Ece Ozdemir Fajardo will be defending her thesis on December 5th. Please see the details below:
Time: Friday, December 5, 2025, 10AM
Location: Malone G33/35
Thesis Advisor: Kalina Hristova
Title: Quantitative Fluorescence Microscopy Method to Assess EGFR Activation, Heterointeractions, and Binding
Abstract: Receptor Tyrosine Kinases (RTKs) are key regulators of cellular growth, differentiation, and survival, and therefore serve as major therapeutic targets in cancer. However, the emergence of drug resistance continues to limit the long term efficacy of RTK directed therapies, highlighting the need for a deeper understanding of how these receptors are activated and modulated within the complex environment of the plasma membrane. Ligand bias, well established in other receptor families, represents an emerging regulatory mechanism in RTKs that can enable new therapeutic opportunities by revealing how distinct ligands differentially shape receptor activation and signaling.
In parallel, RTKs rarely function alone. Instead, they can exist in heterogeneous receptor complexes where heterointeractions between different RTKs can alter activation mechanisms, ligand binding affinities, and downstream signaling outcomes. Such interactions are of particular interest as dual specificity therapeutics, including bispecific antibodies, gain prominence in cancer treatment. Rational design of these agents requires quantitative insight into the nature, stability, and stoichiometry of RTK heterocomplexes.
This thesis focuses on developing and applying quantitative fluorescence-based approaches to investigate ligand dependent activation of EGFR and its modulation by heterointeractions. By characterizing how receptor partners influence ligand binding and activation, this work aims to provide a framework for understanding RTK signaling at the plasma membrane with greater mechanistic precision. The methodologies established here are broadly applicable to the study of any membrane receptor heterooligomer and to membrane protein interactions more generally, offering a foundation for future therapeutic innovation.