Gabriella Esposito
Molecular basis and pathogenesis of inherited and acquired genetic diseases

Gabriella Esposito


1988 Master degree in Biological Sciences

1996 Residency in General Pathology

1996 PhD in Biochemistry

2003 Research Assistant in Biochemistry (BIO/10), Faculty of Medicine, University of Naples Federico II

2005 Associate Professor of Clinical Biochemistry and Clinical Molecular Biology (BIO/12)


In 1990, as a fellow of the National Research Council, she started to study the molecular basis of inherited diseases, i.e. haemophilia and hereditary fructose intolerance (HFI). Her PhD thesis project was focused on the characterization of the mutations leading to thalassemia in Italy. In 1997, she started her post-doctoral fellow at the laboratory of Prof. Francesco Salvatore, where she carried out the first experiments for expression, purification and functional study of aldolase B natural mutants associated with hereditary fructose intolerance (HFI).

Since 2001, she is group leader at CEINGE, where she leads researches and diagnostic activities for the study of molecular basis of inherited and acquired genetic diseases. She now lends her over twenty years of expertise to numerous diagnostic activities (including prenatal tests) mainly focused on the characterization, in affected patients and their relatives, of the molecular defects underlying neuromuscular, neurodegenerative and neurological disorders, isolated and syndromic eye diseases, isolated and syndromic hearing loss, tubulopathies, congenital ichthyoses, HFI, osteochondrodysplasias. Moreover, she studies the role of AF4 and its protein interactors in the molecular pathogenesis of the t(4;11) leukemia. This research line allowed discovering various AF4 protein interactors that are potential therapeutic targets. Lastly, as Health Director of Italian Health Service at the Integrated Care Department of Laboratory and Transfusion Medicine, AOU Federico II, she is the Responsible for the Departmental Program of Innovative Technologies in Laboratory Diagnostics of Genetic Diseases.


One of the researches that Gabriella Esposito carries out at CEINGE aims to study of the molecular basis of various inherited genetic diseases, i.e. neuromuscular and neurodegenerative diseases, inherited myopathies, congenital ichthyosis, isolate and syndromic eye diseases, isolated and syndromic hearing loss, hereditary fructose intolerance (HFI), Niemann-Pick disease type C and osteochondrodysplasias. Besides obtaining the molecular diagnosis, the identification of causative molecular alterations allows determining the molecular epidemiology of gene-specific sequence alterations in our population and to interpreter an increasing number of genomic variants according to the ACMG standards and guidelines. Molecular results are evaluated with respect to the genotype-phenotype correlation and familial segregation. Various bioinformatic and, in some cases, functional analysis can be used to assess the impact of naturally occurring sequence variants on gene expression.

Another research line aims to perform studies evaluating the impact of ALDOB sequence variants associated to HFI on the ALDOB enzyme structure, function and stability, by exploiting a eukaryotic (HEK293) knockout ALDOB-/- cellular model, obtained by genome editing. These cells recapitulate the disease phenotype because they do not survive when fructose, not glucose, is added in the culture medium.

This research line also has the goal to recover renal cells expressing ALDOB from urine of normal and HFI subjects. These cells can be used to test natural compounds that are putative inhibitors of the cellular pathways involved in fructose metabolism and to design a new non-invasive method for biochemical diagnosis of HFI. The last research line engages studying the role of AF4 and its protein interactors in the molecular pathogenesis of the mixed lineage leukemia, with the aim of identifying new molecular targets for the therapy of this untreatable form of blood cancer.

Research lines
  1. Molecular analysis of disease-related genes in patients affected by genetically heterogeneous neuromuscular and neurodegenerative diseases, inherited myopathies, congenital ichthyosis, isolate and syndromic eye diseases, isolated and syndromic hearing loss, tubulopathies and osteochondrodysplasias, by using a next-generation sequencing approach targeting a wide panel of genes listed in the OMIM database.
  2. Genotype-phenotype correlation study, identification of potential therapeutic molecules and development of a new non-invasive test for biochemical diagnosis of hereditary fructose intolerance (HFI) by using an ALDOB-/- cellular model that phenocopies the disease when fructose is supplemented to the culture medium (Figure 1)
  3. Analysis of the role of key proteins involved in the molecular pathogenesis of t(4;11) acute leukemia. We previously identified a set of proteins that contribute to the leukemic phenotype by interacting with AF4 and with the oncogenic chimera MLL-AF4 (Figure 2).
Research Group
  • Tiziana Fioretti, PhD
  • Adelaide Ambrosio, Biologist
Most relevant publications
  • Fioretti T, Cevenini A, Zanobio M, Raia M, Sarnataro D, Salvatore F, Esposito G. Crosstalk between 143-3q and AF4 enhances MLL-AF4 activity and promotes leukemia cell proliferation. Submitted
  • Esposito G, De Falco F, Neri I, Graziano C, Toschi B, Auricchio L, Gouveia C, Sousa AB, Salvatore F. Different TGM1 mutation spectra in Italian and Portuguese patients with autosomal recessive congenital ichthyosis: evidence of founder effects in Portugal. Br J Dermatol. 2013;168:1364-1367. doi: 10.1111/bjd.12179.  ISSN 0007-0963.
  • Esposito G, De Falco F, Tinto N, Testa F, Vitagliano L, Tandurella ICM, Iannone L, Rossi S, Rinaldi E, Simonelli F, Zagari A, Salvatore F. Comprehensive mutation analysis of the choroideremia gene reveals a missense variant that prevents binding of REP1 with Rab geranylgeranyl transferase. Hum Mutat 2011, 32:1460-9, doi: 10.1002/humu.21591. ISSN 1059-7794
  • Esposito G, Cevenini A, Cuomo A, De Falco F, Sabbatino D, Pane F, Ruoppolo M, Salvatore F. Protein network study of human AF4 reveals its central role in the RNA Pol II-mediated transcription and in phosphorylation-dependent regulatory mechanisms. Biochem J. 2011, 438:121-31. ISSN 0264-6021
  • Esposito G, Imperato MR, Ieno L, Sorvillo R, Benigno V, Parenti G, Parini R, Vitagliano L, Zagari A, Salvatore F. Hereditary fructose intolerance: functional study of two novel ALDOB natural variants and characterization of a partial gene deletion. Hum Mutat. 2010, 31:1294-303 ISSN 1059-7794.