INTEGRATIVE GENOMICS UNVEILS TRANSCRIPTION FACTOR ROLES IN CELLULAR FATEAND SPATIALLY RESOLVED TRIPLE-NEGATIVE BREAST CANCER IMMUNITY CAPACITY

In this thesis, we explore integrative genomics through advanced sequencing to understand biological systems and processes, focusing on two main projects. The first investigates transcription factors (TFs) in cellular differentiation, addressing the inefficiency in current cellular conversion strategies due to the complex TF regulatory landscape. We developed a comprehensive screening of 130 developmental TFs, comparing their dosages in a single experiment to identify novel pioneer factors crucial for cellular identity. This approach aims to enhance our understanding of cell fate decisions. The second project examines triple-negative breast cancer (TNBC), characterized by its aggressiveness and treatment challenges due to tumor heterogeneity. We propose a novel clinical workflow combining spatial transcriptomics, RNA sequencing, and Immunohistochemistry to analyze TNBC, focusing on PD-L1 status. This method revealed sub-tumoral variations and identified LY6D as a new diagnostic marker, highlighting the potential of spatial transcriptomics in personalized medicine for TNBC. Overall, this dissertation contributes to the fields of cellular reprogramming and cancer diagnostics by integrating various genomic data and technologies to uncover complex molecular mechanisms and identify new therapeutic targets.

Grantor dc:publisher

Università degli Studi di Milano

Year dc:date

2024

Author dc:creator

• SLOVIN, SHAKED

Contributors dc:contributor

• supervisor: D. Cacchiarelli ; internal advisor: G. Gambardella ; external advisor: P. Carninci
• internal advisor: Gambardella
• Gennaro; external advisor: Carninci
• Piero; supervisor: Cacchiarelli
• Davide
• S. Slovin

• Computational biology
• Developmental biology
• Transcription Factors, Triple-Negative Breast Cancer, ATAC-seq, RNA-seq, Spatial Transcriptomics
• Settore BIO/11 - Biologia Molecolare

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

http://dx.doi.org/10.13130/slovin-shaked_phd2024-04-22
10.13130/slovin-shaked_phd2024-04-22

OAI identifier oai:identifier

oai:air.unimi.it:2434/1032276