Germana Meroni
Germana Meroni
affiliation: CBM - Cluster in Biomedicine, AREA Science Park, Trieste
research area(s): Genetics And Genomics, Molecular Biology
Course: Molecular Biomedicine
University/Istitution: Università di Trieste
1988 Degree (Laurea) in Biological Sciences, Summa Cum Laude , University of Milan.

1988-1991 Pre-doctoral Fellow at DIBIT, S. Raffaele Biomedical Science Park, Milan.
1991-1994 Post-doctoral Fellow at DIBIT, S. Raffaele Biomedical Science Park, Milan.
1994-1995 Postdoctoral Fellow at the Dept. of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX (USA).
1995- 2000 Researcher, Telethon Institute of Genetics and Medicine (TIGEM), Milan, Italy
2000-09June Group leader, Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy
2009July- Group leader, Cluster in Biomedicine – (CBM) AREA Science Park, Trieste.

Member of the Targeted protein Database UPS Virtual Faculty and Ubiquitin Journal Editorial Board (Current Biodata – BioMed Central) since 2006.

Ad Hoc Reviewer for: American Journal of Medical Genetics, Biochimica et Biophysica Acta, Biochemical Journal, BioEssay, BMC Evolutionary Biology, Development, European Journal of Human Genetics, Experimental Cell Research, FEBS Journal, Gene Expression Patterns, Human Molecular Genetics, Human Genetics, J. of the European Academy of Dermatology and Venereology (JEADV), Journal of Human Genetics, Nature Reviews Cancer, Oncogene, Molecular and Cellular Biology

Ad Hoc Grant Reviewer: The Leverhulme Trust, London, UK; MIUR – COFIN, Italy; Cancer Research UK; MRC, UK; Austrian Science Fund (FWF), Austria

Lecturer for the PhD program of the European School of Molecular Medicine (SEMM), Milan and Naples, Italy from 2005 to 2009.
PhD Thesis evaluations:
External evaluator for PhD theses at the Quaid-i-Azam University, Islamabad, Pakistan and University of Balochistan, Quetta, Pakistan (Muhammad Arshad Rafiq, Salma Sultana, Asif Mir, Abdul Wali, Muhammad Ayub)

Internal examiner for the degree of Master of Phylosophy of the Open University, London, UK (Hannah Margareta Teichmann)

Post-graduate Supervisor: Silvia Cainarca, Residency in Applied Genetics (2000); Stefano Cairo, PhD Open University (2003); Caterina Berti, Residency in Medical Genetics (2004); Luisa MR Napolitano, PhD Open University (present); Alessio Lancioni, PhD University of Pisa (2011).
Systematic study of the Tripartite motif (TRIM) family
The TRIM family represents a sub-class of RING finger proteins that are characterized by the presence of the Tripartite motif, which consists of a RING domain, one or two B-box motifs and a coiled-coil region. Genes that belong to this family are implicated in several inherited human diseases (Familial Mediterranean Fever, X-linked Opitz syndrome, and Mulibrey nanism). We used a systematic approach to identify and collect the cDNA of 30 TRIM genes. We found that the TRIM proteins have a strong self-association ability that is mediated by their coiled-coil region. This property results in the formation of large protein complexes that identify diverse discrete sub-cellular structures. Recent data indicate that TRIM proteins share a common biochemical function acting as E3 ubiquitin ligases. The large number of proteins of this family, the more numerous class of single protein RING finger E3s, highlights the success of the tripartite module to undertake this task. The TRIM proteins have precisely maintained the basic structure and evolved the intervening sequences to recognize in a specific manner their substrates. We are interested to trace the evolution of the TRIM genes especially in light of their participation in the ubiquitylation process. To this purpose we have performed in silico searches to identify all the human TRIM genes, approximately 70 members, and along the same line we are searching family members in several other species. We will comprehensively examine this family in term of genomic clustering and peptide sequences, redefining the domains that compose the tripartite motif. Focusing on the human members, we are also interested in i) evaluating the putative effect of non-homologous regions on the domain configuration also with the support of modeling on pre-existing solved structures; ii) testing specific interaction between the TRIM proteins and ubiquitylation machinery components, data that will be confronted to bioinformatics results.
The role of the Opitz Syndrome gene MID1 in midline development
Opitz syndrome (OS) is a multiple congenital anomaly manifested by abnormal closure of midline structures. The gene responsible for the X-linked form of this disease, MID1, encodes a protein that contains a tripartite motif. We found that Mid1 homo-interacts and forms high molecular weight complexes that are anchored to the microtubular apparatus. In mutants that reproduce OS patients’ MID1 alterations, the association with the microtubules is compromised. The association of the wild-type protein to the microtubules is regulated by its phosphorylation status through direct interaction with the alpha4 subunit of phosphatase 2A (PP2A). Mid1 acts as an ubiquitin E3 ligase that regulates the level of PP2A anchored to the microtubules though the consequence of an altered microtubular PP2A is yet to be determined. To get insights into the role of MID1 in both normal and pathological conditions, our research is focused on i) the characterization of additional Mid1 partners to reconstruct Mid1 cellular pathway; ii) the evaluation of the implication of genes encoding for these partners in the pathogenesis of OS patients that result non-mutated in the MID1 gene; iii) the thorough study of the embryonic development of a mouse line we have generated and that bears a disrupted MID1 gene.
Mussolino C., Sanges D., Marrocco E., Bonetti C., Di Vicino U., Marigo V., Auricchio A., Meroni G., Surace EM. (2011). Zinc-finger-based transcriptional repression of rhodopsin in a model of dominant retinitis pigmentosa. EMBO Molecular Medicine, 3(3):118-28.

