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. We model neurodegeneration in mice to elucidate disease biology preceding neuronal death within the context of a whole organism. We have a particular interest in stress response pathways that are activated in neurons during the course of disease. We also study these pathways in human iPSC-derived neurons.
The launching point for our research centers around dual leucine zipper kinase (DLK; MAP3K12), 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 (1) the mechanisms activating DLK signaling, (2) how and where this pathway intersects with other pathways of cellular stress, and (3) factors downstream of DLK signaling that influence the final outcome for the cell, for example neuronal death versus survival or regeneration. In a broader sense, this research will hopefully lead to addressing questions such as 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 animal behavior to investigate the early events underlying the onset and progression of neurodegenerative disease.
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.
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).
Chesler AT, Szczot M, Bharucha-Goebel D, Čeko M, Donkervoort S, Laubacher C, Hayes LH, Alter K, Zampieri C, Stanley C, Innes AM, Mah JK, Grosmann CM, Bradley N, Nguyen D, Foley AR, Le Pichon CE, Bönnemann CG. The Role of PIEZO2 in Human Mechanosensation. N Engl J Med. 2016;375(14):1355-1364.
Ghitani N, Barik A, Szczot M, Thompson JH, Li C, Le Pichon CE, Krashes MJ, Chesler AT. Specialized Mechanosensory Nociceptors Mediating Rapid Responses to Hair Pull. Neuron. 2017;95(4):944-954.e4.
Lee SH, Le Pichon CE, Adolfsson O, Gafner V, Pihlgren M, Lin H, Solanoy H, Brendza R, Ngu H, Foreman O, Chan R, Ernst JA, DiCara D, Hotzel I, Srinivasan K, Hansen DV, Atwal J, Lu Y, Bumbaca D, Pfeifer A, Watts RJ, Muhs A, Scearce-Levie K, Ayalon G. Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement. Cell Rep. 2016;16(6):1690-1700.
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Genetics and Genomics
This page was last updated on November 15th, 2019