Patrizia Malaspina
Patrizia Malaspina
affiliation: Università di Roma Tor Vergata
research area(s): Genetics And Genomics, Molecular Biology
Course: Cell and Molecular Biology
University/Istitution: Università di Roma Tor Vergata
1992 Degree of Specialization (Scuola di Specializzazione) in Medical Genetics (70/70 cum laude), University "La Sapienza", Rome, Italy.
1989 Ph.D. (Dottorato di ricerca) in Medical Genetics, University "La Sapienza", Rome, Italy.
1980 Degree (Laurea) in Biological Sciences (110/110 cum laude), University "La Sapienza", Rome, Italy.

2002 to present Associate Professor of Genetics, Department of Biology, University "Tor Vergata", Rome, Italy.
1994-2001 Assistant Professor of Genetics, Department of Biology, University "Tor Vergata", Rome, Italy.
1989-1992 Post-Doc fellow, Department of Biology, University "Tor Vergata", Rome, Italy.
1985-1989 Ph.D. student, Department of Biology, University "Tor Vergata", Rome, Italy.
1983-1985 Research fellow, Department of Biology and Genetics, University of Naples, Italy.
1976-1980 Student in Biological Sciences, University "La Sapienza" Rome, Italy.

2001 Visiting researcher, Dept. of Molecular and Medical Gentics, OHSU, Portland, OR, USA.
1991-1992 Research fellow at the MRC Human Biochemical Genetic Unit, University College, London, U.K.
1987 Honorary research assistant at the Galton Laboratory, Dept. of Genetics and Biometry, University College, London, U.K.

2001 CNR Short term mobility fellowship with the project "Molecular characterization of 4-hydroxybutyric aciduria patients" at Dept. of Molecular and Medical Genetics, OHSU, Portland, OR, USA.
1994 Fellowship issued by "Fondazione Adriano Buzzati-Traverso" for the project titled "Spinocerebellar ataxia (SCA1) in two large Italian kindreds".
1991-1992 Bursary issued by EEC in the "Human Genome Analysis Program"
The major goal of the human genome project was the acquisition of fundamental information concerning our genetic composition which represents the basis to understand the role of various genes in humans. Furthermore, the identification of a very large number of nucleotide polymorphisms across the genome allows the analysis of human diversity and represents an invaluable tool for anthropological and medical research. Inherited differences in DNA sequence contribute to phenotypic variation, influencing individual"s characteristics such as susceptibility to diseases or differential response to metabolites and drugs.

Our specific interests
Our line of research is aimed at the study of the catabolism of gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in human central nervous system. GABA is present in the brain in large amounts and distributed among distinctly different cellular pools, possibly reflecting its multiple functions as metabolite, neurotransmitter, and neurotrophin.
Our interest in GABA catabolism has evolved from the study at molecular and physiological level of SSADH, a mitochondrial enzyme that irreversibly catalyses the oxidation of succinic semialdehyde to succinate, the final step of the GABA degradative pathway. Complete deficiency of SSADH results in a rare autosomal recessive disease called gamma-hydroxybutyric aciduria (4-HBA) for the abnormal accumulation of GHB in the brain of patients. GHB possesses a number of unusual neuropharmacological properties, it is used to treat narcolepsy, alcohol and opiate withdrawal, and as a drug of abuse linked to its putative euphoric effects.
We mapped the human SSADH gene in chromosome 6p22 and characterized its genomic and coding structure.
Our group studied the pathological variation of SSADH and described disease-causing mutations in about fifty 4-HBA families ; we also identified naturally occurring variants in the general population that determine a decrease of the enzyme activity as low as 40% of normal. This would indicate an inter-individual variation in the endogenous production of GHB and GABA.
Moreover, SSADH occupies a further role in the central nervous system as the enzyme responsible for further metabolism of the lipid peroxidation aldehyde 4-hydroxy-2-nonenal (4-HNE), an intermediate known to reduce oxidant stress. Accordingly, subtle decreases in SSADH activity may have the capacity to lead to regional accumulation of neurotoxic intermediates (GHB, 4-HNE).
At present, our studies are focused on:
- The study of the effects of endogenous and exogenous metabolites, enzymes and inhibitors of GABA catabolism on GABA-T, SSADH and AKR7A2 gene expression;
- The identification of molecular variants of SSADH, GABA-T and AKR7A2 genes that could influence the endogenous GABA and GHB levels and be responsible of clinical and subclinical phenotypes.
1)BLASI P., PALMERIO F., AIELLO A., ROCCHI M., MALASPINA P., NOVELLETTO A. (2006) SSADH variation in primates: intra and inter specific data on a gene with a potential role in human cognitive functions. J. Mol. Evol. 63:54-68. ISSN: 0022-2844.

