Identification of metabolic dysregulation and transcriptional networks in retinoblastoma reveals novel therapeutic targets: functional insights and novel therapeutic strategies using a correlative multi-omics approach

Vishnu Suresh Babu

Research output: ThesisDoctoral ThesisExternal prepared

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Abstract

Retinoblastoma (Rb) is a rare type of pediatric eye cancer that rapidly develops from the immature cells of the retina. This thesis discusses the pathogenesis and genetic changes in retinoblastoma and highlights the lack of disease-specific progression biomarkers. Furthermore, it reveals the significantly altered transcriptomic and metabolomic profiles of retinoblastoma tumors compared to healthy pediatric retinas. The metabolic vulnerability of Rb tumors is highlighted and HK1 is identified as a critical regulator of cellular bioenergetics and fuel utilization. Besides that, a novel energy-sensing network driven by HK1 and AMPKα in retinoblastoma cells is uncovered. EMT signatures and miRNA profiling in clinically advanced Rb tumors are revealed and the association of miR-181a-5p with a variety of distinct signaling pathways in Rb tumors is identified. Lastly, the thesis presents the potential use of cationic antimicrobial peptides (CAPs) as novel small drugs for retinoblastoma therapy.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Maastricht University
Supervisors/Advisors
  • Heymans, Stephane, Supervisor
  • Ghosh, Arkasubhra, Co-Supervisor, External person
Award date15 May 2023
Place of PublicationMaastricht
Publisher
Print ISBNs9789464693553
DOIs
Publication statusPublished - 2023

Keywords

  • retinoblastoma
  • metabolism
  • multi-omics
  • cancer research

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