Research
Making research at DSFS
The main research groups working within DSFS are organized in six sections: Biochemistry, Chemistry, Medicinal Chemistry, Pharmaceutical Technology, Pharmacology and Toxicology, Systems Biology.
Biochemistry section
Research is primarily focused on apoptotic processes, role of TG-2 in cellular differentiation, mechanism of action of NOS activators and inhibitors and the potential therapeutic application of stem cell.
Chemistry section
Organic synthetic methodologies regarding asymmetric 1,3-dipolar cycloaddition reactions and carbohydrates, synthesis and structural characterization of polyhydroxyalkanoates. Study of physical, chemical and structural properties of materials and Smart Molecular Constructs Activated by Light, including their pharmaceutical and industrial application.
Medicinal Chemistry section
Primary research targets are design, synthesis and development of neuroprotective, anxiolytic, analgesic and anticancer agents utilizing the most advanced techniques such as as MM and ADME.
Pharmaceutical Technology section
Development of new drug delivery systems (DDS) for pharmaceutical, cosmetic/cosmeceutical, nutraceutical/food applications, using several techniques such as percutaneous absorption and non-viral vector studies. Calorimetric studies are performed by DSC.
Pharmacology and Toxicology section
Research is focused on two major fields of interest: neurophamacological and neurobiological studies with a special attention to Alzheimer’s disease and neuromodulation of pain transmission and mnemonic processes.
MEET THE YOUNG RESEARCHERS OF DSFS
Department researchers carry out basic and applied (pre-industrial) research activities in the different fields of competence, mainly supported by private and public funding, from both national and EU origin.
The main research lines upon which the current activities are focused are:
i) naturally occurring biologically active compounds (pharma, nutraceuticals, food, cosmetics);
ii) neurosciences (drug design & development, brain drug delivery, neurobiology, neuropharmacology);
iii) chemotherapeutics (antibacterials, antifungals, antivirals, anticancer agents);
iv) modeling and simulation of biological systems (in silico medicine, in silico clinical trials, prediction of efficacy and safety of medicinal products, in silico drug discovery).
To date, 20 researchers from DSFS are cited in the AD Scientific Index 2023 (https://www.adscientificindex.com/top-100-scientist/?con=Europe)
Among the main current research projects:
HEALTH COESION PLAN - Driver no. 4 (Biotechnology, bioinformatics & pharmaceutical development)
Title: PHARMA-Hub
Topic: Drug repurposing in paediatric neurological rare diseases
Pilot Project (case study): Ataxia-telangiectasia (Louis-Bar Syndrome): it is a rare neurodegenerative disease, which generally begins in childhood and causes serious disability. The prognosis is serious, due to the possibility of the onset of immunosuppression, respiratory infections, neurodegeneration, ocular and skin telangiectasias, and the risk of developing tumors.
The activities that will be carried out by DSFS researchers range from the use of databases (e.g. FDA, EMA) of drugs and pharmacological tools to be evaluated in silico regarding their fit with the signaling pathways of the different clinical forms of (rare) diseases to be studied, to the biochemical and pharmacological characterization of the relative mechanisms of action and preclinical activity, to the (re)formulation of pharmaceutical forms suitable for pediatric use and personalized therapies (drug repurposing).
The objective that is intended to be achieved over the 4 years of the project is to channel the results of research activities by converting them, through therapeutic repositioning strategies of drugs, into the development of new therapies, industrially scalable, for the clinical treatment of rare neurological diseases in pediatric field.
