Institution: Ben-Gurion University of the Negev
Grant Type: Project Grant
Award Year: 2026–2029
Research Topics: Breast Cancer, Computational Biology, Drug Mechanisms and Development, Gastrointestinal Cancer, Men’s Cancers, Metastasis, Microenvironment, Ovarian and Uterine Cancer, Pancreatic Cancer, Prostate Cancer, Protein Engineering, Proteomics and Protein Structures, Women’s Cancers
As a molecular biologist focusing on protein engineering and cancer imaging and therapy, I joined the Ben-Gurion University (BGU) faculty in 2011, and my research focuses on understanding the underlying principles that shape target specificity in protein-protein interactions and the design of mono- and multi-specific high affinity inhibitors for structurally similar target proteins in cancer and other diseases. Since my recruitment to BGU, I was able to receive 30 competitive grants and awards including the ERC grant and the Krill Prize (Wolf Foundation). My research has resulted in over 86 papers and the presentation of my work at leading conferences.
About the Research
In the proposed study, we will use a combination of experimental multi-target selective library screening and in silico next generation sequencing analysis followed by state-of-the-art machine learning methodology and data normalization using purified proteins to develop a novel, single-step approach for comprehensively and quantitively mapping the specificity landscapes of interacting proteins – human trypsin-like proteases that promote cancer progression and their Kunitz-domain family inhibitors). For these protein-protein interactions, we will construct quantitative binding landscapes, thus, being able to accurately report binding affinity changes for tens of thousands of Kunitz-domain variants having single and, more importantly, multiple mutations, thus generating an unprecedented amount of mutational data that will then be used for designing new high-affinity and high-specificity protease inhibitors. We will next use these landscapes to generate mono- and bi-specific inhibitors to a single or multiple selected trypsin-like proteases and evaluate the ability of these engineered inhibitors to function as inhibitors for cancer progression, invasion and spread.
We envision that the protein inhibitors generated from these efforts will become eminently useful in the clinic as antimetastatic therapies and as molecular cancer imaging agents, targeted drug delivery agents, and selective tissue targeting probes.
