The behavior of all living cells is shaped by a complex interplay of intrinsic and extrinsic factors. Studies in human cells operate under the implicit assumption that they can generate views and insights reflective of cellular behavior in the body. However, most such studies still rely on model systems that, while helpful for exploring how aspects of cell biology vary with natural intrinsic diversity, are far removed from the metabolic conditions that cells may encounter in the human body. Moreover, such systems offer limited control of the extracellular environment. Therefore, it is a central challenge to investigate basic human cell physiology and drug sensitivity in systems that more closely model and address the possible impacts of cell-extrinsic factors.
The high-level goal of my research program is to understand how metabolic conditions affect the behavior of human cells, with an emphasis on unraveling genetic and environmental contributions to cell fitness. Several years ago, I created a new cell culture reagent designed to more faithfully reflect nutrient levels found in human blood: Human Plasma-Like Medium (HPLM), thus pioneering the systematic development and use of synthetic physiologic media. I will first discuss recent studies from our group that focused on understanding the basis for how gene essentiality and anticancer drug activity can be influenced by the nutrient environment. Additionally, my group has developed a new bioreactor platform that enables the continuous-flow culture of blood cells at metabolic steady state under tightly controlled growth conditions. I will also highlight examples of ongoing work that leverages this new platform to study cell behavior in steady state conditions with relevance to human health and disease.
