Fernanda dos Reis Rocho postdoctoral scholarship hold.

Research Fernanda dos Reis Rocho

Research team

Expertise

My research expertise lies at the intersection of biochemistry and medicinal chemistry. I focus on the biochemical and biophysical characterization of small molecule inhibitors and single domain antibodies to address complex challenges in drug discovery. My research focuses on bridging the gap between in vitro assays and in vivo outcomes, enhancing the translatability of early-stage data into viable drug candidates.

Next-generation FAP tracers: single-domain antibody–FAPI conjugates for cancer theranostics (FAPIBODY). 01/08/2026 - 31/07/2028

Abstract

This proposal aims to create next-generation molecular imaging probes for cancer by targeting the fibroblast activation protein (FAP), a prominent biomarker of cancer-associated fibroblasts. FAP small-molecule inhibitors (FAPIs) have recently shown great promise for PET imaging, enabling sensitive visualization of tumors across multiple cancer types. However, despite their clinical impact, current FAPIs suffer from rapid systemic clearance and limited tumor retention, restricting their diagnostic sensitivity and therapeutic applicability. To address these shortcomings, this project introduces an innovative multivalent strategy that combines the potency of FAPIs with the specificity of single-domain antibodies (sdAbs). The proposal is structured around four main objectives: (1) systematic identification and characterization of sdAbs with strong affinity, high residence time, stability, and favorable biophysical properties; (2) chemical synthesis and optimization of sdAb–FAPI conjugates with tailored linkers to maximize stability and functionality; (3) structural and mechanistic validation of binding interactions using cryo-electron microscopy (cryo-EM), providing molecular-level insights for rational probe design; and (4) radiolabeling of the most promising conjugates and preclinical validation in PET/SPECT imaging to benchmark their performance against reference FAP tracers. By combining approaches from , chemical biology, structural biology, enzymology and radiopharmacy, the proposal will deliver innovative FAP-targeted probes with enhanced tumor retention, improved imaging quality, and expanded theranostic potential. These outcomes will not only advance cancer diagnostics but may also open new opportunities for treating diseases characterized by FAP expression.

Researcher(s)

Research team(s)

Funding

  • EU-KADER

Project type(s)

  • Research Project

Discovery of the first 'druglike' Granzyme B inhibitors, binding mode characterization and transformation into activity-based probes for Positron Emission Tomography (PET) Imaging. 01/01/2025 - 31/12/2026

Abstract

Granzyme B (GRZB) is the most abundant protease present in the granules of cytotoxic immune cells present and plays a key role in targeted cancer cell killing by the immune system. In tumors, the amount of GRZB that is secreted by activated immune cells, is inversely correlated with the degree of immunosuppression. Therefore, GRZB is quantified in tumor biopsies of patients treated with immune checkpoint inhibitors. Moreover, significant research effort is going to the discovery of Positron Emission Tomography (PET)-probes that allow minimally-invasive imaging of GRZB. This approach is also relevant for CAR T and CAR NK cell therapy, where the amount of released GRZB correlates with therapy response. Within a Marie Curie Doctoral Network 'OncoProTools' we are conducting research on novel GRZB activity-based probes. The recruited postdoc will contribute to this effort in the following ways: (i) Production and purification of GrzB via an in-house recombinant expression system; (ii) Structural biology: elucidation of the structure of 3 [GRZB-probe] co-complexes and determination of the probe binding modes via macromolecular X-ray crystallography; (iii) Kinetic characterization of the probes: determination of binding parameters via jump-dilution assays, progress curve analysis, eventually combined with grating-coupled interferometry; (iv) Synthesis of optimized probes: Preparation of further optimized GRZB probes.

Researcher(s)

Research team(s)

Funding

  • BOF

Project type(s)

  • Research Project