Weitzman group
Plasticity of Cellular Phenotypes
Key words : lysine methylation, cancer, host-parasite interactions, drug targeting
Team Plasticity of Cellular Phenotypes
This picture was taken during the 2021 Unit retreat.
From left to right : Aurélie, Marie, Jérémy, Jonathan, Souhila, Aristeidis, Angélique
© Fabrice Ferron
We are interested in cellular identities and the molecular mechanisms that underlie different cellular states. Cell signaling pathways converge on post–translational modifications (PTMs) which play critical roles in regulating chromatin structure and gene expression. Our team focuses on protein methylation as a key event that links signaling pathways to cellular phenotypes. We are interested in understanding the role of Lysine methylation, of both histone and non-histone substrates, in different cellular scenarios.
In the team, we work on two research axes :
PIN-ning down Host-Parasite interactions
We are interested in how infectious agents develop intricate mechanisms to hijack the genetic and epigenetic machinery of their host cells to change phenotypic states. We developed a research program to investigate how the intracellular parasite Theileria annulata hijacks host signaling pathways to maintain cell transformation. Theileria is the only parasite known to transform it’s host cells into tumor-like cells. We want to understand how it does this and how we can stop it.
SET-ting the scene with SMYD enzymes in cancer
The methylation of lysine residues is a key post-translational modification (PTM) which has been studied primarily in the context of histone methylation and epigenetic regulation of gene expression. Beyond this well-established role, lysine methylation is now emerging as a regulator of non-histone protein-protein interactions and protein function. Our laboratory investigates the role of lysine methyltransferase enzymes (particularly SMYD family members) and how lysine methylation contributes to deregulated cellular processes and to the development of cancer.
Publications
Selected recent publications
- Trifloxystrobin Blocks the Growth of Theileria Parasites and Is a Promising Drug to Treat Buparvaquone Resistance. Communications Biology. 2022 Nov
Villares M, Lourenço N, Berthelet J, Lamotte S, Regad L, Medjkane S, Prina E, Rodrigues-Lima F, Späth GF, WEITZMAN JB. - Dynamic methylation of histone H3K18 in differentiating Theileria parasites. Nature Com. 2021 May 28
Cheeseman K, Jannot G, Lourenço N, Villares M, Berthelet J, Calegari-Silva T, Hamroune J, Letourneur F, Rodrigues-Lima F, Weitzman JB. - The clever strategies used by intracellular parasites to hijack host gene expression. Semin Immunopathol. 2020 Apr
Villares M, Berthelet J, Weitzman JB. - Intracellular Theileria Parasites PIN Down Host Metabolism. Front Cell Dev Biol. 2020 Mar
Medjkane S, Weitzman JB. - Cell geometry and the cytoskeleton impact the nucleo-cytoplasmic localisation of the SMYD3 methyltransferase. Sci Rep. 2020 Nov
Pereira D, Richert A, Medjkane S, Hénon S, Weitzman JB. - The SMYD3 methyltransferase promotes myogenesis by activating the myogenin regulatory network. Sci Rep. 2019 Nov 21
Codato R, Perichon M, Divol A, Fung E, Sotiropoulos A, Bigot A, Weitzman JB, Medjkane S. - Secreted parasite Pin1 isomerase stabilizes host PKM2 to reprogram host cell metabolism. Commun Biol. 2019 Apr 30
Marsolier J, Perichon M, Weitzman JB, Medjkane S. - Mutations in the TaPIN1 peptidyl prolyl isomerase gene in Theileria annulata parasites isolated in Sudan. Int J Parasitol Drugs Drug Resist. 2019 Dec
Salim B, Chatanga E, Jannot G, Mossaad E, Nakao R, Weitzman JB. - Host Parasite interactions : an intimate epigenetic relationship. Cell Microbiol. 2015 Aug
Cheeseman K, Weitzman JB. - Lost in post-translation. EMBO Rep. 2015 Jun
Putois O, Villa F, Weitzman JB. - Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation. Nature. 2015 Apr
Marsolier J, Perichon M, DeBarry JD, Villoutreix BO, Chluba J, Lopez T, Garrido C, Zhou XZ, Lu KP, Fritsch L, Ait-Si-Ali S, Mhadhbi M, Medjkane S, Weitzman JB. - What’s the damage? The impact of pathogens on pathways that maintain host genome integrity. Cell Host Microbe. 2014 Mar
Weitzman MD, Weitzman JB. - A reversible Warburg effect is induced by Theileria parasites to transform host leukocytes. Cell Cycle. 2013 Jul
Medjkane S, Weitzman JB. - Theileria induces oxidative stress and HIF1α activation that are essential for host leukocyte transformation. Oncogene. 2014 Apr
Medjkane S, Perichon M, Marsolier J, Dairou J, Weitzman JB. - OncomiR addiction is generated by a miR-155 feedback loop in Theileria-transformed leukocytes. PLoS Pathog. 2013
Marsolier J, Pineau S, Medjkane S, Perichon M, Yin Q, Flemington E, Weitzman MD, Weitzman JB. - The methylation landscape of tumour metastasis. Biol Cell. 2013 Feb
Cock-Rada A, Weitzman JB. - Role of the SMYD3 histone methyltransferase in tumorigenesis: local or global effects? Cell Cycle. 2012 May.
