Chiara Lanzuolo - Researcher
Department and institution: CNR-Institute of Biomedical Technologies, Milan (ITB) and Istituto Nazionale di Genetica Molecolare “Romeo ed Enrica Invernizzi” INGM
tel. +39 02 00660 358
lab's website: Role of nuclear architecture in cell identity
see also: PubMed, Linkedin, Twitter (@ChiaraLanzuolo)
Keywords: Transcriptional regulation, chromatin conformation, Prostate and colorectal cancer, Emery Dreifuss Muscular Dystrophy, Laminopathies
Over the past 10 years a large number of mutations in the human lamin genes have been associated with numerous diseases collectively termed laminopathies. Although it is clear that structural organization and epigenetic regulation of chromatin are altered in diseases caused by mutant lamins, nothing is known about the specific functions of lamins in these processes under normal physiological conditions. The Polycomb group (PcG) of proteins is part of a conserved epigenetic cell memory system that prevents changes in cell lineage identity by maintaining transcription patterns through cell divisions via chromatin structure. We hypothesize an involvement of lamin in the coordination of gene expression regulating contemporary sub-set of genes throughout direct or indirect interactions with Polycomb epigenetic complexes. Our studies are focused on physiological processes such as differentiation and senescence and pathological conditions as premature senescence and lamin disorders to find the role Lamin A in the regulation of gene expression. To this aim we combine molecular and cellular biology, the use of high-resolution techniques, such as Chip, FISH, 4C and time-lapse microscopy supported by high performance computing for the analysis of data. The ultimate objective will be to produce the fundamental knowledge of functional interactions between Polycomb repressive complexes and Lamin A that could help to untangle the intricate cascade of events at the basis of lamin related diseases, providing new tools for preclinical studies.
Main topics of the group
In the last years innovative high-throughput-based genome conformational analysis combined with advanced imaging revealed that each chromosome is folded in a highly organized fashion and occupies specific territories in the nucleus, ensuring adequate regulation of gene expression and the maintenance of genome integrity. In recent years, what is emerging is that, besides the plasticity of the chromatin fundamental for fine-regulated process, the nuclear architecture can also influence important cellular processes and is a hallmark of the healthy cell. In several pathologies, the genome organization is often compromised in parallel to an aberrant nuclear morphology, which in some cases is used by cyto-pathologists in their official diagnosis as an indicator of malignancy. However, the hierarchical relationship between nuclear and genome reshaping and molecular mechanisms involved in both aberrant processes are still unknown. My group is devoted in understanding how the genome folding occur in the nuclear space finding the right orientation and nuclear position and how this conformation is then maintained or regulated in dynamic physiological processes in health and in disease. We started studying epigenetic factors known to play a key role in genome folding and function, the Polycomb group (PcG) of proteins. In our recent work we described for the first time a functional and evolutionary conserved crosstalk between the nuclear Lamin A/C and the PcG proteins, this being required for the maintenance of the PcG repressive functions. We are now committed in understanding the role of PcG/LaminA interplay in laminopathies, human disorders caused by mutations in Lamin A/C gene. Our studies are focused on physiological processes such as differentiation and senescence and pathological conditions as premature senescence and lamin disorders to find the role Lamin A in the regulation of gene expression. The ultimate objective will be to produce the fundamental knowledge of functional interactions between Polycomb repressive complexes and Lamin A that could help to untangle the intricate cascade of events at the basis of lamin related diseases, providing new tools for preclinical studies.
Current research projects
• Dissecting the role of nuclear architecture in genome organization and function
• Role of LaminA/C-Polycomb crosstalk in Emery Dreifuss Muscular Dystrophy
• Identification of epigenome alterations in Hutchinson-Gilford Progeria Syndrome
• Genome reshaping in prostate cancer progression
Internal and external collaborators
Dr Francesco Ferrari, IFOM, Italy
Dysfunctional polycomb transcriptional repression contributes to lamin A/C-dependent muscular dystrophy. J Clin Invest. 2020 May 1;130(5):2408-2421. doi: 10.1172/JCI128161.
Andrea Bianchi, Chiara Mozzetta, Gloria Pegoli, Federica Lucini, Sara Valsoni, Valentina Rosti, Cristiano Petrini, Alice Cortesi, Francesco Gregoretti, Laura Antonelli, Gennaro Oliva, Marco De Bardi, Roberto Rizzi, Beatrice Bodega, Diego Pasini, Francesco Ferrari, Claudia Bearzi, Chiara Lanzuolo
Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes. J Cell Biol. 2015 Nov 9;211(3):533-51. doi: 10.1083/jcb.201504035
Elisa Cesarini, Chiara Mozzetta, Fabrizia Marullo, Francesco Gregoretti, Annagiusi Gargiulo, Marta Columbaro, Alice Cortesi, Laura Antonelli, Simona Di Pelino, Stefano Squarzoni, Daniela Palacios, Alessio Zippo, Beatrice Bodega, Gennaro Oliva, Chiara Lanzuolo
Epigenetic alterations in muscular disorders. Comp Funct Genomics. 2012;2012:256892. doi: 10.1155/2012/256892
last update: June 2020