Team Research

Cancer relapse after therapy remains a major clinical challenge. Most treatments fail to eradicate every malignant cell, leaving residual populations that drive recurrence. Growing evidence implicates therapy-induced senescence (TIS) as a key contributor: under chemotherapeutic stress, cancer cells can enter a senescent, “zombie-like” state marked by cell-cycle arrest, apoptosis resistance, a pro-inflammatory secretome, and blunted anti-tumor immunity. These cells reshape the tumor microenvironment, creating a permissive niche that fosters relapse and disease progression. 

Our consortium is developing senolytic agents that selectively eliminate senescent cells. We have identified a panel of promising candidates poised for translation. Instead of viewing TIS as solely a liability, we treat it as a therapeutic vulnerability to be induced and then exploited. We propose a “one-two punch” senogenic-senolytic strategy: 

• First punch: use standard chemotherapies to induce senescence and expose vulnerabilities in therapy-resistant cancer cells. 

• Second punch: deploy targeted senolytics to eradicate TIS reservoirs, preventing relapse and improving long-term outcomes. 

 We are assembling an interdisciplinary team at UGA spanning cancer and senescence biology, multi-omics, bioinformatics, drug screening and design, medicinal chemistry, AI/ML, systems pharmacology, animal models, and veterinary clinical trials in dogs with naturally occurring cancer. Our approach includes: 

• Multi-omics profiling (RNA-seq, proteomics, metabolomics) of human and canine cancer cell lines and organoids. 

• Integrated bioinformatics with human and veterinary tumor datasets to identify conserved, druggable senescence-linked vulnerabilities. 

• High-content screening with iterative medicinal chemistry to discover and optimize next-generation senolytics. 

• AI/ML frameworks to accelerate analysis of multi-omics data and guide compound prioritization. 

• 3D organoid and mouse models to capture and model tumor complexity and validate mechanisms. 

• Comparative oncology clinical trials in pet dogs to enable rapid, clinically relevant translation to human clinical trials. 

 This Pre-Seed award will catalyze collaboration across pharmacy, medicine, veterinary medicine, and computing at UGA. We will establish shared data resources and convene cross-college workshops, positioning the team for larger external support mechanisms (e.g., NIH R01s, Georgia CTSA, and comparative oncology trials). 

 Significance. Scientifically, this initiative aims to deliver a transformative strategy that reduces relapse and improves survival in both people and pets. Institutionally, it unifies complementary expertise, establishes durable infrastructure, and positions UGA at the forefront of senescence-targeted cancer therapeutics. 

Figure 1. Interdisciplinary collaboration is driving the development of “one-two punch” senogenic-senolytic therapies. Standard treatments first push cancer cells into a vulnerable senescent state. Next, senolytic drugs deliver the second punch by eliminating these “zombie-like” cells, aiming to prevent relapse and improve long-term outcomes for both human and veterinary patients. 

Team Lead

Zhang, Lei
ljzhang@uga.edu 
College: Pharmaceutical and Biomedical Sciences
Department: Department of Pharmaceutical and Biomedical Sciences (PBS)

Team Members

Douglass, Eugene
Eugene.Douglass@uga.edu
College: College of Pharmacy 
Department: Department of Pharmaceutical and Biomedical Sciences (PBS)

Rasheed, Khaled
khaled@uga.edu
College: School of Computing
Department: Department of Computer Science

Mochel, Jonathan
jpmochel@uga.edu
College: College of Veterinary Medicine
Department: Department of Pathology, Precision One Health

Jorn, Karin
Karin.Allenspach@uga.edu
College: College of Veterinary Medicine
Department: Department of Pathology

Zavros, Yana
Yana.Zavros@uga.edu
College: School of Medicine
Department: Department of Pathology

Xi, Yaguang
xi@uga.edu
College: College of Pharmacy
Department: Department of Interdisciplinary Biomedical Sciences (DIBS)

Huigens, Robert
Robert.huigens@uga.edu
College: College of Pharmacy
Department: Department of Pharmaceutical and Biomedical Sciences (PBS)

Crich, David
David.Crich@uga.edu
College: College of Pharmacy
Department: Department of Pharmaceutical and Biomedical Sciences (PBS)

Singh, Uma
ussingh@uga.edu
College: College of Pharmacy
Department: Department of Pharmaceutical and Biomedical Sciences (PBS)

Yi, Bin
Bin.Yi@uga.edu
College: College of Pharmacy
Department: Department of Pharmaceutical and Biomedical Sciences (PBS)