Research activities

Main Research Center - Segrate:

The Genomics Lab employs state of the art technologies in nucleic acids analysis in several different application fields, developing methods and bioinformatics tools needed in each specific project. Whole genome sequencing of bacteria for biotech and clinical applications and targeted human genome resequencing for the identification of genetic determinants in genetic diseases and cancer are two of the main fields of research. Recently, epigenomics in human cells and research in microbial diversity and microbiome analysis in the gut has been an additional focus of the group in relationship with disease state in patients. A diverse field of application consists in ancient DNA identification in evolutionary studies.
Thanks to these efforts, a acknowledged expertise have been gained at the national and international level within the diverse application fields (whole genome sequencing, whole transcriptome sequencing, chromatin immunoprecipitation sequencing etc) either for molecular and bioinformatics skills yielding long-lasting collaborations with academic and industrial partners. As an example we could cite the studies in human genetic diseases (multiple sclerosis, amyotrophic lateral sclerosis, Brugada syndrome, Congenital Hyperinsulinism), cancer (melanoma, acute lymphoblastic leukemia ALL and primary plasma cell leukemia pPCL, myelodysplastic syndromes, renal cell carcinoma) and studies of gut microbiome in human health and disease ( Down syndrome, Behcet syndrome, graft-versus-host disease GVHD) as well as studies on mechanisms of infection of B. Pseudomallei and secondary metabolism regulation in antibiotic producing actinomycetes

Proteomics Unit has performed the development of innovative methodologies for investigating both metabolome and proteome. Specifically, this unit has improved an an original pipeline based on MudPIT approach and computational tools, including label-free quantitation, clustering and network analyses, allowing the study of a wide range of actual sample, such as cell lines, fluids and tissues, fresh, frozen and paraffined. In addition, LC-MS analysis has been used for characterizing lipid profiles of tissues. The developed expertises and facilities has been used to perform studies concerning biomarker/target discovery in a wide range of diseases, such as cardiovascular, neurodegenerative, oncological, metabolic and respiratory ones, in collaboration with national and international groups.
The activities of Proteomics Unit have permitted to obtained important results in the context of molecular profiles. Firstly, this Unit demostrated that MudPIT approach is a good starting point to translate proteomics to clinical applications. In addition, characterization of protein profiles of exosomes from urine and neuroblastoma cellular lines evidenced the important information contained. Clinical applications of MudPIT approach concern cardiovascular and neurodegenerative diseases for evidencing both the metabolic pathways involved and specific proteins, such as MHC-I in Parkinson disease, and the efficacy of drug and stem cell therapy, such as in heart failure. Of note, it was possible to develop unbiased diagnostic methods for systemic amyloidosis and the proteomic state of bronchial tissues for predicting the responsiveness of anti-IgE treatment for asthma severe. Also, important results were obtained about oocyte fertilization, tumor protein profiles and bacterial membrane.

The Bioinformatics and Translational Bioinformatics Unit is involved produces high throughput genotyping data to be analyzed by bioinformatics tools and validates different bioinformatics predictions. It is particularly involved in understand the gene-environment interactions in neurodevelopmental disorders and in developing new diagnostic protocols for lymph node metastasis. The unit aims to develop an integrated platform for the management and execution of bioinformatics protocols with particular reference to drug design and the annotation of biological sequences.
The Bioinformatics and Translational Bioinformatics Unit has found SNPs correlating with autism, has validated lists of microRNAs obtained by bioinformatics predictions and has found molecular markers of a cardiomyopathy in veterinary field. Molecular mechanisms of HIV-1 matrix protein p17 variants in promoting tumorigenesis and neurodegeneration. Development and application of modeling techniques in the filelds of protein-ligand interactions for the rational drug design of Cystic Fibrosis therapy, phosphodiesterase (PDE), viral protein and protein C involved in the regulation of blood coagulation.

