Research Interests

 

Effect of low dose radiations on stem cells: what is the contribution of senescence associated secretory phenotype (SASP)?

Low doses of radiation may have profound effects on cellular function. Individuals may be exposed to low doses of radiation either intentionally for medical diagnosis (e.g. X-rays and computed tomography (CT) scans) or accidentally, such as those exposed to radiological terrorism or those who live near illegal radioactive waste dumpsites. Stem cells are among the major targets of low dose radiation, since they may undergo progressive accumulation of DNA damage given their long half-life.  We studied the effects of low dose radiation on human bone marrow mesenchymal stromal cells (MSCs), which contain a subpopulation of stem cells able to differentiate in bone, cartilage, and fat; support hematopoiesis; and contribute to the homeostatic maintenance of many organs and tissues. Currently we are interested on the effect of low dose radiation on microvesicles and exosome (secretome) composition and functionality.  In some cell types, such as MSCs, low dose radiations induce senescence rather than apoptosis. Senescent cells  exert their effect on neighbour and distant cells by releasing exosomes. For this reason, side and bystander effects of low dose radiation are strictly associated to secreted factors released by irradiated cells.

Senescence of stem cells and related pathways: DNA repair, autophagy, secretome (exosomes), metabolism

Mesenchymal stem cells (MSCs) are of particular interest because they are being tested in cell and gene therapy for a number of human diseases. MSCs represent a rare population in tissues. Therefore, it is essential to grow MSCs in vitro before putting them to therapeutic use. This is compromised by senescence, limiting the proliferative capacity of MSCs. We are studying the in vitro senescence of MSCs.  We are also interested in evaluating the role of senescent MSCs in the aging of tissues and organs. We study several aspects of senescence, such as replicative chronic senescence and stress-induced acute senescence. In particular, we study effects of low and high dose radiations on MSC functions. Our investigations aims to:

  • analyze  molecular pathways involved in DNA repair, whose activity is downregulated with aging or following  stress-induced senescence;  
  • evaluate relationship between autophagy process and senescence;
  • senescence is not a cell-autonomous phenomenon. Senescent cells secrete a plethora of factors that, in paracrine manner, affect the function of neighbour cells. We are studying the secretome of senescent MSCs. This a very hot topic, since MSCs act mainly by paracrine function and senescence greatly affects secretome of MSCs;
  • every cell status is sustained by specific cell metabolism processes, we are interested in evaluating metabolic changes that trigger and/or are consequence of senescence. 

Epigenetic regulation of stem cell biology

Chromatin state is fundamental for gene expression. Self-renewal, proliferation and differentiation properties of stem cells are controlled by key transcription factors. However, their activity is modulated by chromatin remodeling factors that operate at the highest hierarchical level. Studies on these factors can be especially important to dissect molecular pathways governing the biology of stem cells.

  • SWI/SNF complexes are ATP-dependent chromatin remodeling enzymes that have been shown to be required for cell cycle control, apoptosis and cell differentiation in several biological systems. The aim of our research was to investigate the role of these complexes in the biology of MSCs.
  • DNA methylation is an epigenetic modification that occurs almost exclusively in the context of CpG dinucleotides. MECP2 is a member of a family of proteins that preferentially bind to methylated CpGs. We are analyzing the specific contribution of MECP2 in physiology of mesenchymal stem cells (MSCs).
  • Histone deacetylase inhibitors (HDACi) have received great attention for their anti-tumoral properties. This anti-cancer action can be obtained by reversion of silenced genes, induction of cell cycle arrest, differentiation and/or apoptosis. HDACi-based therapy can have side effects that impair functions of bone marrow microenvironment, including MSCs. We are studying the biological effects of HDACi on MSCs.

Mesenchymal stem cells from basic to applied sciences

 Restenosis following vascular injury remains a pressing clinical problem, despite continuous improvements of medical strategies. The possible therapeutic role of MSCs in a model of vascular injury in vivo has not been determined so far. We are testing the homing and the effectiveness of MSCs in reduction of (re)stenosis in a model of arteriotomy of rat common carotid.

Studies on Retinoblastoma gene family

Our group is interested in the studies on genes involved in cell cycle regulation, differentiation, apoptosis and senescence such as the Retinoblastoma (RB) family.We have evaluated the role of Retinoblastoma genes in the regulation of cell proliferation, differentiation and apoptosis in cancer and normal stem cells. In detail, our group has analyzed the biology of neural stem cells and mesenchymal stem cells. These studies prompted the attention also on chromatin remodeling factors that interact with RB family members and play a key role in the life of stem cells.

Ancient DNA - Is this an Intruder?

We are molecular biologists, we are curious persons, we live near Vesuvius and near Pompeii archeological site, we are fascinated by history. Mix up all these ingredients and it will prompt our research on ancient DNA. 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. We have started genetic characterization of equids discovered in a Pompeii stable and of ancient Pompeii inhabitants. Ancient DNA for analyses is obtained by skeletons buried by the eruption of  Vesuvius in 79 AD.

 

EXPERTISES

Our Laboratories at the Second University of Naples are fully equipped with facilities for extraction and analysis of nucleic acids and proteins, as well as for cell biology analyses and for stem cell cultures.

Our Researchers have expertise in

  • cultivation of adult stem cells (mesenchymal, muscle satellite and neural stem cells)
  • gene expression analysis by quantitative RT-PCR and microarrays
  • chromatin studies: CHIP assay, CHART-PCR assay, DNA methylation assay
  • protein expression by Western blots, ELISA assays and immunocytochemistry
  • biological assay to analyze apoptosis, senescence, proliferation, cell cycle
  • detection of DNA damage by several assays
  • evaluation of autophagy and proteosome activities
  • evaluation of cellular metabolism: analysis of Glycolysis, Tricyclic Acid Cycle, Fatty Acid Oxidation, ATP production

 

 

 

 

 
 
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