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Breakthrough in cancer research: Nanobodies against CXCR4 and ACKR3

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26 November 2024
On Oct. 18, biotechnologist and pharmacologist Claudia Perez Almeria received her doctorate from VU University Amsterdam.

Dr. Perez Almeria's research focused on two membrane proteins that are overexpressed in cancer cells. Using nanobodies, she investigated their roles in cancer progression, aiming to uncover oncogenic signaling pathways and contribute to the development of more specific cancer therapies. This research was conducted within the Department of Chemistry and Pharmaceutical Sciences, in the Division of Medicinal Chemistry.

Cancer remains a significant global health challenge, with millions diagnosed annually and high mortality rates worldwide. Dr. Perez Almeria's work focused on the membrane proteins CXCR4 and ACKR3, which are implicated in cancer metastasis and tumor growth. By exploring the mechanisms these proteins use to drive oncogenic signaling, her research sought to advance the understanding of their functions and identify potential therapeutics.

 

Her approach combined innovative methods, including cell cultures, biochemical assays, and advanced fluorescence techniques, to monitor signaling pathway modulation in living cells in real-time. Nanobodies, which are single-domain antibody fragments with high specificity and affinity, were developed and evaluated for their potential to target cancers characterized by high expression of these CXCR4 and ACKR3proteins. Cutting-edge technologies like CRISPR knock-in (CRISPR-KI) and proteomics were used to analyze the interactome (protein-protein interactions) of these proteins, providing insights into their non-canonical functions.

 

Dr. Perez Almeria’s doctoral thesis, titled "Modulation of Non-Canonical CXCR4 and ACKR3 Functions" (accessible via this link), offers valuable contributions to understanding the role of these membrane proteins in cancer. Her findings aim to pave the way for the advancement of therapeutic strategies targeting CXCR4 and ACKR3 in cancer treatment.

 

Promotor Prof. Dr. Martine Smit, an expert in GPCR signaling and nanobody development, handed over the diploma after the defense and concluded the ceremony with a warm, funny and personal speech.

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