Napolitano LM, Jaffray EG, Hay RT, Meroni G. (2011). Functional interactions between ubiquitin E2 enzymes and TRIM proteins. Biochemical J. Feb 11;434(2):309-19.

Ruiter M., Kamsteeg E., Meroni G., de Vries BBA. (2010). A MID1 mutation associated with reduced penetrance of X-linked Opitz G/BBB syndrome. Clinical Dysmprphology, Oct;19(4):195-7

Lancioni A., Pizzo M., Fontanella B., Ferrentino R., Napolitano LMR., De Leonibus E., Meroni G. (2010). Lack of Mid1, the mouse ortholog of the Opitz Syndrome gene, causes abnormal development of the anterior cerebellar vermis. J Neuroscience, Feb 24, 30(8):2880-2887

Sardiello M, Cairo S, Fontanella B, Ballabio A, Meroni G. (2008). Genomic analysis of the TRIM family reveals two groups of genes with distinct evolutionary properties. BMC Evolutionary Biology, 8:225

Micale L, Fusco C, Augello B, Napolitano LMR, Dermitzakis ET, Meroni G, Merla G, and Reymond A. (2008). Williams-Beuren syndrome TRIM50 encodes an E3 ubiquitin ligase. European Journal of Human Genetics, Sep;16(9):1038-49

Fontanella B, Russolillo G, Meroni G. (2008). MID1 mutations in patients with X-linked Opitz G/BBB Syndrome. Human Mutation, May;29(5):584-94

Ferrentino R, Bassi MT, Chitayat D, Tabolacci E, Meroni G. (2007). MID1 Mutation Screening in a Large Cohort of Opitz G/BBB Syndrome Patients: Twenty-nine Novel Mutations Identified. Human Mutation Feb 28(2):206-207

Procaccio V, Salazar G, Ono S, Styers ML, Gearing M, Davila A, Jimenez R, Juncos J, Gutekunst CA, Meroni G, Fontanella B, Sontag E, Sontag JM, Faundez V, Wainer BH. (2006). A mutation of beta-actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia. American Journal of Human Genetics, 78, 947-960.

Meroni G and Diez-Roux G. (2005). TRIM/RBCC, a novel class of ‘single protein RING finger’ E3 ubiquitin ligases. BioEssays (2005) 27(11):1147-1157.

S. Cairo, F. De Falco, M. Pizzo, P. Salomoni, P.P. Pandolfi, G. Meroni. (2005) PML interacts with Myc, and Myc target gene expression is altered in PML null fibroblasts. Oncogene 24(13):2195-203.

C. Berti, B. Fontanella, R. Ferrentino, G. Meroni. (2004) Mig12, a novel Opitz syndrome gene product partner, is expressed in the embryonic ventral midline and co-operates with Mid1 to bundle and stabilize microtubules. BMC Cell Biology 5:9.

F. De Falco, S. Cainarca, G. Andolfi, R. Ferrentino, C. Berti, G. Rodríguez Criado, O. Rittinger, N. Dennis, S. Odent, A. Rastogi, J. Liebelt, D. Chitayat, R. Winter, H. Jawanda, A. Ballabio, B. Franco, G. Meroni. (2003). X-linked Opitz syndrome: novel mutations in the MID1 gene and redefinition of the clinical spectrum. American Journal of Medical Genetics 120A(2):222-8

C. Berti, S. Messali, A. Ballabio, A. Reymond, G. Meroni. (2002) TRIM9 is specifically expressed in the embryonic and adult nervous system. Mechanisms of Development 113, 159-162.

J. Liu, T. Prickett, L. Elliott, G. Meroni and D. Brautigan. (2001) Phosphorylation and Microtubule Association of the Opitz syndrome protein Mid1 is regulated by Protein Phosphatase 2A via binding to the regulatory subunit alpha4. Proc. Nat. Acad. Sci. USA 5;98(12), 6650-6655.

Reymond*, G. Meroni*, A. Fantozzi, G. Merla, S. Cairo, L. Luzi, D. Riganelli, E. Zanaria, S. Messali, S. Cainarca, A. Guffanti, S. Minucci, P. G. Pelicci and A. Ballabio (2001). The Tripartite Motif Family identifies Cell Compartments. The EMBO Journal 20, 2140-2151.

G. Meroni, S. Cairo, G. Merla, S. Messali, R. Brent, A. Ballabio and A. Reymond. (2000) Mlx, a new Max-like bHLHZip family member: the center stage of a novel transcription factors regulatory pathway? Oncogene 19, 3266-3277.
No projects are available to students for the current accademic year.