Prof. Elisa Giorgio
Mariia Zadorozhna: post-doc
Erica Bascetta: research fellow
Ludovica Fenaroli: undergraduate student
Cecilia Taccagni: undergraduate student
Anna Basile: undergraduate student
The lab is focused on the identification of rare genetic diseases (RGDs) associated with non-canonical mutations and on the development of therapeutic strategies for RGDs by RNA therapeutics and drug-repositioning approaches.
PROJECT 1. Illuminating the non-coding genome to improve diagnosis in RGDs. Next Generation Sequencing has enormously increased the capability to diagnose RGDs, however the majority of patients (about 60%) often lacks a definite diagnosis. The reasons for this gap are undoubtedly many, but a large portion of the missing heritability likely resides in non-coding and regulatory variants. The lab is aimed at identifying and characterizing RGDs associated with "position effects", namely mutations affecting regulatory elements such as enhancer and insulator and/or the 3D genome structure.
PROJECT 2. Innovative therapeutic strategies for RGDs. The lab is focused on innovative precision-medicine approaches to overcome the genetic defect underlying RGDs, as the mutated gene itself provides a potential druggable genomic target for therapeutic design. We are developing therapeutic options for i) a rare form of leukoencephalopathy, the adult-onset autosomal dominant leukodystrophy (ADLD) by RNA therapeutics (allele-specific RNAi) and drug repositioning approaches, ii) the Early Infantile Epileptic Encephalopathy type 9 by RNA therapeutics (silencing) and epigenetic editing (deadCas9-mediated epigenetic activation)
PROJECT 3. Identification of new disease-associated genes/new phenotype associated with known genes by genome and exome sequencing in subjects with neurodevelopment diseases, leukodystrophy, ataxias, complex syndromes, and fetal malformations. To this aim, the lab develops ad hoc functional assays aimed at corroborating the pathogenicity of the identified variants and at generating innovative and disease-relevant cellular models.
A HIGH-CONTENT DRUG SCREENING STRATEGY TO IDENTIFY PROTEIN LEVEL MODULATORS FOR GENETIC DISEASES: A PROOF-OF-PRINCIPLE IN AUTOSOMAL DOMINANT LEUKODYSTROPHY (ADLD). Elisa Giorgio et al., Hum Mutat. 2021 Jan;42(1):102-116. doi: 10.1002/humu.24147. Epub 2020 Dec 8. PMID: 33252173
ALLELE-SPECIFIC SILENCING AS TREATMENT FOR GENE DUPLICATION DISORDERS: A PROOF-OF-PRINCIPLE IN ADLD. Elisa Giorgio et al., Brain. 2019 Jul 1;142(7):1905-1920. doi: 10.1093/brain/awz139. PMID: 31143934
A NOVEL HOMOZYGOUS CHANGE OF CLCN2 (p. His590Pro) IS ASSOCIATED WITH A SUBCLINICAL FORM OF LEUKOENCEPHALOPATHY WITH ATAXIA (LKPAT). Elisa Giorgio et al., J Neurol Neurosurg Psychiatry. 2017 Oct;88(10):894-896. doi: 10.1136/jnnp-2016-315525. Epub 2017 May 4. PMID: 28473625
WHOLE EXOME SEQUENCING IS NECESSARY TO CLARIFY ID/DD CASES WITH de novo CNVS OF UNCERTAIN SIGNIFICANCE: TWO PROOF OF CONCEPT EXAMPLES. Elisa Giorgio et al., Am J Med Genet A. 2016 Jul;170(7):1772-9. doi: 10.1002/ajmg.a.37649. Epub 2016 Apr 25. PMID: 27108886.
A LARGE GENOMIC DELETION LEADS TO ENHANCER ADOPTION BY THE LAMIN B1 GENE: A SECOND PATH TO AUTOSOMAL DOMINANT LEUKODYSTROPHY (ADLD). Elisa Giorgio et al., Hum Mol Genet. 2015 Jun 1;24(11):3143-54. doi: 10.1093/hmg/ddv065. Epub 2015 Feb 20. PMID: 25701871; PMCID: PMC4424952.