Umberto Galderisi

Professor of Molecular Biology

Name Umberto
Surname Galderisi
Institution Università degli Studi della Campania Luigi Vanvitelli
Telephone +39 081 566 75 85
E-Mail umberto.galderisi@unicampania.it
Address Dept. of Experimental Medicine, Via Luigi De Crecchio 7 – 80138 Napoli, Italy
Umberto Galderisi

Member PUBLICATIONS

  • Differential expression of multiple transglutaminases in human colon: impaired keratinocyte transglutaminase expression in ulcerative colitis.

    Publication Date: 01/04/2005 on Gut
    by D'Argenio G, Calvani M, Della Valle N, Cosenza V, Di Matteo G, Giorgio P, Margarucci S, Petillo O, Jori FP, Galderisi U, Peluso G
    DOI: 10.1136/gut.2004.049411

    Ulcerative colitis (UC) is characterised by refractory inflammatory ulceration and damage to the colon. The mechanisms underlying impaired healing have yet to be defined. As transglutaminase expression resulting in matrix protein cross linking is associated with increased wound healing in a rat model of colitis, we hypothesised that different types of transglutaminase might also play a role in UC.

  • Methods to improve the yield and quality of DNA from dried and processed figs.

    Publication Date: 01/03/2005 on Biotechnology progress
    by Di Bernardo G, Galderisi U, Cipollaro M, Cascino A
    DOI: 10.1021/bp049710p

    We describe here a molecular method that can be used to detect genome traits of a given horticultural item at each stage from the farm to the market. We developed a procedure to extract and amplify by PCR DNA obtained from complex matrixes, such as dried figs and fig jam. Few fragmented DNA molecules can be recovered from food products. However, we were able to increase the yield of PCR reactions by successfully applying an enzymatic repair protocol to retrieved DNA.

  • Molecular pathways involved in neural in vitro differentiation of marrow stromal stem cells.

    Publication Date: 01/03/2005 on Journal of cellular biochemistry
    by Jori FP, Napolitano MA, Melone MA, Cipollaro M, Cascino A, Altucci L, Peluso G, Giordano A, Galderisi U
    DOI: 10.1002/jcb.20315

    In recent years several reports have claimed to demonstrate trans-differentiation, namely that stem cells have been derived from a given tissue and have differentiated into phenotypes characteristic of different tissues following transplantation or in vitro treatment. For example, the mesenchymal stem cells, also referred to as marrow stromal stem cells (MSCs), present in bone marrow, have been induced to differentiate into neurons. We decided to investigate this phenomenon more in depth by a molecular and morphological follow-up. We analyzed the biochemical pathways that are currently induced to trigger neuron-like commitment and maturation of MSCs. Our studies suggest that: (i) the increase in cAMP, induced to differentiate MSCs, activates the classical PKA pathway and not through the exchange protein directly activated by cAMP (EPAC), a guanine nucleotide exchange factor for the small GTPase Rap1 and Rap2; (ii) MEK-ERK signaling could contribute to neural commitment and differentiation; (iii) CaM KII activity seems dispensable for neuron differentiation. On the contrary, its inhibition could contribute to rescuing differentiating cells from death. Our research also indicates that the currently used in vitro differentiation protocols, while they allow the early steps of neural differentiation to take place, are not able to further sustain this process.

  • Small interfering RNAs and antisense oligonucleotides for treatment of neurological diseases.

    Publication Date: 01/02/2005 on Current drug targets
    by Forte A, Cipollaro M, Cascino A, Galderisi U

    The complexity of the central nervous system (CNS) exposes it to a number of different diseases, often caused by only small variations in gene sequence or expression level. Antisense oligonucleotides and RNA interference-mediated therapies hold great promise for the treatment of CNS diseases in which neurodegeneration is linked to overproduction of endogenous protein or to synthesis of aberrant proteins coded by dominant mutant alleles. Nevertheless, difficulties related to the crossing of the blood-brain barrier, expression vectors, molecule design and to the choosing of the correct target, should be effectively solved. This review summarizes some of the most recent findings concerning the administration of potential nucleic acid-based therapeutic drugs, as well as the most promising studies performed both in vitro and in animal models of disease. Finally, some current clinical trials involving antisense oligonucleotides or silencing RNA for therapy of neurological disorders are illustrated. Results of current studies and clinical trials are exciting, and further results will be certainly reached with increasing knowledge of blood-brain barrier transporters, of genes involved in neurological disease and in new vectors for efficient delivery to brain.