Succinic semialdehyde dehydrogenase (SSADH) deficiency: clinical, biochemical and molecular characterization of a new patient with severe phenotype and a novel mutation. Clin. Genet. 69:294-296. ISSN: 0009-9163.
3)LEMES A., BLASI P., GONZALES G. , RUSSI M.E., QUADRELLI R., NOVELLETTO A., MALASPINA P. (2006) Succinic semialdehyde dehydrogenase (SSADH) deficiency: molecular analysis in a South American family.. J. Inherit. Metab. Dis. 29:587. ISSN: 0141-8955.
4)LEONE O., BLASI P., PALMERIO F., KOZLOV A.I., MALASPINA P., NOVELLETTO A. (2006) A human derived SSADH coding variant is replacing the ancestral allele shared with primates. Ann. Hum. Biol. 33:593-603. ISSN: 0301-4460.
5)LUCA F., DI GIACOMO F., BENINCASA T., POPA L.O., BANYKO J., KRACMAROVA A., MALASPINA P., NOVELLETTO A., BRDICKA R. (2007) Y-chromosomal variation in the Czech Republic. Am. J. Phys. Anthrop. 132:132-139. ISSN: 0002-9483.

6)LEUZZI V., DI SABATO M.L., DEODATO F., RIZZO C., BOENZI S., CARDUCCI C., MALASPINA P., LIBERANOME C., DIONISI-VICI C. (2007) Vigabatrin improves paroxysmal dystonia in succinic semialdehyde dehydrogenase deficiency. Neurology 68:1320-1321. ISSN: 0028-3878.

7)MALASPINA P., PICKLO M.J., JAKOBS C., SNEAD O.C. 3rd , GIBSON K.M. (2009) Comparative genomics of aldehyde dehydrogenase 5A1 (succinate semialdehyde dehydrogenase) and accumulation of gamma-hydroxybutyrate associated with its deficiency. Human Genomics 3:106-120. ISSN: 1479-7364.

8)DI ROSA G., MALASPINA P., BLASI P., DIONISI-VICI C., RIZZO C., TORTORELLA G., CRUTCHFIELD S.R., GIBSON K.M. (2009) Visual Evoked Potentials in Succinate Semialdehyde Dehydrogenase (SSADH) Deficiency. J. Inherit. Metab. Dis. ISSN: 0141-8955. doi: 10.1007/s10545-009-1154-4

9)KIM K.J., PEARL P.L., JENSEN K, SNEAD O.C. 3RD, MALASPINA P., JAKOBS C., GIBSON K.M. (2010) Succinic Semialdehyde Dehydrogenase (SSADH): Biochemical-Molecular-Clinical Disease Mechanisms, Redox Regulation and Functional Significance. Antioxidants & Redox Signaling (in press).

10) NOVELLETTO A., GULLI R., CIOTTI P., VITALE C., MALASPINA P., BLASI, P, et al. (2011). Linkage exclusion in Italian families with hereditary Essential Tremor. European Journal of Neurology (in press).
No projects are available to students for the current accademic year.