The project of our research group aims at the identification of novel biomarkers for early prediction and progression of Parkinson's Disease  through a multidisciplinary approach integrating omics data and in vitro modelling.

Parkinson’s disease (PD) represents one of the most frequent neurodegenerative disorders whose socio-economic impact is enormous. PD is characterized by the loss of mesodiencephalic dopaminergic (mdDA) neurons of the substantia nigra pars compacta (SNpc). It has been demonstrated that disease’s symptoms occur in patients lacking 50-60% of their mdDA neurons, suggesting the need for early diagnosis of the disease and development of innovative therapeutic approaches.

The study takes advantage from the availability of a large collection of PD samples (about 800 PD patients including familiar and sporadic) recruited at IRCCS Neuromed for which we already collected and stored clinical information (neurological examination and drugs therapy), genetic data (WES) as well as DNA, serum, plasma and PBMC for the entire study cohort. Patients-derived fibroblast cell lines have been stored in our biobank and patient-derived induced pluripotent stem cells  (iPSC) are in progress.

Objectives

The project is focused at: i) the realization of diagnostic protocols for an early prediction of

Parkinson's disease; ii) studying the effect of the presence of specific variants or combinations of

variants on the severity and progression of the disease; iii) understanding whether and how genetic variants may influence identity and susceptibility to neurodegeneration of hiPSC-derived mdDA neurons carrying highly penetrant genetic combinations of variants in novel PD genes; iv) identifying novel biomarkers for PD through the integrated analysis of clinical, instrumental (PET, DaTScan) and omic data (exome, metabolome and transcriptome (scRNAseq)).

