gene, called egl-4, encodes a cGMP dependent protein kinase. We are studying how egl-4 acts to promote this worm sleep-like state.

By studying the purpose and genetic regulation of C. elegans lethargus, we hope to identify additional novel sleep regulators, and to gain insight into the function of sleep, a central biological mystery.

Selected Publications

You Yj, Kim J, Raizen DM,and Avery L. Insulin, cGMP, and TGF-b Signals Regulate Food Intake and Quiescence in C. elegans: A Model for Satiety Cell Metabolism, 2008 in press.

Raizen DM, Zimmerman JE, Maycock MH, Ta UD, You YJ, Sundaram MV, Pack AI., Lethargus is a Caenorhabditis elegans sleep-like state. Nature. 2008 Jan 31;451(7178):569-72.

Raizen DM, Mason TB, Pack AI. Genetic basis for sleep regulation and sleep disorders. Semin Neurol. 2006 Nov;26(5):467-83. Review.

Zimmerman JE, Rizzo W, Shockley KR, Raizen DM, Naidoo N, Mackiewicz M, Churchill GA, Pack AI. Multiple mechanisms limit the duration of wakefulness in Drosophila brain. Physiol Genomics. 2006 Nov 27;27(3):337-50.

Raizen DM, Cullison KM, Pack AI, Sundaram MV.A novel gain-of-function mutant of the cyclic GMP-dependent protein kinase egl-4 affects multiple physiological processes in Caenorhabditis elegans. Genetics. 2006 May;173(1):177-87.

Search PubMed for more articles

Lab

Rotation Projects

1. Sleep regulation projects including the role of cAMP and cGMP signaling in sleep regulation.
2. Sleep purpose projects including the relationship between synaptic plasticity, metabolic cycles and sleep
3. Project focused on assessing effects of sleep-active drugs on worm behavior.

Lab personnel:

Uyen Ta, Technician
Wendy Rizzo, Medical Student
Annesia Lamb, Technician