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Guilherme Nader, PhD
Assistant Professor
Dr. Nader is an assistant professor in the Department of Pathology and Laboratory Medicine at CHOP. His research topics are focused on the nuclear mechano-sensing of cells that grow and move within dense microenvironments such as tumor microenvironment, interstitial space, or densely packed tissue.
Bio
Dr. Guilherme Nader investigates cellular mechanisms underlying different migratory strategies, with focus on cytoskeleton and cytoskeleton-associated motors, adhesion receptors/focal adhesions, endocytic trafficking, and nuclear mechanotransduction.
During his postdoctoral research at Institut Curie in Paris, Dr. Nader adopted a variety of microfabricated tools and different 3D assays to more closely recapitulate in vivo microenvironments. He found that the nucleus ruptures when cells experience physical confinement when migrating or growing within tight spaces. Dr. Nader observed that repeated nuclear envelope rupture led to chronic DNA damage and caused healthy cells to become senescent while malignant cells became more invasive. He identified TREX1 as the exonuclease responsible for DNA damage following nuclear rupture. He showed that TREX1 depletion prevented tumor progression in a mouse model of breast cancer.
After completing his postdoctoral studies, Dr. Nader started his own lab in the Department of Pathology and Laboratory Medicine of Children’s Hospital of Philadelphia Research Institute. His research focuses on nuclear mechanosensing in cells that grow and move within dense microenvironments, constantly imposing physical stresses that impact cell behavior, function, and fate.
Education and Training
BS, University of Sao Paulo (Biology), 2006
MS, University of Sao Paulo (Molecular and Cellular Biology), 2009
PhD, Columbia University (Cell Biology), 2015
Postdoctoral Research Fellowship, Institut Curie, 2016-2022
Titles and Academic Titles
Assistant Professor
Professional Awards
Fellowship for Masters Student Research (FAPESP),Brazil, 2007-2009
ASCB Travel Award, 2012, 2013, 2019
Grandes Avancées Françaises en Biologie 2022, Institut de France-Académie des sciences, 2022
Publication Highlights
PubMed:
Nader GPF, Williart A, Piel M. Nuclear deformations, from signaling to perturbation and damage. Curr Opin Cell Biol. 2021 Oct; 72: 137-145. PMID: 34461580
Nader GPF, Agüera-Gonzalez S, Routet F, Gratia M, Maurin M, Cancila V, Cadart C, Palamidessi A, Ramos RN, San Roman M, Gentili M, Yamada A, Williart A, Lodillinsky C, Lagoutte E, Villard C, Viovy JL, Tripodo C, Galon J, Scita G, Manel N, Chavrier P, Piel M. Compromised nuclear envelope integrity drives TREX1-dependent DNA damage and tumor cell invasion. Cell. 2021 Sep; 184(20): 5230-5246.e22. PMID: 34551315
Lomakin AJ, Cattin CJ, Cuvelier D, Alraies Z, Molina M, Nader GPF, Srivastava N, Sáez PJ, Garcia-Arcos, JM, Zhitnyak IY, Bhargava A, Driscoll MK, Welf ES, Fiolka R, Petrie RJ, De Silva NS, González-Granado J M, Manel N, Lennon-Duménil AM, Müller DJ, Piel, M. The nucleus acts as a ruler tailoring cell responses to spatial constraints. Science. 2020 Oct; 370(6514): eaba2894. PMID: 33060332
Gentili M, Lahaye X, Nadalin F, Nader GPF, Puig Lombardi E, Herve S, De Silva NS, Rookhuizen DC, Zueva E, Goudot C, Maurin M, Bochnakian A, Amigorena S, Piel M, Fachinetti D, Londono-Vallejo A, Manel N. The N-terminal domain of cGAS determines preferential association with centromeric DNA and innate immune activation in the nucleus. Cell Rep. 2019 Feb; 26(9): 2377-2393.e13. PMID: 30811988
Nader GPF, Ezratty EJ, Gundersen GG. FAK, talin and PIPKIγ regulate endocytosed integrin conformation to polarize focal adhesion assembly. Nat Cell Biol. 2016 May; 18(5)491-503. PMID: 27043085