Claire Eliane Le Pichon, Ph.D.
Unit on the Development of Neurodegeneration
We study the early pathophysiology of neurodegeneration in an effort to better understand the prodromal disease biology preceding neuronal death. Neurodegenerative diseases currently afflict over 7 million people in the United States alone. This number is projected to rise to 19 million by the year 2050. By the time neurodegenerative diseases are diagnosed, a large percentage of neurons has already been lost, thus in order to better treat these devastating illnesses we first need to elucidate the biology underlying disease initiation and progression. We address these questions using mouse models of neurodegeneration in which disease onset and progression is stereotyped and in which one can predict which neurons will degenerate and thus study their pre-symptomatic biology.
The launching point for our research centers around dual leucine zipper kinase or DLK which is a critical regulator of the neuronal stress response to injury. Although the DLK stress response has been more extensively studied in the context of acute physical injury such as nerve crush or transection, we have found that it also becomes activated in neurodegenerative disease (Le Pichon et al., 2017). DLK signaling directs a transcriptional program allowing the neuron to respond to the insult. For mammalian neurons of the central nervous system, DLK signaling more typically results in neurodegeneration, but in other contexts it can also promote regeneration. We are interested in better understanding (1) the mechanisms activating DLK signaling, (2) how and where this pathway fits in with other pathways of organelle-specific cellular stress, and (3) the factors influencing the final outcome for the cell, e.g. the ability to regenerate or degenerate. In a broader sense, this research will hopefully shed light on the questions of selective neuronal vulnerability in neurodegenerative disease, intercellular communication in disease pathogenesis, and disease progression and spreading.
Dr. Claire Le Pichon earned her B.A. degree from Cambridge University, U.K. and her Ph.D. in Biological Sciences from Columbia University in 2007 in the laboratory of Dr. Stuart Firestein, where her interest in neurodegenerative disease began while studying the function of the cellular prion protein PrPC. After her Ph.D., Dr. Le Pichon joined the Translational Neuroscience group at Genentech, where she worked on preclinical drug development for multiple neurodegenerative disease pipeline targets, using mouse models of disease. She was recruited as an Investigator to the NICHD in 2016. Her laboratory employs a multidisciplinary approach including mouse genetics, wide-scale imaging of whole brain tissue, next generation sequencing, and behavior to investigate the early events underlying the onset and progression of neurodegenerative disease.
This page was last updated on August 2nd, 2017