NEXT GENERATION EU: THE RESEARCH PROJECTS
Many DSFS researchers participate to project financed by PNRR funds
(https://www.unict.it/it/ricerca/piano-nazionale-di-ripresa-e-resilienza-pnrr)
PE6 - PARTNERIATO ESTESO SULLA MEDICINA DI PRECISIONE
Project: HEAL ITALIA - Health Extended ALliance for Innovative Therapies, Advanced Lab-research, and Integrated Approaches of Precision Medicine
- Proff. Rosario Pignatello, Teresa Musumeci, Angela Bonaccorso
Challenge:
The metabolic syndrome, which includes diabetes and obesity, one of the most widespread medical conditions, induces brain disfunction and has been also related to neurodegenerative diseases. Licensed medicines are mostly given by oral administration and are limited by the difficulty in crossing the blood–brain barrier (BBB). The nasal route has been explored as an alternative pathway that allows drugs to be directly delivered to the brain via the nasal cavity. However, clearance mechanisms in the nasal cavity impair the delivery of drugs to the brain and limit their bioavailability. Nanomedicine have been proposed as strategy for nose-to-brain delivery to overcome the limits due to site of administration and facilitate drug transport directly to the brain, minimizing side effects and maximizing therapeutic benefits.
Research:
The aim of the project is the design and production through a Quality-by-Design (QbD) of different nanocarriers loaded with small drug molecules, peptides or proteins, planned to bypass the blood brain barrier using the intranasal route. The selected suitable nanocarriers will be tested in vivo to prove their higher efficacy compared to free drugs and/or to different routes of administration (IV or oral).
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Prof. Antonio Rescifina
This project aims to accelerate the exploitation of a kit-based THP technology for the production of PET tracers for the detection of cancer and other human pathologies using the advantages of 68Ga. Differently to the nowadays used PET tracers, the products derived from the development of the project will have the advantages of using THP as chelating unit for the 68Ga. This will ensure a quantitative radiolabelling in extreme mild conditions without eluate pre-processing or post-labelling purification. Moreover, other radionuclides, such as In111 and Ga67, and others, can be quantitatively labeled with the same products ensuring other applications in detection and therapy.
- Proff. Salvatore Sortino, Aurore Fraix
Challenge:
The use of photo-generated non-conventional agents (NO, 1O2 and heat) required the development of highly efficient, non-toxic precursors able to be to stimulated by biocompatible light. Then, the precursors need to be formulated for efficient delivery to the tumour. This formulation step is not trivial as it is not obvious that chromophores preserve their properties when they are confined in a restricted area. This became even more challenging if conventional drugs are added to the formulation.
Research:
The aim of this research is the design, fabrication and characterization of light-activatable molecular and supramolecular systems or nanomaterials able to release non-conventional therapeutic species (nitric oxide (NO), singlet oxygen (1O2) and heat) in order to overcome MDR phenomena in cancer cells. Successively these systems will be associated with conventional chemotherapeutic to take advantage of additive or synergistic effect. When possible, the therapeutic properties will be associated with fluorescent properties, desirable for the imaging.
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CN1 - Centro Nazionale per simulazioni, calcolo e analisi dei dati ad alte prestazioni
- Proff. Francesco Pappalardo, Giuseppe Forte, Salvatore Guccione, Antonio Rescifina, Simone Ronsisvalle
Spoke 8 will carry out two major activities, i) In Silico Medicine & ii) Omics Data.
In silico medicine aims at the following objectives:
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To develop a fully integrated digital data flow between the HPC center and the healthcare centers.
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To use HPC solvers to develop vertical solutions for In Silico Medicine (both Digital Patient and In Silico Trials, which provide sufficiently large-scale or the necessary computational performance)
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To expose these solutions through automated pipelines that hide the complexity to clinical and industrial end-users and allow automated workflows that execute and return into the Electronic Health Record of biomarkers predicted in silico as soon as the necessary input data are made available for that patient.
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To conduct comparative studies on selected in silico medicine applications to quantify the performance and cost benefits of using an advanced HPC platforms and not medium-range clusters or cloud computing.
Omics data aims at the following objectives:
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To design and develop a fully automatized workflow, in which all the steps can benefit from ad hoc software, graphical interfaces (i.e., LIMS), etc.
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To deploy bioinformatics pipelines capable of performing exceptionally on next-generation hardware, including GPU-based HPC or FPGA.
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To develop machine learning algorithms (including machine vision) to analyze omics data (including radiomics) efficiently, with the final goal to provide reliable correlations and associations.
