SC4: HOW TO BEST UTILIZE 3D CELLS, SPHEROIDS AND PDX MODELS IN ONCOLOGY
MONDAY, SEPTEMBER 16 | 2:00 - 5:00 PM
The course will provide an overview of 3D cell culture and spheroid models currently available and where and how these models are being used, specifically for oncology research. The instructors will share their experiences on how they tested and evaluated various cell culture reagents and growth matrices, what worked, what didn’t and what you need to consider when setting up low and high throughput screening experiments using 3D cell cultures in your lab. The challenges working with 3D cell cultures, from experimental design to data analysis will be discussed.
2:00 pm Welcome and Opening Remarks
2:10 Madhu Lal-Nag, PhD, Program Lead, Research Governance Council, Office of Translational Sciences, Center for Drug Evaluation & Research, U.S. Food and Drug Administration
- Advantage of 3D models over 2D models in cancer biology
- Basics of 3D culture: importance of cell line maintenance, culture medium and substratum
- Developing multicellular 3D models
- Evaluating models for high-throughput screens
- Types of assays, including CRISPR assays, we have used and are developing
3:10 Coffee Break
3:30 Geoffrey Bartholomeusz, PhD, Associate Professor and Director, Target Identification and Validation Program, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
- Developing multi-cellular 3D cell culture models for high throughput siRNA screening
- Specific 3D models for target identification and validation screens
- Challenges with high throughput screens utilizing 3D spheroid models
- Patient-derived xenograft ex vivo (PDXEx) models as a screening platform
- Future developments of 3D models for drug screens, co-culture 3D structures utilizing biopsy samples
4:30 Open Discussion and summary of key takeaways
5:00 pm Close of Short Course
Madhu Lal-Nag, PhD, Program Lead, Research Governance Council, Office of Translational Sciences, Center for Drug Evaluation & Research, U.S. Food and Drug Administration
Until recently Madhu Lal-Nag served as the head of the Trans NIH RNAi Facility at the National Center for Advancing Translational Sciences (NCATS) which is responsible for developing and conducting genome wide physiologically relevant phenotypic assays for Intramural researchers. Madhu joined NCATS in 2013, where she worked as a research scientist primarily to develop an assay platform of 3 Dimensional physiologically relevant, multi-cell-type disease models that are amenable to high-throughput screening. Prior to joining NCATS, she completed her postdoctoral fellowship at the National Institute on Aging. Her PhD is from the George Washington University in Molecular and Cellular Oncology. She has extensive experience in the miniaturization and optimization of physiologically relevant cell-based 2D and 3D assays to make them amenable for the screening of high-impact small molecule and functional genomics libraries with the goal of identifying unique receptor/ligand interaction and efficacy in various disease pathologies especially as they relate to the epigenetic modulation of cancer and stem cell biology.
Geoffrey Bartholomeusz, PhD, Associate Professor and Director, Target Identification and Validation Program, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Geoffrey Bartholomeusz has worked extensively as a cancer biologist with expertise in both molecular biology and drug development. A goal of his research is to utilize high throughput siRNA screens in a 3D cell culture assay to identify novel targets regulating the tumor architecture. His hypothesis driven study proposes that altering the tumor architecture will lower the levels of hypoxia within solid tumors sensitizing these tumors to irradiation and/or chemotherapy. In an attempt to confirm this hypothesis his team has developed a 3D spheroid cell culture model that has similarities to hypoxic regions of solid tumors. They have performed a high throughput siRNA screen and identified and validated potential targets whose silencing reduced the levels of hypoxia within the spheroid, and inhibited HIF1 activity. Studies are currently ongoing to confirm the hypothesis and test small molecules developed against these targets as potential anticancer agents. As a member of a multi-investigator group within MD Anderson Cancer Center Dr. Bartholomeusz is also involved in developing a technology that will permit them to regenerate tumors in the lab utilizing biopsy tissue with the goal of developing cancer patient specific drug cocktails.
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