Medjkane S, Cock-Rada A, Weitzman JB. - SMYD3 promotes cancer invasion by epigenetic upregulation of the metalloproteinase MMP-9. Cancer Res. 2012 Feb
Cock-Rada AM, Medjkane S, Janski N, Yousfi N, Perichon M, Chaussepied M, Chluba J, Langsley G, Weitzman JB.
Members
Emmanuelle Ceddaha
PhD student - La Ligue Contre le Cancer
emmanuelle.ceddaha@etu.u-paris.fr
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Charles Frison-Roche
ATER (UFR SDV - Université Paris Cité)
charles.frisonroche@u-paris.fr
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Anciens membres
Shterna ASSOULINE – Master 1 Student
Teresa CALEGARI-SILVA – Visiting Post Doc
Kevin CHEESEMAN – Bioinformatics Platform Head – IR (CDD CNRS)
Alicia COCK-RADA – MD, PhD student
Roberta CODATO – PhD Fellow
Arnaud DIVOL – PhD Fellow
Maria Chiara GIRARDELLI – Master 2 Student
Guillaume JANNOT – Post Doctorant
Natacha JANSKI – Post-doctorant
Yulianna Julie KOZIY – Master 2 Student
Ivan KTORZA – Master 2 Student
Nelly LOURENçO – Engineer
Justine MARSOLIER – Former PhD Fellow & ATER
David PEREIRA – Post Doctoral Fellow
Martine PERICHON – AI Univ. de Paris / Lab Manager
Sandra PINEAU – PhD student
Gabrielle POLAK – Master 2 Student
Aurélie RICHARD – PhD student (Université Paris Cité | FRM)
Sara RONCARA – Master 2 Student
Marie VILLARES – Postdoctoral fellow (EUR G.E.N.E) & former PhD student
Funding
Our research is supported by the following funding bodies :
Contact
Jonathan Weitzman, PU
CNRS UMR7216 – Epigenetics and Cell Fate – Université Paris Cité
Lamarck B building, 3th floor, room 389
35, rue Hélène Brion, case 7042
75205 Paris Cedex 13
Email : jonathan.weitzman@u-paris.fr
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Theileria annulata and Cancer: a parasite strategy revealed!
Welcome to Emmanuelle !
Today, we welcome a new member to the team: Emmanuelle, a PhD student funded by the Ligue contre le Cancer.Emmanuelle will be working with Souhila to develop clinically applied tools based on our discovery of how methylation regulates cell division.Read more
Congratulations Dr. Aurélie Richard
Congratulations to Dr. Aurélie Richard, who spent four and a half years in the team during her second year of a master's degree and her PhD.Aurélie has worked very hard over all these years and deserves her new PhD title, earned after her thesis defense on November...
Welcome to the team !
Today we are welcoming three new members in the team. From left to right : Camille (PhD student), Marisol (PhD student) and Julia (engineer). Camille will work on the SMYD project while Marisol and Julia will work on the host-parasite interactions project. Read more