1. Gialluisi A, Reccia MG, Modugno N, Nutile T, Lombardi A, Di Giovannantonio LG, Pietracupa S,  Ruggiero D, Scala S, Gambardella S; International Parkinson’s Disease Genomics Consortium (IPDGC), Iacoviello L, Gianfrancesco F, Acampora D, D'Esposito M, Simeone A, Ciullo M, Esposito T. Identification of sixteen novel candidate genes for late onset Parkinson's disease. Mol Neurodegener. 2021 Jun 21;16(1):35. doi: 10.1186/s13024-021-00455-2.
2. König E, Nicoletti A, Pattaro C, Annesi G, Melotti R, Gialluisi A, Schwienbacher C, Picard A, Blankenburg H, Pichler I, Modugno N, Ciullo M, Esposito T, Domingues FS, Hicks AA, Zappia M, Pramstaller PP. Exome-wide association study of levodopa-induced dyskinesia in Parkinson's disease. Sci Rep. 2021 Oct 1;11(1):19582. doi: 10.1038/s41598-021-99393-8.
3. Tirozzi A, Modugno N, Palomba NP, Ferese R, Lombardi A, Olivola E, Gialluisi A, Esposito T. Analysis of genetic and non-genetic predictors of levodopa induced dyskinesia in Parkinson's Disease. Front Pharmacol 2021. doi: 10.3389/fphar.2021.640603.
4. Napolitano F, Bruno G, Terracciano C, Franzese G, Palomba NP, Scotto di Carlo F, Signoriello E, De Blasiis P, Navarro S, Gialluisi A, Melone MAB, Sampaolo S, Esposito T. Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families. Int J Mol Sci. 2021 Mar 31;22(7):3625. doi: 10.3390/ijms22073625.
5. Napolitano F, Terracciano C, Bruno G, De Blasiis P, Lombardi L, Gialluisi A, Gianfrancesco F, De Giovanni D, Tummolo A, Di Iorio G, Limongelli G, Esposito T, Melone MAB, Sampaolo S. Novel autophagic vacuolar myopathies: Phenotype and genotype features. Neuropathol Appl Neurobiol. 2021 Jan 4. doi: 10.1111/nan.12690.
6. Gialluisi A, Reccia MG, Tirozzi A, Nutile T, Lombardi A, De Sanctis C; International Parkinson's Disease Genomic Consortium (IPDGC), Varanese S, Pietracupa S, Modugno N, Simeone A, Ciullo M, Esposito T. Whole Exome Sequencing Study of Parkinson Disease and Related Endophenotypes in the Italian Population. Front Neurol. 2020 Jan 10;10:1362. doi: 10.3389/fneur.2019.01362.
7. Scotto di Carlo F, Pazzaglia L, Esposito T, Gianfrancesco F. The Loss of Profilin 1 Causes Early Onset Paget's Disease of Bone. J Bone Miner Res. 2020 Jan 28. doi: 10.1002/jbmr.3964.
8. Sampaolo S, Napolitano F, Tirozzi A, Reccia MG, Lombardi L, Farina O, Barra A, Cirillo F, Melone MAB, Gianfrancesco F, Di Iorio G, Esposito T. Identification of the first dominant mutation of LAMA5 gene causing a complex multisystem syndrome due to dysfunction of the extracellular matrix. J Med Genet. 2017 Oct;54(10):710-720. IF 2017: 5.45. * Corresponding. doi: 10.1136/jmedgenet-2017-104555. Epub 2017 Jul 22. PMID: 28735299
9. Divisato G, Formicola D, Esposito T, Merlotti D, Pazzaglia L, Del Fattore A, Siris E, Orcel P, Brown JP, Nuti R, Strazzullo P, Benassi MS, Cancela ML, Michou L, Rendina D, Gennari L, Gianfrancesco F. ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor. Am J Hum Genet. 2016 Feb 4;98(2):275-86.
10. Esposito T, Sampaolo S, Limongelli G, Varone A, Formicola D, Diodato D, Farina O, Napolitano F, Gianfrancesco F, Di Iorio G. Digenic mutation inheritance of integrin alpha 7 and myosin heavy chain 7B genes causes congenital myopathy with left ventricular non compact cardiomyopathy. Orphanet J. Rare Disease 2013, Jun 21;8(1):91. doi: 10.1186/1750-1172-8-91.
11. Esposito T, Lea RA, Maher BH, Moses D, Cox HC, Magliocca C, Angius A, Nyholt DL, Titus T, Kay T, Gray NA, Rastaldi MP, Parnham A, Gianfrancesco F, Griffiths LR. Unique X-linked familial FSGS with co-segregating heart block disorder is associated with a mutation in the NXF5 gene. Hum. Mol. Genet. 2013, 22 (18): 3654-3666. doi: 10.1093/hmg/ddt215.
12. Esposito T, Rendina D, Mossetti G, De Filippo G, Gianfrancesco F, Perfetti A, Magliocca S, Formisano P, Prié D and Strazzullo P. A functional allelic variant of the FGF23 gene is associated with renal phospate leak in calcium nephrolithiasis. J Clin Endocr Metab, 2012, 97(5):E840–E844. doi: 10.1210/jc.2011-1528.
13. Esposito T, Gianfrancesco F, Ombra MN, Forabosco P, Maninchedda G, Fattorini M, Casula S, Vaccargiu S, Casu G, Cardia F, Deiana I, Melis P, Falchi M, Pirastu M. Identification of a Novel Gene and a Common Variant Associated with Uric Acid Nephrolithiasis in a Sardinian Genetic Isolate. Am. J. Hum. Genet., 2003, 72:1479-1491.
14. The International Incontinentia Pigmenti (IP) Consortium. The authors SA, HNS, ET, WH, AS, are equally first author. France (Smahi, A, Courtois G, Vabres, P, Yamaoka S, Solange Heuertz, Munnich A, and Israel A.) Germany (Heiss, NS, Klauck S, Kioschis P, Wiemann S and Poustka A.) Italy (Esposito T, Bardaro T, Gianfrancesco F, Ciccodicola A and D’Urso M.) U.K (Woffendin H, Jakins T, Donnai D, Stewart H and Kenwrick SJ.) USA (Aradhya S, Yamagata T, Levy, M, Lewis, RA and Nelson, DL.) Genomic rearrangement in Nemo impairs NF-kB activation and is a cause of incontinentia pigmenti Nature 2000, 405: 466-472. doi:10.1038/35013114
15. D'Esposito M, Ciccodicola A, Gianfrancesco F, Esposito T, Flagiello L, Mazzarella R, Schlessinger D and D'Urso M. A synaptobrevin-like gene in the Xq28 pseudoautosomal region undergoes X inactivation. Nature Genetics 1996, 13, 227-229. IF 1996: 31,473. cit 74 doi:10.1038/ng0696-227 PMID: 8640232

The complete list of publications is available on Google Scholar (Esposito Teresa profile) and at ORCID ID: http://orcid.org/0000-0002-7879-8441

Teresa Esposito is presently Senior Researcher and group leader of the Molecular Genetics and Genomics lab of the Institute of Genetics and Biophysics “Adriano Buzzati-Traverso” of the National Research Council (CNR) in Naples. She graduated in Biology at the University of Naples “Federico II” in 1992. In  1998 she completed her PhD training in Medical Embryology at University of Modena Italy and in 1999 she got her specialization in Biotechnological Applications at "Federico II" University of Naples, Italy.

