Introducing a ‘Phase 0’ in Clinical Trials with Precise Organoid-based Disease Models Webinar
October 17, 2024, at 12:00 PM ETAbstract
To improve precision in disease modeling, the HUMANOIDTM Center of Research Excellence (CoRE) uses precise computational tools to rigorously vet organoid models. In this webinar, we highlight the combined use of ATCC’s colorectal cancer (CRCs) organoids with an unbiased network-based approach to track, differentiate, and selectively target cancer stem cells (CSCs). We built a transcriptomic network to identify therapeutic perturbations that can reinstate the expression of CDX2, a transcription factor whose loss identifies poorly differentiated (CSC-enriched) CRCs and whose reinstatement is predicted to reduce the risk of death/relapse by 50%. Here, the top candidate target predictably shifts the network, induces CDX2 and crypt differentiation, and shows selective cytotoxicity towards CDX2-negative models. A 50-gene signature of therapeutic response shows that CDX2-reinstatement therapy is expected to translate into a ∼50% reduction in the risk of mortality/recurrence. These results indicate that CDX2-reinstatement selectively triggers differentiation and death of colorectal CSCs, thereby demonstrating that our network-guided approach identifies a first-in-class differentiation therapy agent in solid tumors.
Key takeaways
- We use human-derived organoid models that retain both the genetic and epigenetic aspects of the diseased cell states.
- This ‘Phase 0’ approach is designed to improve both precision and personalization, thereby closing the translational gap in modern medicine.
Presenter
Courtney Tindle, MS
Director and Program Manager at HUMANOIDTM CoRE
Courtney Tindle has a Master of Science (MS) degree in Biology and currently serves as the Director and Program Manager at HUMANOIDTM CoRE. HUMANOID’s area of expertise is in disease modeling with multi-dimensional organoids. These models are computationally vetted for their similarity to human disease and are designed to serve as dynamic platforms for use in semi/high-throughput therapeutic screening for efficacy and toxicity, inspiring the concept of Phase ‘0’ clinical trials. Courtney is a proud first-generation college graduate and received her bachelor’s and master’s degrees at UCSD. During her MS, she studied the clearance of Salmonella in murine macrophages via the autophagy pathway. After graduating, she explored opportunities for academic mentoring and teaching at the community college level. Therein, she taught Introductory Biology and Paramedical Microbiology for 3 years. Subsequently, in June of 2019, she transitioned back into research and assumed the role of a staff scientist at UC San Diego’s HUMANOIDTM [HUMANOID Center of Research Excellence]. Within the next 2 years, she rose through the ranks to Staff Director and now Director and Program Manager of the organization. She leads multiple academic and industry projects with a team of ~4-6 scientists.