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Samuel Pfaff

 

Samuel Pfaff

Samuel Pfaff

Professor and Helen McLoraine Developmental Chair in Neurobiology
Gene Expression Laboratory

"Our brains are composed of neuronal circuits with an estimated 100 trillion connections. My lab is interested in unmasking the strategies that nature has devised to generate this immense diversity of cells and complexity of connections by focusing on the way that the spinal cord is assembled during fetal development. We expect this information to provide novel insight into how we can harness 'embryonic pathways' to repair or augment the central nervous system to treat birth defects, injuries, diseases, and aging."

Newly launched motor neurons—the nascent cells that emerge from the spinal cord and extend down the length of limbs such as arms, wings, and legs—must chart their course to distant destinations. The growing nerves are guided by the so-called growth cone, a structure at their bow, which is rich in the receptor molecules whose job is to receive cues from the environment, much as ancient mariners who observed the stars and set their course accordingly.

During development, the growth cone continuously pushes forward, while the lengthening neuron behind it matures into the part of the cell called the axon. Once the growing cell "lands" at its target in a muscle cell, it is the axon that will relay the messages that allow an animal to control and move its limbs at will.

A mutation Pfaff and his team christened Magellan, after the Portuguese mariner whose ship Victoria was first to circumnavigate the globe, recently led them to a key signal that helps growing motor neurons stay their course. In the mutants, growing neurons can be seen leaving the spinal cord normally but then appear to lose direction. Led astray by disordered growth cones, elongating cells develop "kinks" and sometimes fold back on themselves or become entwined in a spiral, forming coils outside the spinal cord.

The Magellan mutation is located in a gene known as Phr1, which is also active in other parts of the nervous system, indicating that it most likely functions to steer other types of neurons, such as those that enervate sensory organs or connect different regions of the brain. Studies of Magellan may therefore shed light on how a variety of neurological disorders might be treated with cell replacement strategies.

Understanding how motor neurons reach the appropriate targets is necessary for the implementation of novel therapies, including embryonic stem cell replacement for the treatment of current incurable disorders such as Lou Gehrig's disease, in which motor neurons undergo irreversible decay.

Lab Photo

Left to right:
Front row: Becky Hensley, Karen Lettieri, Matt Pankratz, Todd Macfarlan, Sam Pfaff, Will Alaynick, Ben Gallarda, Ge Bai, Xinwei Cao Back row: Ryan O'Leary, Dario Bonanomi, Laura Franco, Shane Andrews, Annie Chivatakarn, Tiffany Poon

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Samuel Pfaff

Faculty

Samuel Pfaff

Samuel Pfaff

Professor and Helen McLoraine Developmental Chair in Neurobiology
Gene Expression Laboratory

The main objective of Samuel Pfaff, a professor in the Gene Expression Laboratory, is to discover how nerve cells are formed and wire up correctly, focusing on the fetal development of the spinal cord.

Of special interest to him is how motor neurons develop and make connections between the spinal cord and muscles in the body, since these connections are necessary for all body movements. Spinal cord injuries lead to paralysis because motor neuron function is disrupted. Degenerative diseases such as ALS (Lou Gehrig's disease), spinal muscle atrophy and post-polio syndrome result from the loss of motor neurons.

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