From 2001 until 2004 she was Researcher at the Institute of Population Genetics of the CNR in Alghero, Italy, where she acquired a broad background in human genetics and epidemiology. In 2006 she was visiting scientist at Genomics Research Centre, Gold Coast campus, Griffith University, Australia and in 2010 at Integrative Genomics and Medicine Group MRC Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, London.

Since 2017 she is Head of the Biobank for rare disease LOPD (Late onset Pompe Disease) which also includes autophagic myopathies and member of the Board of Directors of the Biological Resources Centre (CRB) of the IGB-CNR which is part of the network of Biobanks of the BBMRI (http://www.igb.cnr.it/centro-di-risorse-biologiche).

Since 2017 she is Responsible of the CNR Research Unit at IRCCS INM Neuromed, Pozzilli (IS) focused at the realization of diagnostic protocols for an early prediction of Parkinson's disease. 

Teresa Esposito is human molecular geneticist, she has a consolidated expertise in the identification of genes and genetic variants related to human disease. Since 2012 she has moved on the world of “omics” technology by using next generation sequencing approach to identify genes/variants associated to human diseases.

Other experiences

Instructor at the Theoretical and Practical Course Embo "Cloning into YAC vectors III", IIGB-CNR, Naples Italy (1994).

Instructor at the Theoretical and Practical Course Embo "Cloning into YAC vectors II", IIGB-CNR, Naples Italy (1992).

Member of the Italian Society of Human Genetics S.I.G.U 1994-2000 and 2016- to date

Member of the American Society of Human Genetics ASHG 2006- to date

Member of the Forum in Bone and Mineral Research 2007-to date

Member of the National Incontinenia Pigmenti Foundation 1998-2001

Tutor of PhD program in Molecular and Cellular Biotechnology of the Second University of Naples (2013-to data).

International Evaluator of Doctoral Thesis of the Griffith University (Australia), Years: 2011 and 2014.

Publications

Author of 85 publications and two patents: PCT/IT2003/000627 and RM2002A000525.

H-Index: 25 (WOS)

Scopus Author Id: 56213303300

ORCID ID: http://orcid.org/0000-0002-7879-8441

Selected Research Support

PI Coordinator: Assessing the polygenic burden of rare disruptive mutations in Parkinson's disease: a novel diagnostic test to predict Parkinson's disease risk. Prog n. RF-2019-12370224, funded by the Ministry of Health (Ricerca Finalizzata 2019).

Co-PI: Genomica Funzionale di malattie genetiche rare: Realizzazione di strumenti innovativi ad alto potere diagnostico. (2019-2022) Prog n. F/050011/01/X32, funded  by MISE.

Co-PI: Approccio multidisciplinare per la realizzazione di protocolli diagnostici per la predizione precoce di predisposizione al morbo di Parkinson (2014-2018) Invitalia – Agenzia per lo sviluppo.

Co-PI : Realizzazione di strumenti diagnostici per l'analisi precoce del morbo di Parkinson attraverso l'identificazione di profili genetici di rischio (2015-2018) MISE – Ministry of Economic Development.

Unit Participant: Dissecting the molecular mechanism of skeletal neoplastic conditions associated with Paget's disease of bone (2014-2017) AIRC

Principal Investigator: Genetic analysis and genotype-phenotype correlations of an extended Italian family with late onset glycogen storage disease tipe II (Pompe disease). (2013-2016) Genzyme-Sanofi Company

Unit Participant: Genetics and Pharmacogenetics of Paget's Disease of Bone. (2011-2013) Telethon Project GGP11119

Principal Investigator: Sequencing and Bioinformatics analysis of two Australian patients affected by Focal Segmental Glomerulosclerosis. (2011). Genomics Research Centre, School of Medical Science, Griffith University, Queensland Australia

Unit Participant: Griffith University, Australia, project: An international strategy to identify the genes involved in Migraine. (Period: 2009-2011).