Claire Eliane Le Pichon, Ph.D.
Unit on the Development of Neurodegeneration
Over 100 million Americans are currently afflicted by a neurological disease. Some of these diseases can be fatal, and all are associated with morbidity and disability that affect the lives of patients as well as their caregivers. These diseases thus represent an increasingly large health burden on society. By the time most cases are recognized and diagnosed, a large percentage of affected neurons has already been lost. Therefore, a critical step towards developing new treatments is to better understand what happens during disease initiation and progression. This will enable earlier disease detection as well as potential interventions. Our work is dedicated to advancing our understanding of common molecular and cellular mechanisms of neurodegeneration, with the ultimate goal of developing treatments for neurodegenerative diseases and even preventing them. The lab uses the mouse and human iPSC–derived neurons as model systems.
One lab focus is on mechanisms of stress-response pathways in neurons, such as the evolutionarily conserved axon-damage signaling pathway under the control of DLK (dual leucine zipper kinase; MAP3K12). This kinase is a critical regulator of the neuronal stress response to axon 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 plays an important role in mouse models of neurodegenerative disease (Le Pichon et al., 2017). We are interested in better understanding the mechanisms activating DLK signaling, how this pathway intersects with other pathways of cellular stress, and factors downstream of DLK signaling that influence the final outcome for the cell, for example neuronal death versus survival or regeneration. Another central theme in the lab is to understand fundamental differences between vulnerable and resilient populations of neurons in models of acute traumatic injury and in chronic disease.
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 PhD, Dr. Le Pichon joined the Translational Neuroscience group at Genentech, where she worked on preclinical drug development for neurodegenerative disease pipeline targets, using mouse models of disease. She was invited as an Investigator to the NICHD in 2016. Her laboratory employs a multidisciplinary approach including mouse genetics, wide-scale imaging of whole cleared tissues, single cell sequencing, and iPSC-derived neurons to investigate the early events underlying the onset and progression of neurodegenerative disease.
- Wlaschin JJ, Donahue C, Gluski J, Osborne JF, Ramos LM, Silberberg H, Le Pichon CE. Promoting regeneration while blocking cell death preserves motor neuron function in a model of ALS. Brain. 2023;146(5):2016-2028.
- Alkaslasi MR, Piccus ZE, Hareendran S, Silberberg H, Chen L, Zhang Y, Petros TJ, Le Pichon CE. Single nucleus RNA-sequencing defines unexpected diversity of cholinergic neuron types in the adult mouse spinal cord. Nat Commun. 2021;12(1):2471.
- Wlaschin JJ, Gluski JM, Nguyen E, Silberberg H, Thompson JH, Chesler AT, Le Pichon CE. Dual leucine zipper kinase is required for mechanical allodynia and microgliosis after nerve injury. Elife. 2018;7.
- Nguyen MQ, Le Pichon CE, Ryba N. Stereotyped transcriptomic transformation of somatosensory neurons in response to injury. Elife. 2019;8.
- Le Pichon CE, Meilandt WJ, Dominguez S, Solanoy H, Lin H, Ngu H, Gogineni A, Sengupta Ghosh A, Jiang Z, Lee SH, Maloney J, Gandham VD, Pozniak CD, Wang B, Lee S, Siu M, Patel S, Modrusan Z, Liu X, Rudhard Y, Baca M, Gustafson A, Kaminker J, Carano RAD, Huang EJ, Foreman O, Weimer R, Scearce-Levie K, Lewcock JW. Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease. Sci Transl Med. 2017;9(403).
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Genetics and Genomics
This page was last updated on Monday, November 7, 2022