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To stratify patients for improved diagnoses and more efficacious pharmacological treatments.
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To calculate thermodynamics and kinetics of drug-target binding through HPC-optimized physics-based methods (portability to quantum computing will also be investigated).
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To deploy user-friendly and ready-to-use software packages for the medical and biological community country-wise.
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Centro Nazionale di Ricerca 3 – Sviluppo Di Terapia Genica e Farmaci con Tecnologia a RNA (spoke 2)
- Dr.ssa Agata Grazia D'Amico
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Ecosistemi dell’Innovazione “Micro and nano technologies and systems for energy, environment, smart agriculture, smart mobility, health and cultural heritage
PROGRAMMA: SAMOTHRACE - SiciliAn MicronanOTecH Research And Innovation CEnter
- Proff. Filippo Caraci, Salvatore Petralia
ITM3) Development of nanostructured materials and integration on microfluidics systems for liquid biopsy application.
- Prof. Giuseppe Forte
Environment: 2D materials to mitigate the environmental impact of electronic waste.
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ECOSISTEMA INNOVATIVO DELLA SALUTE
Progetto: Life Science TTO Network (PerfeTTO)
Prof. Pierfrancesco Veroux (Dipartimento CHIRMED) e prof. Filippo Caraci
Abstract: the project involves 55 Italian Spokes representing the majority of IP/TT offices belonging to health care institutes and scientific institutions. The main project objectives are: establishing and consolidating a nationwide open and sustainable Technology Transfer Office (TTO) Network, which will connect, coordinate and align Network Partners and stakeholders (Research and Care Institutes (IRCCS), Universities, National Health System, Investors, SMEs, Industry, National and International Consortia) as well offer world-class services in a synergistic valuable way at national and international level.
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Piano Complementare PNRR – linea 1a
PROGRAM: ANTHEM - AdvaNced Technologies for Human-centrEd Medicine
Topic 4) Therapeutic solutions for orphan diseases
- Prof.ssa Claudia Di Giacomo
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VALORIZZAZIONE E POTENZIAMENTO DELLA RICERCA BIOMEDICA DEL SSN
Project: Theranostics in gastric cancer through immunotargeting of the CSPG4 cell surface proteoglycan
- Prof. Giuseppe Floresta
RESEARCH PROJECTS WITH HORIZON EUROPE / HORIZON 2020 CALLS
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines (ERAMET).
PI: Prof. Francesco Pappalardo
Starting date: 1/1/2024. Horizon Europe call. Description: ERAMET will provide an integrated approach for developers and regulators’ decision-making for paediatric and orphan drugs, centred on the drug development questions. This will constitute a transparent ecosystem for drug development and assessment, that will facilitate the adoption of modelling and simulation (M&S) methods and related data types (including real word data such as registries and electronic healthcare data). The overall objective of ERAMET is to provide and implement a framework for establishing the credibility of M&S methods and related results as sources of evidence within regulatory procedures. The ecosystem proposed by ERAMET will be based on three pillars: (1) A repository connecting questions, data and methods. (2) The development and validation of high-quality standards for data and analytical methods (including M&S and hybrid approaches). These will cover computational M&S, digital twins, AI, hybrid approaches, standard statistics and pharmacometrics, as analytical methods and alternative data types and sources such as RWD, eHealth data, registries, historical regulatory submissions, scientific and (non)clinical trials). (3) An AI-based platform that will automate and optimise the data collection, formatting and modelling and simulation analysis and implement the credibility assessment. As part of ERAMET, the ecosystem will be applied to five use-cases including paediatric extrapolation and characterisation of drug benefit/risk in 4 groups of rare diseases, namely ataxia, transfusion dependent haemoglobinopathies, bronchopulmonary dysplasia, and degenerative neuromuscular. Each of the use-case is planned to lead to submission and regulatory approval of at least one validated M&S tool via the EMA qualification procedure. Training will be proposed to familiarise regulatory assessors, drug developers and clinical researchers with this new approach.
