In the present PhD thesis mass-spectrometry-based approaches were used to identify putative biomarkers and therapeutic targets for uncurable rare diseases including Soft-tissue Sarcoma (STS), Mucosal melanoma (MM) and Amyotrophic lateral sclerosis (ALS). The present work allowed the identification of novel biological insights on these diseases. The thesis is divided into three main chapters. The first study focused on soft-tissue sarcoma. Our results provided new biological information on the biochemistry of sarcoma cancer and showed that proteomic analysis can be used to identify new druggable proteome. The main outcome of the research was the identification of three new drugs targeting sarcoma cancer in vitro and of many pathways and oncogenic proteins enriched in soft tissue sarcoma. In addition, mass-spectrometry based proteomics and lipidomics analysis of serum’s samples from STS patients allowed the identification of many potential biomarkers for the non-invasive and early diagnosis of the disease. In the second study, proteomic and bioinformatic approaches were used to investigate mucosal melanoma. Our results showed the alteration of several critical signalling pathways, including those controlling metastasis’ spread, cell cycle progression, immune reactions, oxidative stress responses, and cellular metabolism. Furthermore, the identification of the PI3K/Akt/mTOR pathway’s role opens new potential avenues for targeted therapies, with possible clinical applications. Lastly, the third study focused on neurodegenerative diseases and Amyotrophic lateral sclerosis (ALS). In this research, cerebral spinal fluid’s protein complexes from patients with ALS and controls were mapped. Our results showed the presence of altered complexes in ALS patients that could be used as biomarkers or therapeutic targets.

Novel mass-spectrometry approaches to decode molecular mechanisms and therapeutic targets in rare diseases: insights into soft-tissue sarcoma, mucosal melanoma and amyotrophic lateral sclerosis

DE GIORGIS, Veronica
2025

Abstract

In the present PhD thesis mass-spectrometry-based approaches were used to identify putative biomarkers and therapeutic targets for uncurable rare diseases including Soft-tissue Sarcoma (STS), Mucosal melanoma (MM) and Amyotrophic lateral sclerosis (ALS). The present work allowed the identification of novel biological insights on these diseases. The thesis is divided into three main chapters. The first study focused on soft-tissue sarcoma. Our results provided new biological information on the biochemistry of sarcoma cancer and showed that proteomic analysis can be used to identify new druggable proteome. The main outcome of the research was the identification of three new drugs targeting sarcoma cancer in vitro and of many pathways and oncogenic proteins enriched in soft tissue sarcoma. In addition, mass-spectrometry based proteomics and lipidomics analysis of serum’s samples from STS patients allowed the identification of many potential biomarkers for the non-invasive and early diagnosis of the disease. In the second study, proteomic and bioinformatic approaches were used to investigate mucosal melanoma. Our results showed the alteration of several critical signalling pathways, including those controlling metastasis’ spread, cell cycle progression, immune reactions, oxidative stress responses, and cellular metabolism. Furthermore, the identification of the PI3K/Akt/mTOR pathway’s role opens new potential avenues for targeted therapies, with possible clinical applications. Lastly, the third study focused on neurodegenerative diseases and Amyotrophic lateral sclerosis (ALS). In this research, cerebral spinal fluid’s protein complexes from patients with ALS and controls were mapped. Our results showed the presence of altered complexes in ALS patients that could be used as biomarkers or therapeutic targets.
2025
Inglese
MANFREDI, MARCELLO
Università degli Studi del Piemonte Orientale Amedeo Avogadro
Vercelli
223
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/218334
Il codice NBN di questa tesi è URN:NBN:IT:UNIUPO-218334