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 double or more 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 (DLK; MAP3K12) 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 plays an important role in mouse models of neurodegenerative disease (Le Pichon et al., 2017). DLK signaling directs a transcriptional program allowing the neuron to respond to injury. We are interested in better understanding (1) the mechanisms activating DLK signaling, (2) how and where this pathway interacts 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. 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 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.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Genetics and Genomics
This page was last updated on November 4th, 2018