Developing proprietary fluorescent probes targeting high grade gliomas into useful tools for onco-surgery and theranostic

• Research Director: Prof. Silvia Garavaglia 
• Call: Proof of concept (PoC)
• The two-year project has acquired funding of 170,000 euro.

The project aims to develop fluorescent inhibitors, already patented, which selectively identify human tumour stem cells expressing ALDH1A3. These inhibitors bind to ALDH1A3 and identify positive tumour cells, both in vitro and in vivo. Goals include expansion of in vivo testing, designing new fluorescent substrates targeting ALDH1A3 and other ALDH1A family members, and complexation of the compounds with gadolinium for neutron capture therapy. These studies will demonstrate the translational potential of our compounds to investors and developers.

Identification of common pathogenic mechanisms driving squamous cell carcinomas of the anogenital tract and head&neck region to develop overarching therapeutic strategies 

• Research Director: Prof. Marisa Gariglio
• Line 3. Chronic Non-Communicable Diseases (NCDs) with a high impact on health and social care systems
• The two-year project has acquired funding of 269,080 euro.

The objective of the project is to study signalling pathways involved in the formation of squamous cell carcinomas (SCC), including the role of SIRT1 and TERT, and evaluate whether targeting them through gene modification is an effective strategy against these tumours. Squamous cell carcinomas of the anogenital tract and head and neck are influenced by aging, smoking, and HPV. While those related to smoking and aging show mutations in the PIK3CA and TP53 genes, along with TERT activation, those linked to HPV show inactivation of p53 and prb by the viral proteins E6 and E7.

Predicting multiple sclerosis disease activity and progression: development of a prognostic score and decisional support system. PROMISING study 

• Research Director: Sandra D’Alfonso 
• Line 3. Chronic Non-Communicable Diseases (NCDs) with a high impact on health and social care systems
• The two-year project has acquired funding of 189,390 euro

The PROMISING project focuses on creating a prognostic score for multiple sclerosis (MS), an autoimmune and neurodegenerative disease of the central nervous system. This score will be based on a series of predictors from genetics, epigenetics, environment, biomarkers and personal characteristics of the patients. The objective is to provide decision-making support to doctors and patients in the management of the disease, considering its course and the various genetic and environmental influences.

Constitutive activation of the CD49d/CD29 (VLA-4) integrin in chronic lymphocytic leukaemia: the other side of B-cell Receptor autonomous signalling

• Research Director: Gianluca Gaidano 
• Line 3. Chronic Non-Communicable Diseases (NCDs) with a high impact on health and social care systems
• The two-year project has acquired funding of 300,000 euro.

The project focuses on the effect of CD49d on micro-environmental interactions in chronic lymphocytic leukaemia (CLL), suggesting that B cell receptor (BCR) signals directly drive constitutive activation of VLA-4. We propose to analyse the levels of VLA-4 activation in patients with CLL, identifying the mechanisms responsible and correlating these levels with the clinical outcome, especially during treatment with ibrutinib. Using in vitro and murine models, we will try to clarify the correlation between VLA-4 activation and expression of specific BCR traits. The objective is to propose alternative therapeutic strategies to improve the treatment of CLL with high VLA-4 activation.

Calcineurin inhibition in astrocytes targeted by nanoparticles: a new therapeutic strategy to arrest Alzheimer’s disease progression

• Research Director: Lim Dmitry 
• Line 3. Chronic Non-Communicable Diseases (NCDs) with a high impact on health and social care systems
• The two-year project has acquired funding of 230,000 euro.

Alzheimer's disease (AD), which affects nearly 50 million people worldwide, continues to challenge current therapies, despite the Aß peptide having been identified as the primary cause. We therefore propose to examine a new possible therapy, focusing on calcineurin (CN), a protein that becomes hyperactive in AD, causing synaptic dysfunction and neuroinflammation. It is suggested that inhibition of CN with FK506 may reverse this dysfunction. We will explore the use of nanogels loaded with FK506 (FkNGs) to directly reach the brain to treat the disease. The objectives include evaluating the effects of AstroCN on neuronal damage and microglial activation, identifying the mechanisms through which its depletion could slow the disease, and validating the therapeutic efficacy of FkNGs in in vivo AD models. This approach will leverage a variety of AD models and innovative technologies to better understand the disease and develop new treatment options.

Discovery and validation of protein structural complexes in circulating biofluids as novel biomarkers for early diagnosis, prognosis and therapeutic management of patients affected by neurodegenerative disorders

• Research Director: Marcello Manfredi 
• Line 3. Chronic Non-Communicable Diseases (NCDs) with a high impact on health and social care systems
• The two-year project has acquired funding of 450,000 euro.

Neurodegenerative diseases (NDDs) such as Parkinson's disease (PD), Alzheimer's disease (AD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), involve the progressive dysfunction of distinct neuronal populations and share a common feature of accumulation of misfolded proteins. Despite considerable progress in research and treatment of NDDs, there is a lack of effective treatments and early diagnostic tools that can address these pathologies in the early stages of neurodegeneration. to use an innovative methodology based on size exclusion chromatography, mass spectrometry and bioinformatic analysis to map changes in protein complexes in biological fluids. The goal is to identify new biomarkers and pathogenetic hypotheses in NDDs and validate these biomarkers to improve early diagnosis and the study of the pathogenesis and progression of neurodegenerative diseases.