Novel immunotherapies for tuberculosis and other mycobacterial diseases (ITHEMYC).
PI: Prof. Francesco Pappalardo
Starting date: 1/6/2023. Horizon Europe call. Description: Tuberculosis (TB) remains the leading cause of death due to a single pathogen, Mycobacterium tuberculosis (Mtb; except in 2020-2022, when it was surpassed by the COVID-19 pandemic), with 1.5 million deaths in 2020. The lengthy TB treatment and the numerous adverse events contribute to poor medical adherence and development of antibiotic resistant strains. Thus, novel therapeutic modalities are urgently needed to shorten treatment duration, improve outcomes and control the emergence of drug resistant TB. The ITHEMYC project convenes a multidisciplinary consortium of 11 partners, including two Product Development Partnerships (TBVI, TB-Alliance) and an industrial partner (GSK) involved in vaccine, drug and biomarker R&D for TB. The partners will work jointly to develop innovative adjunctive TB immunotherapies by capitalizing on a promising pipeline and recent developments in the field. The project will combine current and new antibiotic regimens with novel immunotherapies, such as small molecules targeting host pathogen-interactions, including host-directed therapies and virulence inhibitors, immunomodulatory compounds, monoclonal antibodies and therapeutic vaccines. The project will generate robust preclinical safety and efficacy information on compounds and combinations through a set of relevant in vitro, in vivo and in silico models, and progress two of them up to preclinical proof-of-concept in non-human primates within the project duration. The partners are proposing a critical path for characterization and progression of immunotherapies, that will be refined based on knowledge generated in ITHEMYC aiming to increase the understanding and interest for this emerging concept of adjunctive TB immunotherapy. We expect the new combined interventions will improve TB cure rates, reduce the duration and toxicity of current regimens and reduce relapse rates.
In Silico World: Lowering barriers to ubiquitous adoption of In Silico Trials (ISW).
PI: Prof. Francesco Pappalardo
Starting date: 1/1/2021. Horizon 2020 call. Description: Computer models informed by experimental data enable us to test hypotheses and make predictions, significantly streamlining the research and development cycle relative to trial and error. When it comes to medicine, experimentation relies on biological samples ranging from cultured cells to whole animals, so increased reliance on modelling has additional benefits. Harnessing Big Data and tremendous advances in computing power could pave the way to minimising and eventually eliminating the need for anything other than in silico 'experimentation' in medical research and development. The EU-funded ISW project will bring together a large European consortium and a multi-stakeholder advisory board to lay the groundwork to achieve this goal with attention to the models, regulation, standardisation and more.
Identification of the Molecular Mechanisms of non-response to Treatments, Relapses and Remission in Autoimmune, Inflammatory, and Allergic Conditions (3TR).
PI: Prof. Francesco Pappalardo
Starting date: 1/9/2019. IMI2 Horizon 2020 call. Description: The identification of the molecular mechanisms that can positively or negatively influence a patient’s response to medical treatment is a key issue among health practitioners. A study promoted by 3TR, a consortium of university institutions, SMEs and leading pharmaceutical companies, will address this issue. This EU-funded project will apply bioinformatics and control methods to collect and analyse data from blood, tissues and other fluids during the entire treatment process. It will create a centralised data platform for better management and implement an inclusive molecular and clinical picture of patients experiencing similar diseases. The project intends to explain the role that our microbiome, genetics and regulatory genomics play during treatment.
SUPREME - Polymeric Cyclodextrin-Based Supramolecular Constructs Photoreleasing Nitric Oxide for Combating Antibiotic Resistance
Resp. scientifico: Prof. Salvatore Sortino
Summary: SUPREME aims at the implementation of a novel strategy based on supramolecular platforms based on new cyclodextrin polymers integrating light-activatable nitric oxide (NO) photodonors (NOPD), alone and in combination with conventional antibiotics currently employed in the clinic. The final goal is to exploit the role of NO generated with precise spatiotemporal control to revert antibiotic resistance through different mechanisms of action.
