The study of human placental development has proven difficult, largely due to the inability of researchers to derive self-renewing trophoblast stem cells that retain the full differentiative potential of native placental trophoblast. Current studies are mostly done through mouse models or the culture of primary trophoblast cells. These methods of studying placental development are not ideal for understanding human placental development due to the differences between humans and mice and the limited proliferative and differentiative potential of available human primary trophoblast cells.

Histone 3 K27M mutated (H3K27M+) diffuse midline gliomas (DMGs) are a universally fatal pediatric brain cancer despite recently improved knowledge of the underlying biology. With relatively few advancements in treatment since targeted radiotherapy and a prognosis of generally less than one year to live, children diagnosed with DMGs are in great need of new therapeutic options. Chimeric antigen receptor (CAR) T cells have demonstrated remarkable clinical promise, particularly for blood cancers. To date, potency in solid tumors still remains limited.

Female cells undergo a naturally occurring mechanism to allow for dosage compensation, called X- chromosome Inactivation (XCI) so that X-linked genes are equally expressed in males. In this event, one of the two X chromosomes is randomly silenced due to XCI, which becomes transcriptionally inert. De novo variants in MECP2, a gene on the long arm of the X-chromosome, gives rise to Rett Syndrome (RTT) via a quasi-haploinsufficiency. RTT is a rare and progressive neurodevelopmental disorder that occurs predominantly in females.

The CRISPR-Cas9 system is a powerful tool that is revolutionizing how we understand and treat disease. Combining CRISPR-Cas9 genome editing with autologous stem cell transplantation has allowed the development of curative therapies for previously difficult-to-treat genetic diseases. In an effort to apply this technology to the treatment of an underrepresented disease, we set out to develop a novel CRISPR- Cas9-based therapy for the treatment of X-Linked Sideroblastic Anemia (XLSA). Patients with this disease develop red blood cells that fail to produce enough hemoglobin.