We are looking for individuals from diverse backgrounds to join our team.
We are looking for individuals from diverse backgrounds to join our team.
Engineering the placenta-uterine interface with stem cells
Complications in placental development are the leading cause of adverse pregnancy outcomes, causing preeclampsia, fetal growth restrictions, recurrent miscarriages, and many other obstetric disorders, contributing significantly to maternal and fetal morbidity and mortality. They are most commonly caused by a misregulation of placenta formation at the beginning of pregnancy and by inadequate interactions between the placenta cells and the uterus. We employ tissue engineering, CRISPR screens, and machine learning to provide critical insights into the genetic and signaling mechanisms underlying placenta-uterine crosstalk, in healthy and pathological settings.
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​​Implications to human health: Improper placenta development is the most important bottleneck of pregnancy whose failure is the leading cause of infertility, recurrent pregnancy loss, pre-eclampsia, and many other early pregnancy disorders. Elucidating the molecular causes of placenta development will help devise new early diagnostic and therapeutic strategies aimed at improving reproductive health.
New paradigms in human organoids
Mapping the detailed genomic and epigenomic networks that drive human organogenesis is one of the most desired goals of contemporary biology. It will not only allow us to build in vitro models of disease, but one day open doors to growing on-demand and patient-specific organs in a lab. In fact, we are getting very close to this goal. With the recent explosive progress in stem cell biology, we can now create the miniature and abstract versions of human organs, called organoids, by growing pluripotent stem cells in three-dimensional matrices and exposing them to specific chemical signals. However, despite the cellular diversity of these tissues, organoids are still far from human organs. Furthermore, the vast majority of organoid research is focussed on the brain or the intestine, perhaps because these organs form at the extreme ends of the body, thus requiring somewhat more easily employable signaling requirements, high or no signaling.
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We recognize two key challenges in the field of synthetic organogenesis. The first is correctly patterning organoids to recreate more accurately the spatial signaling hierarchy in organogenesis. The second is engineering pure regionally specialized tissues such that can be used in regenerative medicine. To address these challenges, we employ a combination of tissue engineering and CRISPR gene editing to create the realistic organ-forming signaling gradients and to control precisely the genetic circuitry that instructs cell identity and location within an organ. Our goal is to generate organoids that can recreate organogenesis along portions or entire body axes, revealing clues of how individual organs are specified and spatially segregated, and to map out the single cell atlas of early human organogenesis.
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Implications to human health: Developing tools that more accurately differentiate pluripotent stem cells into patterned organ progenitors will create opportunities for using organoids as a renewable patient-specific source of human tissues. Research that aims to bridge the gap between organoids and human organogenesis should be prioritized to advance the potential for regenerative and transplant medicine.
Placenta development across mammals
Signaling pathways that transform the early embryo into defined body plans are remarkably conserved across the animal kingdom. Yet, we always develop into completely differently looking organisms. A human always looks like a human, a mouse always looks like a mouse, and no mouse embryo ever develops into an elephant. It is becoming increasingly clear that beyond a genetic code, there are external cues that influence the way signals interact with the cells and in this way control cell specialization and tissue patterning. We reconstitute early embryonic patterning from stem cells and employ materials with controlled chemical and mechanical properties, single cell profiling, and CRISPR gene editing, to map out the detailed hierarchies in cell fate decisions from early embryo to its organ progenitors. We also investigate the influence of external factors on these decisions, ultimately to figure out how the embryo attains its unique shape.