The activities of Neurochemistry laboratory (Aging and neurodegenerative disease) focus on the study of mechanisms of brain aging. Particularly, the laboratory is studying by a multi-analytical approach specific subcellular organelles containing neuromelanin, lipids and proteins, which accumulate inside neurons during normal aging. These organelles largely accumulate in dopamine neurons of the substantia nigra and norepinephrine neurons of locus coeruleus, the main brain areas that undergo severe degeneration during Parkinson's disease.
The activity of the Neurochemistry laboratory (Aging and neurodegenerative disease) over the last few years has resulted in a complete molecular characterization of neuromelanin-containing organelles of the human substantia nigra, thus identifying them as atypical lysosomes derived from an autophagic pathway and with a reduced enzymatic activity. During this fine molecular characterization, we have recently confirmed the presence of an important protein involved in antigen presentation, notably the MHC-I. This finding is able to explain the selective vulnerability of dopamine neurons of substantia nigra and norepinephrine neurons of locus coeruleus, shedding the light on immunologically-based mechanisms of neuronal death and chronic inflammation typically underlying Parkinson's disease.

The activities of the Clinical Epidemiology of Neurodegenerative diseases laboratory are focused on the study of the relationship between cancer and neurodegenerative diseases, specifically Alzheimer's and Parkinson's diseases, to better understand the mechanisms underlying senescence and aging in relation with neoplastic growth and neurodegenerative processes.
The laboratory is also involved in the evaluation of the association between diet and other lifestyle related factors in adulthood and the occurrence of dementia in old age.
The research group has taken part in European and national projects that, through the ICT (Information and Communication Technology) are aimed to promote healthy lifestyles in both elderly and young people.
The study of the relationship of occurrence between cancer and neurodegeneration confirms the evidence that subjects with cancer have a low incidence of neurodegenerative disorders and vice versa, and suggests that this inverse relationship is not explained by different distributions of modifiable risk factors, supporting the hypothesis of a biological role in this relationship.
The study of association between dietary habits and dementia highlights that an elevated intake of fats, in particular of the É3 fatty acids, is inversely associated with the risk of developing incident dementia independently from other potential confounders.

The Stem Cell and Cancer Stem Cell Unit is committed in studying the processes associated with cell reprogramming for a better understanding of the mechanisms of conversion of normal stem cells into cancer stem cells. Research is focused on the identification of epigenomic signals and chromatin remodeling factors that determine the cell- and the stem cell- identity and tissue-cell specific function, and factors that prevent genomic instability, tumorigenesis and cancer progression. Regulation of mRNA stability, splicing and translation and how epigenomic signals influence chemo-resistance in cancer cells are also actively being investigated, using human stem cells and cancer stem cells, induced pluripotent cells (iPS) and reconstituted human 3D (3 dimensional) tissue models.
Using a Cancer Stem Cell Model we identified 11 gene exclusively expressed Cancer Stem Cells that may define a cancer stem cell signature. We also identified micro-RNAs and novel transcripts having a role in tumor invasion, in epithelial to mesenchyme transition (EMT), in the regulation of Cancer Stem Cell self-renewal and in cellular reprogramming of human iPSCs.


Branch Research Center - Bari:

The research activities in Functional Genomics were based to identify molecular biomarkers. A line of research investigates the role of the tumour suppressor p53 family members in cellular proliferation in physiological and pathological processes . Recently, we have identified a new positive modulator of the stability and activity of p53, called TRIM8, which has been found down-regulated in chemo resistant cancers. Another research line investigates the role of small non-coding RNAs inside of the human hormone regulated cancers such as thyroid cancer and ovarian cancer. This research line has produced a Patent (RM2010A000293- PCT/IB2011/052369). The last paper on "TRIM8 anti-proliferative action against chemo-resistant renal cell carcinoma.", has been tagged as Higly accessed and have been especially highly accessed, relative to their age, and the journal in which they were published.