CLOSED PROJECTS:
In Silico Trial for Tuberculosis Vaccine Development (STriTuVaD).
PI: Prof. Francesco Pappalardo
Starting date: 1/2/2018. End date: 31/01/2023. Horizon 2020 call. Description: Tuberculosis (TB) one of the world’s deadliest diseases: one third of the world’s population, mostly in developing countries, is infected with TB. But TB is becoming again very dangerous also for developed countries, due to the increased mobility of the world population, and the appearance of several new bacterial strains that are multi-drug resistant (MDR). There is now a growing awareness that TB can be effectively fought only working globally, starting from countries like India, where the infection is endemic. Once a person present the active disease, the most critical issue is the current duration of the therapy, because of the high costs it involved, the increased chances of non-compliance (which increase the probability of developing an MDR strain), and the time the patient is still infectious to others. One exciting possibility to shorten the duration of the therapy are new host-reaction therapies (HRT) as a coadjuvant of the antibiotic therapy. The endpoints in the clinical trials for HRTs are time to inactivation, and incidence of recurrence. While for the first it is in some cases possible to have a statistically powered evidence for efficacy in a phase II clinical trial, recurrence almost always require a phase III clinical trial with thousands of patients involved, and huge costs. In the STriTuVaD project we will extend our Universal Immune System Simulator to include all relevant determinants of such clinical trial, establish its predictive accuracy against the individual patients recruited in the trial, use it to generate virtual patients and predict their response to the HRT being tested, and combine them to the observations made on physical patients using a new in silico-augmented clinical trial approach that uses a Bayesian adaptive design. This approach, where found effective could drastically reduce the cost of innovation in this critical sector of public healthcare.
PRIN 2022 RESEARCH PROJECTS (2023-2025)
(Funded by European Union – Next Generation EU )
- Harnessing the potential of the THP: moving toward the development of a clinical-grade kit for a peptide-based PET imaging agent for real-time imaging and treatment of aberrant c-Met cancers for another giant step in cancer treatment - dr. Giuseppe Floresta (P.I.).
- Tackling neurodegeneration with by-product-based-nanohydrogels for the nose-to-brain-delivery of natural bioactive compounds (TANDEM) - prof.ssa Teresa Musumeci; PI: P. Di Martino (Univ. di Camerino).
- Development of broad-spectrum coronavirus antiviral agents acting as allosteric modulators of the host protein sigma-1 - prof. Agostino Marrazzo; PI: G.P. Mangiatordi, Institute of Crystallography (CNR-IC).
- “Running away” from PTSD: from mechanisms of vulnerability towards innovative combined therapies - prof. Filippo Caraci; PI: P. Campolongo, Università degli Studi di ROMA "La Sapienza".
- Future challenges in management of recurrent/resistant Infection: development of antimicrobial Nanoparticulate systems and physical-chemical investigation of their Interactions with biofilm-associated infection (FINI) - prof. V. Pistarà; PI: V. Venuti, Univ. di Messina.
- In silico-design, synthesis and characterization of innovative two components Light-absorber (LA)-G-quadruplex (G4) binder conjugates: a new paradigm to afford a dual anti-cancer approach (LA-G4-DACA) - Prof.ssa Aurore Fraix; PI: M.E. Alberto, Univ. della Calabria.
- Dissecting the mechanisms associated with cognitive deficits in Alzheimer’s disease: the GAT3 connection - prof.ssa Agata G. Copani; PI: S. Oddo, Università di Messina.
- Revealing the Impaired MEchanisms underneath aspirin low-responder patients with DIabetes mellitus (RIMEDI) - Prof. Luca Vanella; P.I.: F. Santilli, Università degli Studi "G. d'Annunzio" Chieti-Pescara.
- Reconfigurable Low-Dimensional Nano-Structures at Liquid Interfaces (ReLoDS) - Prof. Francesco Punzo; P.I.: G.C. Li Destri Nicosia, Università di Catania.
