Our goal is to understand the fundamental principles that control the specification and connectivity of spinal neurons involved in locomotion, particularly motor neurons. Over the long term these studies should provide insight into the basic principles involved in the proper formation of the nervous system, as well as provide practical information for treatments of spinal cord injury and diseases like amyotrophic lateral sclerosis, post polio syndrome, and spinal muscle atrophy. 

The approaches used in the lab include experiments with genetically modified mice, developmental studies with chicken embryos, and differentiation assays with ES cells. Currently the lab has three areas of investigation: the mechanisms that control gene regulation during neuronal fate specification, the analysis of axon guidance, and studies of the central pattern generator circuitry involved in locomotion.

 Education

• Undergraduate degree, Carleton College in Minnesota
• Ph.D., Molecular Biology, UC Berkeley
• Postdoctoral fellow, Vanderbilt University and the Center for Neurobiology at Columbia University

Awards and Honors

• Pew Scholar
• Basil O'Connor Award
• McKnight Scholar

Research:

Stem cells and fate specification

We are characterizing the molecular mechanisms that regulate how spinal cord neuronal types acquire their proper identity. We have used mouse genetics and in vivo studies with chick embryos to study the function of transcription factors, miRNAs, and cell polarity proteins. Increasingly, we have also begun to use mouse and human embryonic stem cells to characterize the molecular systems involved in regulating cell identity.

Axon Guidance

We are interested in understanding the signaling pathways that control motor neuron axon navigation. We have used genetic screens and in vitro assays to identify axon guidance molecules. More recently we have begun to rely on live cell imaging of growth cones to investigate the cell biology of axon growth.

Locomotor Circuitry

We are using mouse genetics to investigate the cellular and molecular underpinnings of the spinal cord central pattern generator. These experiments rely on electrophysiological recordings of evoked locomotor activity and optical methods for characterizing the embryonic formation of this circuitry.

Selected Publications

Song MR, Shirasaki R, Cai CL, Ruiz EC, Evans SM, Lee SK, Pfaff SL. T-Box transcription factor Tbx20 regulates a genetic program for cranial motor neuron cell body migration. Development. 2006 Dec;133(24):4945-55. [PDF]

Shirasaki R, Lewcock JW, Lettieri K, Pfaff SL. FGF as a target-derived chemoattractant for developing motor axons genetically programmed by the LIM code. Neuron. 2006 Jun 15;50(6):841-53. [PDF]

Marquardt T, Shirasaki R, Ghosh S, Andrews SE, Carter N, Hunter T, Pfaff SL. Coexpressed EphA receptors and ephrin-A ligands mediate opposing actions on growth cone navigation from distinct membrane domains. Cell. 2005 Apr 8;121(1):127-39. [PDF]

For a complete list of publications, please follow this link to PubMed.

Links

• Pfaff lab

Salk News Releases

• Salk Institute Scientist Receives $15.6 Million CIRM Disease Team Award to Develop Novel Stem-Cell Derived Therapy for Lou Gehrig's Disease, October 28, 2009
• Salk scientists selected as Howard Hughes Medical Institute investigators, May 27, 2008
• Sharing the road, April 10, 2008
• A mutation named Magellan steers nerve cells off course, November 21, 2007
• Salk neurobiologist receives Javits Neuroscience Investigator Award, August 24, 2007
• Detailed 3-D image catches a key regulator of neural stem cell differentiation in action, December 7, 2006
• New roles for growth factors: Enticing nerve cells to muscles, June 20, 2006
• In mice, walking (and running) depends on nerve cell chatter during development, April 13, 2005
• Molecular 'zipcode' guides nerves to correct places in body, April 7, 2005
• Motor Nerve Cell "Factory" Findings May Elicit Treatments for Spinal Cord Injury, Disease, June 4, 2003