Kadriye Nehir Cosgun

During my Ph.D. at the Technical University of Dresden, I developed a novel humanized mouse model that supports stable engraftment of human hematopoietic stem cells and multilineage engraftment under physiological conditions (Cosgun et. al., Cell Stem Cell). This model established a more faithful platform for human hematopoiesis and hematologic disease, enabling new avenues for mechanistic and therapeutic discovery.

During my postdoctoral career at the University of California, San Francisco, City of Hope, and Yale University, I investigated signaling dependencies in hematologic malignancies. I discovered that hematopoietic cells have a unique dependence on intact β-catenin degradation machinery for survival (Cosgun et al., Nature Cancer). My work demonstrated that disrupting this pathway induces repressive β-catenin-Ikaros-NuRD complexes, suppresses MYC, and selectively eliminates leukemia cells, revealing an unexpected therapeutic vulnerability in B-cell acute lymphoblastic leukemia. In ongoing work, I have been using genome-wide CRISPR-Cas9 screening to uncover additional mechanisms regulating β-catenin stability and therapeutic response in treatment-resistant lymphoid malignancies.

Building on these discoveries, my ongoing research seeks to understand how signaling pathways function in a context-dependent manner across normal and malignant hematopoiesis. I am particularly interested in how genetic alterations, cellular state, and disease context shape signaling dependencies and create selective vulnerabilities across myeloid and lymphoid malignancies. By defining the mechanisms that determine why the same signaling pathway can have distinct effects across cellular and disease contexts, my research aims to identify therapeutic strategies that selectively target malignant cells while preserving normal hematopoiesis.