- Supramolecular catalysis in self-organized nanocontainers (CAGED) - prof. Antonio Rescifina; PI: C. Talotta, Univ. di Salerno.
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Investigation of Tau- dependent epigenetic reprogramming in Alzheimer’s disease - prof.ssa Lorella Pasquinucci (PI: prof. F. Basolo, Univ. of Pisa)
PRIN-PNRR RESEARCH PROJECTS (2023-2025)
(Funded by European Union – Next Generation EU)
- Innovative formulations for the treatment of recalcitrant infections of the ocular surface (NANOEYE) - Prof. Rosario Pignatello (PI), in collab. con le Università di Messina e di Salerno.
- Identifying the role of a natural dominant-negative variant of DNA polymerase-β on the onset and progression of Alzheimer’s disease - Prof.ssa Agata C. Copani
- Novel biomedical devices combining antimicrobial and anti-inflammatory activity by embedding bioactive-loaded nanoconstructs in polymer films for more effectiveness in infectious disease treatment (BIONANOF) - Prof. Salvatore Petralia; PI: Prof. P. BERNARDO (CNR, Rende)
- A Double Hybrids strategy for cancer treatment by targeting the Heme Oxygenase system (HO-Hybrid2) - Dr. Sebastiano Intagliata (PI), in collaboration with CNR-ISMN of Messina (M. Trapani) and Università degli Studi di Napoli Federico II (E. Magli).
- A molecular platform for intracellular nitric oxide sensing. - Prof. Salvatore Sortino, in collab. con l'Università di Parma
- Biomass-derived sensors for the detection of heavy metals in water (BioMetSensor) - Prof.ssa Maria Assunta Chiacchio - in collaboration with University of Messina
- Role of second-generation antidepressants in Traumatic Brain Injury: focus on TGF-beta1 pathway and the gut/brain axis - Prof. Filippo Caraci (P.I.)
- Utilizzo dei sottoprodotti di Cynara spp. come fonte di molecole con attività inibitoria sugli enzimi cutanei. - Prof. Venerando Pistarà, in collab. con le Università di Cagliari e Napoli Federico II e il CNR-ISMN di Messina.
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BIOmass VAlorization by NAturally-derived MAcrocyclic Deep Eutectic Solvents (BioVaNaMADES) - Prof. Antonio Rescifina, in collab. con l'Università della Calabria.
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Green Protein-Based Nanohybrids as Adaptive Surfactants” (GrASs) - Prof. Francesco Punzo (PI: prof. G.C. Li Destri Nicosia, UniCT).
DECARB - Processi avanzati di decarbonizzazione e valorizzazione della CO2 nell’ambito del settore della produzione del cemento (Advanced processes of decarbonization and valorization of CO2 in the cement production sector)
In collaboration with UniCT (Prof. A. Rescifina) and TeamNetwork srl
ICOD an EU Project in collaboration with IRCCS Oasi di Troina
21 marzo 2021 - Important success for the prof. Filippo Caraci, professor of Pharmacology of the Department of Pharmaceutical and Health Sciences and head of the Neuropharmacology UOR at the Oasi di Troina, coordinator for the dissemination activities at European level of the ICOD project, aimed at testing the first drug of a new pharmacological class, AEF0217, directed towards the cannabinoid receptor (CB1) in the treatment of cognitive deficits in Down syndrome.
Miglioramento della Competitività e Sostenibilità delle Filiere mediterranee agroalimentari attraverso il Recupero di Scarti e Sottoprodotti, la Tutela della Biodiversità e lo Sviluppo di nuovi Prodotti
(Improving the Competitiveness and Sustainability of Mediterranean agri-food supply chains through the recovery of waste and by-products, the protection of biodiversity and the development of new products)
The project, coordinated by prof. Salvatore Petralia, aims at the creation of a portable Point-of-Care (PoC) demonstrator for monitoring phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA) and at demonstrating its functionality in a real operating environment.
