Benjamin Lesch

Global blood shortages highlight the urgent need for scalable, lab-grown red blood cells. My research utilizes genome-wide CRISPR screens to uncover the genetic “rules” that control how human blood stem cells grow and mature into red blood cells. By systematically identifying the factors that drive massive cellular expansion and maturation, we aim to overcome current manufacturing bottlenecks and make large-scale, reliable lab-grown blood a reality for transfusion medicine.

Blood transfusions are critically important, yet our supply relies almost entirely on donor generosity, leaving it vulnerable to dangerous shortages. My research focuses on making scalable, lab-grown blood a reality by overcoming key bottlenecks in red blood cell manufacturing. To do this, I deploy genome-wide CRISPR screens in primary human blood stem cells to systematically turn genes off and observe how the developing red blood cells respond. This high-throughput approach allows me to map the genetic landscape of erythropoiesis and identify regulatory nodes that could be targeted to enhance cell expansion and maturation. Currently, a major hurdle in the field is generating sufficient yields of mature RBCs in vitro for clinical transfusion. Through preliminary validation of top screen hits, I have identified candidate targets capable of inducing up to 20-fold greater expansion of erythroid cells, as well as others that enforce erythroid lineage commitment. Crucially, this work has also revealed an inherent biological tradeoff between proliferation and terminal maturation. Future work will focus on harnessing these genetic levers to engineer an optimized, scalable manufacturing pipeline.