  • Ancient DNA as a multidisciplinary experience.

    Publication Date: 01/02/2005 on Journal of cellular physiology
    by Cipollaro M, Galderisi U, Di Bernardo G
    DOI: 10.1002/jcp.20116

    Investigation into DNA from archeological remains offers an inestimable tool for unraveling the history of humankind. However, a series of basic and technical difficulties renders the analysis of ancient DNA (aDNA) molecules troublesome, depending either on their own peculiar characteristics or on the complexity of processes affecting the bone matrix over time, all compromising the preservation of ancient DNA. This review underlines the contribution of many different disciplines, in particular molecular biology and genetics, to overcome these obstacles. The role of each expertise is illustrated to appropriately address the questions arising in aDNA investigations.

  • RB and RB2/p130 genes demonstrate both specific and overlapping functions during the early steps of in vitro neural differentiation of marrow stromal stem cells.

    Publication Date: 01/01/2005 on Cell death and differentiation
    by Jori FP, Melone MA, Napolitano MA, Cipollaro M, Cascino A, Giordano A, Galderisi U
    DOI: 10.1038/sj.cdd.4401499

    Marrow stromal stem cells (MSCs) are stem-like cells that are currently being tested for their potential use in cell therapy for a number of human diseases. MSCs can differentiate into both mesenchymal and nonmesenchymal lineages. In fact, in addition to bone, cartilage and fat, it has been demonstrated that MSCs are capable of differentiating into neurons and astrocytes. RB and RB2/p130 genes are involved in the differentiation of several systems. For this reason, we evaluated the role of RB and RB2/p130 in the differentiation and apoptosis of MSCs under experimental conditions that allow for MSC differentiation toward the neuron-like phenotype. To this end, we ectopically expressed either RB or RB2/p130 and monitored proliferation, differentiation and apoptosis in rat primary MSC cultures induced to differentiate toward the neuron-like phenotype. Both RB and RB2/P130 decreased cell proliferation rate. In pRb-overexpressing cells, the arrest of cell growth was also observed in the presence of the HDAC-inhibitor TSA, suggesting that its antiproliferative activity does not rely upon the HDAC pathway, while the addition of TSA to pRb2/p130-overexpressing cells relieved growth inhibition. TUNEL reactions and studies on the expression of genes belonging to the Bcl-2 family showed that while RB protected differentiating MSCs from apoptosis, RB2/p130 induced an increase of apoptosis compared to controls. The effects of both RB and RB2/p130 on programmed cell death appeared to be HDAC- independent. Molecular analysis of neural differentiation markers and immunocytochemistry revealed that RB2/p130 contributes mainly to the induction of generic neural properties and RB triggers cholinergic differentiation. Moreover, the differentiation potentials of RB2/p130 and RB appear to rely, at least in part, on the activity of HDACs.

  • 2000 Year-old ancient equids: an ancient-DNA lesson from pompeii remains.

    Publication Date: 15/11/2004 on Journal of experimental zoology. Part B, Molecular and developmental evolution
    by Di Bernardo G, Del Gaudio S, Galderisi U, Cipollaro M
    DOI: 10.1002/jez.b.21017

    Ancient DNA extracted from 2000 year-old equine bones was examined in order to amplify mitochondrial and nuclear DNA fragments. A specific equine satellite-type sequence representing 3.7%-11% of the entire equine genome, proved to be a suitable target to address the question of the presence of aDNA in ancient bones. The PCR strategy designed to investigate this specific target also allowed us to calculate the molecular weight of amplifiable DNA fragments. Sequencing of a 370 bp DNA fragment of mitochondrial control region allowed the comparison of ancient DNA sequences with those of modern horses to assess their genetic relationship. The 16S rRNA mitochondrial gene was also examined to unravel the post-mortem base modification feature and to test the status of Pompeian equids taxon on the basis of a Mae III restriction site polymorphism.

