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Hinckley, J.

Publications and source records attributed to Hinckley, J..

2 recordsLinked to original sources

Accelerating Cell Culture Media Development Using Bayesian Optimization-Based Iterative Experimental Design

Optimizing operational conditions for complex biological systems used in life sciences research and biotechnology is an arduous task. Here, we have applied a Bayesian Optimization-based iterative framework for experimental design to accelerate cell culture media development for two applications. First, we show this approach yields new compositions of media with cytokine supplementation to maintain the viability and distribution of PBMCs in culture. Second, we applied this framework to optimize the production of three recombinant proteins in K.phaffii cultivations. For both applications, we identified conditions with improved outcomes compared to the initial standard media using 3 to 30 times fewer experiments than other methods such as the Design of Experiments. Subsequently, we also demonstrated the extensibility of our approach to efficiently account for additional design factors through transfer learning. These examples demonstrate how coupling data collection, modeling, and optimization in this iterative paradigm, while using an exploration-exploitation tradeoff in each iteration, can reduce the time and resources for these types of optimizations.

bioengineering↗

Metastasis-initiating osteosarcoma subpopulations establish paracrine interactions with both lung and tumor cells to create a metastatic niche

Osteosarcoma is an aggressive and deadly bone tumor, primarily afflicting children, adolescents, and young adults. Poor outcomes for osteosarcoma patients are intricately linked with the development of lung metastasis. While lung metastasis is responsible for nearly all deaths caused by osteosarcoma, identification of biologically defined, metastasis-targeting therapies remains elusive because the underlying cellular and molecular mechanisms that govern metastatic colonization of circulating tumor cells to the lung remains poorly understood. While thousands of tumor cells are released into circulation each day, very few can colonize the lung. Herein, using a combination of a novel organotypic metastasis in vitro model, single-cell RNA sequencing, human xenograft, and murine immunocompetent osteosarcoma models, we find that metastasis is initiated by a subpopulation of hypo-proliferative cells with the unique capacity to sustain production of metastasis promoting cytokines such as IL6 and CXCL8 in response to lung-epithelial derived IL1. Critically, genomic and pharmacologic disruption of IL1 signaling in osteosarcoma cells significantly reduces metastatic progression. Collectively, our study supports that tumor-stromal interactions are important for metastasis, and suggests that metastatic competency is driven, in part, by the tumor cells ability to respond to the metastatic niche. Our findings support that disruption of tumor-stromal signaling is a promising therapeutic approach to disrupt metastasis progression.

cancer biology↗