(Prof. Lucia Altucci, Prof. Michele Caraglia)

Oncology and Precision Medicine (Prof. Michele Caraglia)

The Molecular and Precision Oncology laboratory, coordinated by Prof. Michele Caraglia and managed by Dr. Marianna Scrima, focuses on the characterization of circulating miRNA signatures, with the aim of proposing new diagnostic and therapeutic approaches. The main goal is to determine a circulating miRNA signature with innovative nanosensors, for the diagnostic and prognostic determination of squamous cell carcinoma of the larynx and more generally of the tumors of the head and neck area. This new technology will be applicable for any other neoplasia of which there are known circulating miRNA signatures to be determined in real time in the patients' blood through a nanotechnological device easy-to-use directly at the point of care (i.e., the patient's bed), without the need for complicated laboratory procedures. The biological role of these miRNAs in human cancers is also studied in order to identify new therapeutic strategies, based on the regulation of miRNA expression in cancer cells, through the use of nanotechnological approaches. The laboratory is also able to perform genotypic characterization in next generation sequencing (NGS) of human cancers, such as colorectal, breast, bladder, lung and hepatocellular carcinoma. These molecular features are useful for understanding the biological mechanisms that guide their development and determine their response to treatments.

The laboratory is also working to the characterization of gene expression of individual tumor cells, through single cell (nuclei) RNA sequencing techniques (with reference to squamous cell tumors of the head and neck district), and to the determination of the prognostic and predictive impact of responses of individual cellular genetic signatures. This project will allow us to identify new tumor-specific markers that can be useful for diagnostic and prognostic definition and for the identification of the component in the tumor microenvironment that influences the clinical course of the neoplasm. This information is important also for predicting the response of patients to immunotherapy and for identifying new therapeutic targets. These studies are supported by the characterization of the gene expression of the neoplasm from paraffin-embedded tissues of the same patients and of a cohort of patients along with all the clinical and pathological information. (Dr. Federica Melisi, Dr. Alessia Maria Cossu, Dr. Marco Bocchetti).

Another project is currently in progress, in collaboration with the Biogem Computational Biology laboratory. This project aims to identify the fragmented circulating tumor DNA and the methylation of regions of circulating tumor DNA from plasma of patients affected by various neoplasms (colon, breast, melanoma, lung, head and neck tumors, bladder) in order to determine signatures capable of early diagnosis of cancer and of predicting survival and response to treatments. The design of a bioinformatics algorithm will make possible to predict the presence of the neoplasm, the primary tissue of origin and the prognostic characteristics.

Finally, in collaboration with the Biogem Translational Nephrology laboratory, there is a project in progress about the characterization of circulating miRNAs in the serum of renal transplant patients who develop post-transplant neoplasms, with the aim of identifying a predictive signature (Dr. Piera Grisolia, Dr. Cinzia Graziano, Dr. Clara Iannarone).

Other projects presently in progress:

- Study of the effects of hypoxia on the genotypic and epigenetic characteristics of human mesothelioma (Dr. Marco Bocchetti, Dr. Cinzia Graziano).

- Genotypic characterization of thin melanoma: impact on prognosis and response prediction (Dr. Federica Melisi, Dr. Lucia Pasquale).

- Study of the cross-talk between micro-RNA and long non coding RNA in human hepatocellular carcinoma (Dr. Marco Bocchetti).

- Characterization of the effects of radiotherapy on gene expression in glioblastoma cells (Dr. Federica Melisi, Dr. Lucia Pasquale).

- Study of the genetic susceptibility to neoplastic cachexia (Dr. Lucia Pasquale).

- Study of genetic and epigenetic susceptibility to SARS-Cov-2 infection (Dr. Alessia Maria Cossu, Dr. Clara Iannarone).

Technologies used / developed

The Molecular and Precision Oncology laboratory is equipped with technology for molecular and cell biology. In particular, it has clean rooms for cell cultures with safety devices for the manipulation of viral strains; a confocal microscope in white light and fluorescence, equipped with a CCD camera, FACS; equipment for gene sequencing of Next Generation Sequencing (PGM, Ion GeneStudio™ S5 System, Illumina Next 550), QuantStudio 7 Flex Real-Time; RT-PCR equipment (Pyromax and Therascreen); FACS cell sorter BD for the isolation and collection of single cells, based on their phenotypic characteristics.

Services offered

The laboratory aims to offer the genotypic characterization of colorectal and breast carcinomas of samples from patients affected by these diseases, in order to develop a collaborative network between the main universities and hospitals in Campania region. Thanks to a bioinformatics tool that optimizes and simplifies the annotation of sequence data, the analysis obtained by evaluating quality score and frequency parameters would allow for the development of a personalized medicine. In this way, therapeutic treatments could be developed based on the characteristics of each patient, with the right combination of drugs (based on each patient’s genetic profile and the profile of the disease) with the appropriate dose and at the right time.

Epigenetica

(Prof.ssa Lucia Altucci e Prof. Vincenzo Carafa)

The medical epigenetics group studies the role of epigenomic alterations and epigenetic modifications, also at the single cell level, in human pathologies, with a focus on leukemia and solid tumors, degenerative, cardiovascular and metabolic pathologies. The identification of epigenetic biomarkers allows for the development new therapeutic targets and diagnostic and prognostic targets. Our group aims at translational activities, including the identification and characterization of epimutations, and the development of diagnostic and prognostic methods for identifying the disease and the response to treatments. The group also focuses on drug discovery activities, to identify and characterize innovative treatments based on the use of new molecules that target chromatin.

SPECIFIC LINES OF RESEARCH

1. Characterization of the role of sirtuins (and modulators) in human development and pathologies.

2. Identification and characterization of the role of class B acetyltransferases in tumors.

3. Characterization of epigenomic alterations in leukemias with bioinformatics methods

4. Characterization of epigenomic alterations in colorectal cancer, with bioinformatics methods

5. Identification and characterization of the role of micro-vesicles in cell communication and in human pathologies, such as tumors.

6. Use of alterations in metabolic pathways for the development of innovative therapeutic strategies.

7. Innovative epigenetic approaches for the identification of therapeutic strategies against SARS-Cov-2.