The Bioinformatics research line focuses on the development of innovative Bioinformatic tools for the management, analysis and interpretation of the large amount of data produced by means Next Generation Sequencing (NGS) technologies. Research line is orientated in the development of a computational framework to study the role of the small non-coding RNAs, such as, microRNAs involved in various biological processes by negatively regulating gene expression. Another field of the research is Biodiversity Informatics within LifeWatch iniziative. This research line has received
In the last year funding from European Commission, and National MIUR-PON (MICROMAP, VIRTUALAB).

The research activities in Neurodegenerative Diseases focuses in developing an integrated multi-disciplinary approach of Clinical, Neuroradiological and Molecular Data using a High-performance Next-Generation Sequencing (NGS) Technologies for measuring circulating microRNA (miRNA) expression and their target genes, in order to shed light in some neurodegenerative disorders of interest like Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS). This research line has received recently an funding from Italian Federation of Multiple Sclerosis (FISM) for to study cognitive impairment in Pediatric Multiple Sclerosis: searching for biomarkers predictive of progression.


Research Unit - Pisa:

The ITB Research Unit in Pisa investigates molecular mechanisms regulating adult stem cells, which contribute, once dysregulated, to tumor development and progression. One of our research interest aims at characterizing mesenchymal stem cells (MSCs) and the role that HOX, TALE and OTX homeobox-transcription factors play in their regulation. Another research line we are pursuing deals with the identification and characterization of molecular pathways involved in pulmonary tumorigensis and leukemogenesis, ultimately leading to identify and test targeted therapies.
These are our recent results/accomplishments:
i. MSCs derived from different body sites have different proliferative and differentiative ability, and specific molecular signatures. Therefore they do not represent equivalent cell sources for regenerative medicine applications.
ii. A consistent percentage of pulmonary adenocarcinomas is characterized by low expression of the tumor suppressor C/EBPa and a concomitant high expression of the oncogene Bmi1. The same inverse correlation between C/EBPa and Bmi1 is mimicked in the lung cancer murine model we generated.
iii. Treatment of human and murine lung cancer cell lines with a novel antiBmi1 compound revealed that upon Bmi1 inhibition tumor growth is significantly decreased. Our data contributed to a new clinical trial recently started in USA.



Branch Research Center - Roma:

The Research Unit of Rome carries out research in the fields of bioethics and biopolitics, with particular reference to biolaw and human rights, as well as to research ethics, which also encompassed the emerging sector of Research Integrity. The latter analyzes the principles, the rules and the values that regulate the conduct of scientific research at domestic and at international level. Specific research lines are devoted to medical ethics (in particular to 'Rare neglected and poverty related diseases') and to neuroethics. A particular research topic investigates the decision making process, the role of lobbies and involvement instruments concerning the formulation of collective decisions regarding the most important subjects of interest for the Institute. The research methodology is based upon a multidisciplinary approach, that integrates knowledge and skills of social sciences with those of the biomedical sector and more in general of natural sciences. The research unit has a role of technical and scientific support to the CNR Commission for Research Ethics and Bioethics.
The Research Unit of Rome has been established in September 2013. Its main results concern: scientific support to the CNR Commission for Research Ethics and Bioethics, included the formulation of several opinions and the drafting of the first ever adopted Italian Guidelines on Research Integrity (to be published in June 2016); the management of research projects in the field of "Rare, neglected and poverty related diseases" (financed by the CNCCS Consortium) and of "Neuroethics and Justice Administration" as coordinator (financed by the MIUR); a huge amount of publications in several sectors of interest. The bilateral scientific cooperation at international level is wide. Two agreements of scientific and technical cooperation- comporting the acquisition of financial resources - have been signed with the Sapienza University of Rome and with the Umberto Veronesi Foundation. Several researchers of the Unit have teaching assignments at national and international universities. The head of the Unit, Cinzia Caporale, is member of prestigious Italian ethics committees and represents CNR and/or Italy at international fora.