One-Two Punch Therapy for Refractory Cancer in Human and Canine
Therapy-induced senescence (TIS) creates relapse□competent tumor reservoirs that undermine durable responses to cancer treatments. Our objective is to turn this unavoidable liability into an actionable vulnerability using a sequenced “one□two punch”: induce TIS with clinically relevant chemotherapeutics, then clear the resulting senescent cancer cells with safer next□generation senolytics. We will characterize TIS states across prioritized cancer models, identify conserved vulnerabilities and biomarkers through transcriptomics and bioinformatics, and develop senolytics via high□content screening, medicinal chemistry, and ML/AI. This work will deliver an open TIS transcriptomic atlas and validated senogenic-senolytic combinations ready for future translational studies. The data generated here will support multiple competitive external grant applications to fund subsequent preclinical mouse studies and clinical comparative oncology pilots in pet dogs.
Team Lead
Lei Zhang
ljzhang@uga.edu
College of Pharmacy
Department of Pharmaceutical & Biomedical Sciences
Team Members
Eugene Douglass
Eugene.Douglass@uga.edu
College of Pharmacy
Department of Pharmaceutical & Biomedical Sciences
Khaled Rasheed
khaled@uga.edu
School of Computing
Institute for Artificial Intelligence
Jonathan Mochel
jpmochel@uga.edu
College of Veterinary Medicine
Department of Pathology, Precision One Health