  • Role of RB and RB2/P130 genes in marrow stromal stem cells plasticity.

    Publication Date: 01/08/2004 on Journal of cellular physiology
    by Jori FP, Napolitano MA, Melone MA, Cipollaro M, Cascino A, Giordano A, Galderisi U
    DOI: 10.1002/jcp.20026

    Marrow stromal cells (MSCs) are stem-like cells having a striking somatic plasticity. In fact, besides differentiating into mesenchymal lineages (bone, cartilage, and fat), they are capable of differentiating into neurons and astrocytes in vitro and in vivo. The RB and RB2/P130 genes, belonging to the retinoblastoma gene family, play a key role in neurogenesis, and for this reason, we investigated their role in neural commitment and differentiation of MSCs. In MSCs that were either uncommitted or committed toward neural differentiation, we ectopically expressed RB and RB2/P130 genes and analyzed their role in regulating the cell cycle, apoptosis and differentiation. In uncommitted MSCs, the activity of RB and RB2/P130 appeared limited to negatively regulating cell cycle progression, having no role in apoptosis and differentiation (toward either mesenchymal or neural lineages). On the other hand, in MSCs committed toward the neural phenotype, both RB and RB2/P130 reduced cell proliferation rate and affected the apoptotic process. RB protected differentiating cells from programmed cell death. On the contrary, RB2/P130 increased the percentage of cells in apoptosis. All of these activities were accomplished mainly in an HDAC-independent way. The retinoblastoma genes also influenced differentiation in neural committed MSCs. RB2/P130 contributes mainly to the induction of generic neural properties, while RB triggers cholinergic differentiation. These differentiating activities are HDAC-dependent. Our research shows that there is a critical temporal requirement for the RB genes during neuronal differentiation of MSCs: they are not required for cell commitment but play a role in the maturation process. For the above reasons, RB and RB2/P130 may have a role in neural differentiation but not in neural determination.

  • Genetic characterization of Pompeii and Herculaneum Equidae buried by Vesuvius in 79 AD.

    Publication Date: 01/05/2004 on Journal of cellular physiology
    by Di Bernardo G, Galderisi U, Del Gaudio S, D'Aniello A, Lanave C, De Robertis MT, Cascino A, Cipollaro M
    DOI: 10.1002/jcp.10461

    DNA extracted from the skeletons of five equids discovered in a Pompeii stable and of a horse found in Herculaneum was investigated. Amino acid racemization level was consistent with the presence of DNA. Post-mortem base modifications were excluded by sequencing a 146 bp fragment of the 16S rRNA mitochondrial gene. Sequencing of a 370 bp fragment of mitochondrial (mt)DNA control region allowed the construction of a phylogenetic tree that, along with sequencing of nuclear genes (epsilon globin, gamma interferon, and p53) fragments, gave us the possibility to address some questions puzzling archaeologists. What animals-donkeys, horses, or crossbreeds-were they? And, given they had been evidently assigned to one specific job, were they all akin or were they animals with different mitochondrial haplotypes? The conclusions provided by molecular analysis show that the Pompeii remains are those of horses and mules. Furthermore one of the equids (CAV5) seems to belong to a haplotype, which is either not yet documented in the GenBank or has since disappeared. As its characteristics closely recall those of donkeys, which is the out group chosen to construct the tree, that appears to have evolved within the Equidae family much earlier than horses, this assumption seems to be nearer the truth.

  • Stenosis progression after surgical injury in Milan hypertensive rat carotid arteries.

    Publication Date: 01/12/2003 on Cardiovascular research
    by Forte A, Esposito S, De Feo M, Galderisi U, Quarto C, Esposito F, Renzulli A, Berrino L, Cipollaro M, Agozzino L, Cotrufo M, Rossi F, Cascino A

    Milan hypertensive rats (MHS) are characterised by an increase in renal sodium reabsorption mainly related to adducin mutations. Interest in this model relies on the genetic link between adducin polymorphisms and primary hypertension, observed also in a subset of patients.