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.
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.
Research assistant | Lab manager (Université Paris Cité)READ MORE
Master 1 StudentREAD MORE
Post-doc (Labex)READ MORE
Associate ProfessorREAD MORE
PhD student (DIM1HEALTH)
Master 2 StudentREAD MORE
PhD student (Université Paris Cité | FRM)
Master 2 StudentREAD MORE
Team Leader | ProfessorREAD MORE
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
Marie VILLARES – Postdoctoral fellow (EUR G.E.N.E) & former PhD student
Our research is supported by the following funding bodies :
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 : email@example.com
Aurélie finalist of the MT180 competition
Congratulations to Aurélie Richard, a PhD student in the team, for her participation in the Sorbonne Paris Cité Alliance final of "My thesis in 180 secondes". Aurélie Richard © Youtube Université Paris Cité We’re proud of you, Aurélie!À lire...
Congratulations to Aris and Angélique !
The graduation of the 2021 and 2022 classes of the European Master of Genetics took place last Saturday during the G.E.N.E symposium 2023.Among the graduates, we are proud to count two members of the team: Aristeidis, PhD and Angélique, AI & Lab manager ! From...
Welcome to Gabrielle
Gabrielle is our new M2 student.She will work on immune-related host genes dowregulated by Theileria parasites. Welcome in the team Gabrielle ! Read more
Welcome to Sara
Sara is our new M2 student.She will work on the Methylation of ESCRT-III proteins by SMYD3 and its funtion in cell division. Welcome in the team Sara ! Read more